Association of Prior BNT162b2 COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection in Children and Adolescents During Omicron Predominance

Authors: Katherine E. Fleming-Dutra, MD1Amadea Britton, MD1,2Nong Shang, PhD1et al May 13, 2022 JAMA. Published online May 13, 2022. doi:10.1001/jama.2022.7493

Key Points

Question  Does the estimated effectiveness of 2 doses of the BNT162b2 COVID-19 vaccine against symptomatic SARS-CoV-2 Omicron variant infection (based on the odds ratio for the association of prior vaccination and infection) wane rapidly among children and adolescents, as has been observed for adults?

Findings  In a test-negative, case-control study conducted from December 2021 to February 2022 during Omicron variant predominance that included 121 952 tests from sites across the US, estimated vaccine effectiveness against symptomatic infection for children 5 to 11 years of age was 60.1% 2 to 4 weeks after dose 2 and 28.9% during month 2 after dose 2. Among adolescents 12 to 15 years of age, estimated vaccine effectiveness was 59.5% 2 to 4 weeks after dose 2 and 16.6% during month 2; estimated booster dose effectiveness in adolescents 2 to 6.5 weeks after the booster was 71.1%.

Meaning  Among children and adolescents, estimated vaccine effectiveness for 2 doses of BNT162b2 against symptomatic infection decreased rapidly, and among adolescents increased after a booster dose.Abstract

Importance  Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster.

Objective  To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance.

Design, Setting, and Participants  A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19–like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022.

Exposures  Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose).

Main Outcomes and Measures  Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 − OR) × 100%.

Results  A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).

Conclusions and Relevance  Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.Introduction

In December 2021 and January 2022, the spread of the SARS-CoV-2 Omicron variant led to the highest rates of COVID-19 cases among children 5 to 15 years old1 and the highest rate of pediatric hospitalizations (age ≤17 years) with COVID-19 to this point in the pandemic.2,3 Randomized trials of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech), the only COVID-19 vaccine authorized for use in children and adolescents 5 to 15 years of age, were conducted before the emergence of the Omicron variant and demonstrated high efficacy of 2 doses against COVID-19 (100% and 91% among those aged 12-15 and 5-11 years, respectively).4,5 The US Food and Drug Administration issued Emergency Use Authorization for BNT162b2 (2 doses of 30 μg) for those aged 12 to 15 years on May 10, 2021,6 and for those aged 5 to 11 years (2 doses of 10 μg) on October 29, 2021.7 Evidence that estimated vaccine effectiveness (VE) waned over time among adults and adolescents8 contributed to a recommendation on January 5, 2022, for a booster (30-μg dose) 5 months or more after the second dose for adolescents 12 to 15 years old.9

Observational studies in adults documented lower protection from mRNA vaccines against the Omicron variant compared with the Delta variant and rapid waning of protection.10,11 However, observational estimates of VE among children 5 to 11 years old and adolescents 12 to 15 years old during Omicron variant predominance are lacking but needed to inform COVID-19 vaccine policy and use of nonpharmaceutical interventions in these age groups. The objectives of this analysis were to use the odds ratio (OR) for the association of prior vaccination and symptomatic infection to estimate BNT162b2 VE during Omicron variant predominance of (1) 2 doses among children 5 to 11 years old and adolescents 12 to 15 years old over time since the second dose and (2) 3 doses among adolescents 12 to 15 years old.Methods

This activity was determined to be public health surveillance as defined in 45 CFR §46.102(l) (US Department of Health and Human Services [HHS], Title 45 Code of Federal Regulations, §46 Protection of Human Subjects); thus, it was not submitted for institutional review board approval and informed consent was not needed.Data Source

Data from the Increasing Community Access to Testing (ICATT) platform were used. ICATT is an HHS program that contracts with 4 commercial pharmacy chains to facilitate drive-through SARS-CoV-2 testing nationally.8,10,12,13 No-cost testing is available to anyone regardless of symptom or exposure status, and sites were selected to address COVID-19 health disparities by increasing access in racially and ethnically diverse communities and areas with moderate to high social vulnerability based on the Social Vulnerability Index (SVI).14 During the analysis period, contracted pharmacy chains used different versions of the registration questionnaire and not all captured data on booster doses. This analysis was, therefore, limited to a single chain, which collected data on booster doses and provided 82% of tests platform-wide for children and adolescents aged 5 to 15 years during the analysis period.

When registering for SARS-CoV-2 testing, individuals or parents/guardians of minors answered a questionnaire (available in English or Spanish) to self-report demographic information (including race and ethnicity selected from fixed categories, shown in the Table), COVID-19–like illness symptoms (fever, cough, shortness of breath, recent loss of sense of smell or taste, muscle pain, fatigue, chill, headache, sore throat, congestion or runny nose, vomiting, or diarrhea; reported to HHS as asymptomatic or symptomatic with ≥1 symptom), and vaccination status.10 Race and ethnicity were collected as part of the HHS COVID-19 laboratory reporting requirements.15 Self-reported COVID-19 vaccination data included number of doses received up to 4, and for each dose, vaccine product and month and year received. For doses reported in the same month or the month before test registration, the registrant was asked whether the most recent dose was administered at least 2 weeks before the test date. Reporting of vaccination status was neither mandatory nor verified. Test registrants were also asked to self-report underlying health conditions, including immunocompromising conditions (defined in the questionnaire as “immunocompromising medications, solid organ or blood stem cell transplant, HIV, or other immunocompromising conditions”), and whether they had previously tested positive for SARS-CoV-2 (within 90 days and/or >90 days before test registration); answers were not verified.

Nasal swabs were self-collected at drive-through sites and tested for SARS-CoV-2 either onsite with the ID Now (Abbott Diagnostics Scarborough Inc) rapid nucleic acid amplification test (NAAT) or at contracted laboratories using laboratory-based NAAT (TaqPath COVID-19 Combo Kit [Thermo Fischer Scientific Inc] or COVID-19 RT-PCR Test [Laboratory Corporation of America]). Deidentified questionnaire data, specimen collection date, test type, test result, and testing site location and census tract SVI14 were reported to HHS with an approximate 3-day lag.Study Design

A test-negative, case-control analysis16 was conducted to estimate BNT162b2 VE against symptomatic infection. This analysis used rapid and laboratory-based NAATs from children and adolescents aged 5 to 15 years reporting 1 or more symptoms tested at the pharmacy chain from December 26, 2021, to February 21, 2022 (data downloaded February 22, 2022). The unit of analysis was tests, because unique identifiers for individuals were not available. Cases were defined as those with positive SARS-CoV-2 NAAT results, and controls were those with negative NAAT results. Tests from children and adolescents meeting any of the following criteria were excluded: indeterminate test results, missing assay type, reported an immunocompromising condition (because COVID-19 vaccine recommendations differ for these individuals),9 unknown vaccination status, vaccine product other than BNT162b2, receipt of 1 vaccine dose or receipt of the second or third dose within 2 weeks of the test date, vaccination before the month of the recommendation by the Advisory Committee on Immunization Practices (for children 5-11 years, November 2021; for adolescents 12-15 years, May 2021 for the primary series and January 2022 for the booster dose),9,17,18 receipt of more than the authorized number of doses for nonimmunocompromised individuals (>2 for children 5-11 years, >3 for adolescents 12-15 years), receipt of a third dose less than 4 months after the second dose (for adolescents 12-15 years),9 or inconsistent vaccination information (eg, reported vaccine receipt but missing dose dates, reported no vaccine receipt but doses reported).Exposure

The exposures of interest were 2 BNT162b2 doses for children 5 to 11 years old and 2 or 3 BNT162b2 doses for adolescents 12 to 15 years old. Cases and controls were considered unvaccinated if tests were from children and adolescents who received no COVID-19 vaccine before the SARS-CoV-2 test. Cases and controls were considered vaccinated with 2 or 3 doses if tests were from children and adolescents who reported receiving the second or third dose 2 weeks or more before their SARS-CoV-2 test.Outcome

The outcome measure was symptomatic SARS-CoV-2 infection determined by positive NAAT result in a person reporting COVID-19–like illness.Statistical Analysis

Associations between symptomatic SARS-CoV-2 infection and BNT162b2 vaccination were estimated by comparing the odds of prior vaccination with 2 or 3 doses (exposed) vs no vaccination (unexposed) in cases vs controls using multivariable logistic regression. The OR was used to estimate VE, where VE = (1 – OR) × 100%. Logistic regression models were adjusted for calendar day of test (continuous variable), race, ethnicity, sex, testing site region, and testing site census tract SVI (continuous variable).14 Tests with missing sex and site census tract SVI were not included in adjusted analyses. Unknown race and ethnicity were coded as categorical levels within each variable to retain those tests in regression models.

Adjusted OR and corresponding VE of 2 doses were estimated by age group (5-11 years and 12-15 years) and month since the second dose. Because only vaccination month and year but not exact calendar dates of each dose were reported, month since the second dose was calculated as the difference between the month and year of testing and the month and year of the second vaccine dose (at least 2 weeks after the second dose). The range of possible days after the second dose for month 0 was 14 to 30 days; month 1, 14 to 60 days; month 2, 30 to 90 days; month 3, 60 to 120 days, and so on (assuming 30 days per month). Because of potential imprecision of month since vaccination based on calendar month of vaccination and testing rather than exact dates, a simulation analysis (of scenarios with rapid vs slow vaccine uptake and varying date of vaccine introduction) and an analysis of previously published data from this platform8 were conducted to compare VE estimates using this approach with those with exact number of days since the second dose (eAppendix in the Supplement).

The maximum difference between calendar month of SARS-CoV-2 test and calendar month of the second dose was 3 months for children 5 to 11 years old (tested during February 2022 and second dose received in November 2021) and 9 months for adolescents 12 to 15 years old (tested during February 2022 and second dose received in May 2021). However, VE was not calculated for the last month since the second dose (month 3 for children and month 9 for adolescents) because the number of possible days since the second dose was limited in the last month. This was a result of both the timing of vaccine authorization (children became eligible for second doses in late November 202118 and adolescents in late May 202117) and by the timing of the end of the study period (test dates were only included through February 21, 2022) (eAppendix in the Supplement). For adolescents 12 to 15 years of age, the maximum possible time after a booster was 6.5 weeks (tested February 21, 2022, and booster dose received after recommendation by the Advisory Committee on Immunization Practices on January 5, 2022).9

To assess the effect of reported prior SARS-CoV-2 infection on estimated 2-dose VE (by age group and month since the second dose), 3 sensitivity analyses were conducted. The first analysis included only tests from individuals without any reported prior SARS-CoV-2–positive test result. The second analysis included only tests from individuals without reported prior SARS-CoV-2–positive test result within 90 days, because a recent prior positive test result could have been due to prolonged NAAT positivity,19 multiple tests within the same illness episode (eg, confirming an at-home test), or reinfection with a different variant in the setting of Omicron variant emergence. The third analysis included only tests from individuals without reported prior SARS-CoV-2–positive test result more than 90 days prior to the test date, because prior SARS-CoV-2 infection provides infection-induced immunity in both vaccinated and unvaccinated individuals.20

The adjusted OR and corresponding VE of 3 doses among adolescents 12 to 15 years old were estimated overall (ie, not by month since the second dose) due to the short timeframe (6.5 weeks) since booster recommendation.

Statistical analyses were performed in R (version 4.1.2; R Foundation) and SAS (version 9.4; SAS Institute Inc). OR and VE estimates were presented with 95% CIs. To compare the waning pattern for estimated VE since the second dose between children and adolescents, an interaction term between age group (5-11 vs 12-15 years) and month after the second dose (for months 0, 1, and 2) was added to the model; a likelihood ratio test comparing the models with and without the interaction term was used to evaluate the interaction. Two-sided P values comparing the magnitude of the association of vaccination and infection between the 2 age groups and across study months were estimated; a P value less than .05 was considered significant. Because of the potential for type I error due to multiple comparisons, findings should be interpreted as exploratory.Results

A total of 121 952 tests from children and adolescents aged 5 to 15 years at 6897 sites across 49 states (all states except North Dakota), Washington, DC, and Puerto Rico, met inclusion criteria (Figure 1), including 53 272 cases (43.7%) and 68 680 controls (56.3%). The median age among individuals with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. Among 74 208 included tests from children 5 to 11 years old, 58 430 (78.4%) were from unvaccinated children and 15 778 (21.3%) from those vaccinated with 2 doses. Among 47 744 included tests from adolescents 12 to 15 years old, 24 767 (51.9%) were from unvaccinated adolescents, 22 072 (46.2%) from those vaccinated with 2 doses, and 905 (1.9%) from those with booster doses.

Included tests were more frequently rapid NAAT (66.3%) than laboratory-based NAAT (33.7%), and controls were more often tested by rapid NAAT than cases (70.5% vs 60.2% for children; 71.5% vs 60.8% for adolescents) (Table). Cases vs controls were more often tests from persons from the South Atlantic region (27.6% vs 22.3% for children; 27.9% vs 23.7% for adolescents). Report of prior positive SARS-CoV-2 test result within 90 days of the test date was more common among cases than controls (22.0% vs 13.0% for children; 21.1% vs 15.5% for adolescents), while report of a positive test result more than 90 days before the test date was less common among cases than controls (4.9% vs 11.1% for children; 6.5% vs 13.4% for adolescents).

Among children 5 to 11 years old, the adjusted OR for symptomatic infection for tests performed during month 0 after the second dose was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and during month 2 after the second dose was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) (Figure 2). For adolescents 12 to 15 years old, the adjusted OR during month 0 after the second dose was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]), during month 2 after the second dose was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]), and was no longer significantly different from 0 during month 3 after the second dose (OR, 0.90 [95% CI, 0.82-1.00]; estimated VE, 9.6% [95% CI, −0.1% to 18.3%]). Estimated VE was not significantly different between children and adolescents during months 0 and 1 after the second dose, but estimated VE in children was significantly higher than in adolescents during month 2 (P value for month 0: .99; month 1: .40; month 2: .01; and for months 0-2 combined: .06).

The simulation analysis showed that estimated VE waning curves that used either the exact number of days or calculated months since the second dose were in close agreement in scenarios with rapid and slow vaccine uptake and vaccine introduction on day 1 and day 16 of month 0 (eFigures 1-2 in the Supplement). The analysis of previously published data from this platform showed estimated monthly VE waning curves aligned well with daily VE waning curves (eFigures 3-4 in the Supplement).

Sensitivity analyses limited to those without any prior SARS-CoV-2–positive test result (eFigure 5 in the Supplement), without prior SARS-CoV-2–positive test result within 90 days of test date (eFigure 6 in the Supplement), and without prior SARS-CoV-2–positive test result more than 90 days prior to test date (eFigure 7 in the Supplement) yielded estimated VE at month 0 of 60.4% to 66.4% among children 5 to 11 years old and 58.3% to 64.3% among adolescents 12 to 15 years old. These were similar to the main analysis results that did not take prior infection into account. However, estimated VE in the sensitivity analyses was somewhat more sustained over time relative to the main analysis, particularly for the model limited to tests from individuals without any reported prior infection (estimated VE among children was 39.8% during month 2; among adolescents, estimated VE was significantly different from 0 until month 7) and the model limited to tests from those without infection within 90 days (estimated VE among children was 39.8% at month 2; among adolescents, estimated VE was significantly different from 0 until month 5).

Among adolescents, the adjusted OR for a booster dose 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%]).Discussion

This analysis estimated BNT162b2 VE among children 5 to 11 years old and adolescents 12 to 15 years old with COVID-19–like illness tested for SARS-CoV-2 using NAAT at drive-through US pharmacy sites from December 26, 2021, to February 21, 2022. It found the estimated VE of the BNT162b2 2-dose primary series against symptomatic infection with the Omicron variant was modest and decreased over time since vaccination in both age groups, similar to the pattern observed in adults during Omicron variant predominance.10 A booster dose was associated with increased protection against symptomatic infection in adolescents.

Previous analyses among adults have shown lower estimated VE against the Omicron variant than against the Delta variant and waning of mRNA vaccine protection against symptomatic infection, regardless of predominant variant.8,10,11 A recent analysis from the same testing platform as this analysis demonstrated the estimated VE of the 2-dose BNT162b2 primary series against symptomatic Omicron infection among adults 18 years or older was 42% at 2 to 4 weeks after the second dose. This decreased to not significantly different from 0 by 3 months after the second dose.10 In this analysis, the estimated VE against symptomatic infection among adolescents 12 to 15 years old also was not significantly different from 0 during month 3 after the second dose. Among children 5 to 11 years old, the duration of protection could only be assessed up through month 2 since the second dose, and continued monitoring will be important.

Among adolescents 12 to 15 years old, the estimated VE against symptomatic infection increased after a booster dose. This finding is consistent with data on adults from this platform and from other studies among adults and adolescents during Omicron variant predominance, which provide evidence of increased protection following mRNA vaccine booster dose.10,21,22 Given the well-established pattern of waning mRNA VE after 2 doses and early evidence of waning of booster dose protection in adults,22 monitoring the duration of protection from booster doses in adolescents will be important. Booster doses may be needed to optimize protection against symptomatic infection with the Omicron variant in children 5 to 11 years old as well.

Children aged 5 to 11 years receive a lower-dose formulation (10 μg) of BNT162b2 than adolescents and adults (30 μg), and limited observational data are available on VE with the 10-μg dose. In this analysis, the similar starting VE among children and adolescents and slower waning seen in children than adolescents suggest the 10-μg dose performed as well or better in children than the 30-μg dose in adolescents. These findings are consistent with the phase 2-3 trial in which immunogenicity of the 10-μg dose among children 5 to 11 years old, as measured by geometric mean titers of neutralizing antibodies 1 month after the second dose, was not significantly different from that generated by 30 μg in persons 16 to 25 years old.4 Furthermore, recent studies indicate estimated 2-dose BNT162b2 VE is similar among children 5 to 11 years old and adolescents 12 to 15 years old against any Omicron infection with or without symptoms (31% and 59%, respectively, with overlapping CIs)23 and against emergency department and urgent care visits due to COVID-19 (51% among children 5-11 years vs 45% among adolescents 12-15 years, with overlapping CIs).21

Prior SARS-CoV-2 infection may influence estimated VE in various ways. Unvaccinated persons with prior infection may have infection-induced immunity, which could bias VE estimates toward the null, whereas vaccinated persons with prior infection may have higher levels of protection than those with vaccination alone.20 Additionally, the proportion of the population with prior infection and how protective prior infection from a previous variant is against currently circulating variants can also influence estimated VE. The sensitivity analysis including only children and adolescents without any reported prior infection showed that waning of estimated VE was less pronounced than in the main analysis, which may provide the clearest picture of protection provided by vaccination. However, prior SARS-CoV-2 infection is increasingly common; the estimated SARS-CoV-2 infection–induced antibody seroprevalence among US children 0 to 17 years old who had blood specimens tested at commercial laboratories (for reasons unrelated to COVID-19) was 45% in December 2021.24 Although history of SARS-CoV-2 infection was self-reported in this analysis and is an imperfect measure, 27% of tests were from persons reporting prior infection. Thus, inclusion of tests from persons with prior infection may more accurately reflect vaccine performance under current conditions in the US.

Although estimated VE against symptomatic infection waned quickly in this analysis, vaccine protection against symptomatic infection is harder to achieve than protection against severe disease. For mRNA vaccines including BNT162b2, estimated VE against severe disease and hospitalization has been higher and waned more slowly than estimated VE against infection among adolescents and adults during Delta predominance25 and Omicron predominance.21,22 While estimated VE against symptomatic infection is an important end point to inform nonpharmaceutical intervention policy decisions and can provide an early warning signal of declining VE, estimated VE against severe disease is needed for children and adolescents during Omicron variant predominance.Limitations

This analysis is subject to several limitations. First, vaccination status was self-reported, which may lead to misclassification. Second, approximately 12% of tests were from people who did not report vaccination status, and 8% had missing symptom data. Exclusion of these tests may have biased results. Third, vaccination dose dates were provided as month and year rather than exact calendar date, which could affect the estimated VE over time through imprecise classification of months since vaccination. A simulation analysis and an analysis of previously published data from this platform8 (eAppendix in the Supplement) suggested that the magnitude and patterns of estimated VE over time would be similar when estimated by day or month since second dose and additionally would be robust to different speeds of vaccine uptake and timing of vaccine authorization.

Fourth, person-level identifiers were not available; therefore, the unit of analysis was tests, not individuals. The analysis was restricted to symptomatic children and adolescents tested within a 2-month timeframe, likely reducing the number of individuals contributing multiple tests. Fifth, these data are from children and adolescents who sought testing at ICATT sites and may not be generalizable to the US population. Nonetheless, these data represent a large sample of children and adolescents 5 to 15 years old tested at 6897 sites nationally. Sixth, primary series vaccine coverage among children 5 to 11 years old and booster coverage among adolescents 12 to 15 years old remained low in the US during the time of this study.26 Children who received the primary series and boosted adolescents may differ in meaningful and unmeasured ways from unvaccinated children and unboosted adolescents.

Seventh, due to the short time (6.5 weeks) since adolescents 12 to 15 years old were recommended for a booster dose, this analysis was unable to estimate booster VE over time in adolescents. Eighth, this analysis includes both rapid and laboratory-based NAAT. While there may be slight variation in the sensitivity of assays performed at different laboratories, NAAT, including rapid NAAT, is the most sensitive method available for detection of SARS-CoV-2 infection.27 Simulations of the effect of test sensitivity on influenza VE estimates using the test-negative design suggest that estimated VE remains relatively stable over a range of test sensitivity from 80% to 100%.28Conclusions

Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.

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20.Hall  V, Foulkes  S, Insalata  F,  et al; SIREN Study Group.  Protection against SARS-CoV-2 after COVID-19 vaccination and previous infection.   N Engl J Med. 2022;386(13):1207-1220. doi:10.1056/NEJMoa2118691PubMedGoogle ScholarCrossref

21.Klein  NP, Stockwell  MS, Demarco  M,  et al.  Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA vaccination in preventing COVID-19-associated emergency department and urgent care encounters and hospitalizations among nonimmunocompromised children and adolescents aged 5-17 years: VISION Network, 10 states, April 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(9):352-358. doi:10.15585/mmwr.mm7109e3PubMedGoogle ScholarCrossref

22.Ferdinands  JM, Rao  S, Dixon  BE,  et al.  Waning 2-dose and 3-dose effectiveness of mRNA vaccines against COVID-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance: VISION Network, 10 states, August 2021-January 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(7):255-263. doi:10.15585/mmwr.mm7107e2PubMedGoogle ScholarCrossref

23.Fowlkes  AL, Yoon  SK, Lutrick  K,  et al.  Effectiveness of 2-dose BNT162b2 (Pfizer BioNTech) mRNA vaccine in preventing SARS-CoV-2 infection among children aged 5-11 years and adolescents aged 12-15 years: PROTECT cohort, July 2021-February 2022.   MMWR Morb Mortal Wkly Rep. 2022;71(11):422-428. doi:10.15585/mmwr.mm7111e1PubMedGoogle ScholarCrossref

24.Centers for Disease Control and Prevention. COVID data tracker: nationwide COVID-19 infection-induced antibody seroprevalence (commercial laboratories). Accessed March 9, 2022. https://covid.cdc.gov/covid-data-tracker/#national-lab

25.Tartof  SY, Slezak  JM, Fischer  H,  et al.  Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study.   Lancet. 2021;398(10309):1407-1416. doi:10.1016/S0140-6736(21)02183-8PubMedGoogle ScholarCrossref

26.Centers for Disease Control and Prevention. COVID data tracker: trends in demographic characteristics of people receiving COVID-19 vaccinations in the United States. Accessed February 13, 2022. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends

27.Food and Drug Administration. In vitro diagnostics EUAs: molecular diagnostic tests for SARS-CoV-2. Accessed March 17, 2022. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-molecular-diagnostic-tests-sars-cov-22

8.Jackson  ML, Rothman  KJ.  Effects of imperfect test sensitivity and specificity on observational studies of influenza vaccine effectiveness.   Vaccine. 2015;33(11):1313-1316. doi:10.1016/j.vaccine.2015.01.069PubMedGoogle ScholarCrossref

Japan reports first case of mysterious children’s liver disease as health experts explore possible Covid links

Authors: Karen Gilchrist PUBLISHED TUE, APR 26 2022 CNBC

KEY POINTS

  • Japan has detected its first probable case of a mysterious liver disease that has so far affected over 170 children, largely in Britain.
  • Health experts are exploring its possible links to Covid-19 or a common virus known as adenovirus.
  • Of those infected, one child has died and 17 have required liver transplants.

Japan has detected its first probable case of a mysterious liver disease that has so far affected over 170 children, largely in Britain, as health experts explore its possible links to Covid-19.

Japan’s Health Ministry said Tuesday that a child had been hospitalized with an unidentified type of severe acute hepatitis — or liver inflammation — in what is thought to be the first reported case in Asia.

As of April 23, at least 169 cases of the disease have been detected in 11 countries globally, according to the World Health Organization. The vast majority of those have been in the U.K. (114), followed by Spain (13), Israel (12) and the U.S. (9). The addition of Japan marks the 12th country to identify a case.

Of those infected, one child has died and 17 have required liver transplants.

The WHO said it is “very likely more cases will be detected before the cause can be confirmed.”

Health experts explore Covid links

Children aged five years old or younger have so far been the most widely affected by the disease, though cases have been detected in children aged one month to 16 years.

Common symptoms including gastroenteritis — diarrhea and nausea — followed by jaundice or yellowing of the skin and eyes.

Health experts are now investigating the likely cause of the outbreak, which was first reported in the U.K. in January 2022, and whether it bears any connection to the coronavirus.

Specifically, they are exploring if a lack of prior exposure to common viruses known as adenoviruses during coronavirus restrictions, or a previous infection with Covid-19, may be related. Alternatively, the genetic make-up of hepatitis may have mutated, resulting in an easier triggering of liver inflammation.

Crucially, experts say there is no known link to the Covid-19 vaccine.

A strain of adenovirus called F41 is so far looking like the most probable cause, according to the U.K. Health Security Agency.

“Information gathered through our investigations increasingly suggests that this rise in sudden onset hepatitis in children is linked to adenovirus infection. However, we are thoroughly investigating other potential causes,” Meera Chand, UKHSA’s director of clinical and emerging infections, said.

Adenovirus was the most common pathogen detected in 40 of 53 (75%) of confirmed cases tested in the U.K. Globally, that number was 74.

Covid (SARS-CoV-2) was identified in 20 cases of those tested globally. Adenovirus and Covid-19 co-infection was detected in 19 cases.

The new case from Japan tested negative for adenovirus and the coronavirus, though officials have not revealed other details.

What are the symptoms and how worried should we be?

Typically, children gain exposure — and immunity — to adenoviruses and other common illnesses during their early childhood years. However, pandemic restrictions largely limited that early exposure, leading to more serious immune responses in some.

Adenoviruses, which present cold-like symptoms such as fever and sore throat, are generally mild. However, some strains can display liver tropism, or a favoring of liver tissue, which can lead to more serious consequences like liver damage.

Just how serious this latest outbreak will be is not yet clear and will depend largely on how much it spreads over the coming months, according Dr. Amy Edwards, an assistant professor of pediatrics at the Case Western Reserve School of Medicine.

“Adenovirus is a ubiquitous virus and it’s not seasonal. If this is a more severe form of adenovirus that causes liver disease in children, that’s very concerning. But right now it’s isolated enough and few enough cases not to jump to conclusions,” she told CNBC.

Edwards said health authorities had been placed on alert and would be monitoring the situation.

In the meantime, parents and guardians should be alert to common signs of hepatitis, including jaundice, dark urine, itchy skin and stomach pain, and contact a health care professional if they are concerned.

“Normal hygiene measures such as thorough handwashing (including supervising children) and good thorough respiratory hygiene, help to reduce the spread of many common infections, including adenovirus,” UKHSA’s Chand said.

“Children experiencing symptoms of a gastrointestinal infection including vomiting and diarrhea should stay at home and not return to school or nursery until 48 hours after the symptoms have stopped,” she added.

Children get long Covid, too, and it can show up in unexpected ways

Authors: Jen Christensen, Fri May 6, 2022 CNN

November 10 is a day Kim Ford remembers too well. It was the day last year when her 9-year-old son, Jack, was scheduled to get his Covid-19 vaccine at the school clinic. They were excited that he’d finally have some protection, but on November 9, he had the sniffles. “When he woke up [November 10] and he was feeling even worse, I said, ‘You know what, let’s test you before you go in, because I don’t want you to get the Covid vaccine if you actually have Covid,’ ” the Michigan mom said.

Jack tested positive for Covid-19 that day and he’s lived with the symptoms ever since. it has kept him from staying at school all day. He has to limit how much he plays baseball with the other neighborhood kids. Even playing Fortnite for too long can leave him feeling sick the next day.

He’s one of potentially millions of kids with long Covid.

“My stomach hurts. It’s kind of hard to breathe. You have a stuffy nose. It’s just an absurd amount of things that you can feel,” Jack Ford said. “It’s really annoying at times. It’s not like a cold, you know, it feels like Covid.”People may think you’re feeling faking it, but you’re not faking it. You feel like you have Covid,” he added.

‘An undiagnosed issue’

It’s not clear how many children go on to develop long Covid, because there’s not enough research on it in this age group, some experts say.

Almost 13 million children have tested positive for Covid-19 since the start of the pandemic, according to the American Academy of PediatricsStudies suggest that between 2% and 10% of those children will develop long Covid, but the number may be larger. Many parents may not know their child has long Covid, or the child’s pediatrician hasn’t recognized it as such. In adults, some research puts the number around 30% of cases .”I personally believe that this is a very much an undiagnosed issue,” said Dr. Sara Kristen Sexson Tejtel, who helps lead a long Covid pediatric clinic at Texas Children’s Hospital in Houston. Many doctors treating children at long Covid clinics across the country say they have long waits for appointments. Some are booked through September.

An unusual range of symptoms

There are no specific tests for long Covid. It’s not clear which children will have it, as it can happen even when a child has a mild case of Covid-19.

“It’s startling how many of these children present and have a range of symptoms that we haven’t fully appreciated. Some are coming in with heart failure after asymptomatic Covid infections,” said Dr. Jeffrey Kahn, chief of the Division of Pediatric Infectious Disease at UT Southwestern Medical Center in Dallas. “What’s striking to me is that it usually occurs about four weeks after infection, and infection can be really asymptomatic, which is really startling. “Even when kids with long Covid are tested for ailments that might cause these symptoms, it’s possible nothing will show up.”The tested me, and it looked like nothing was wrong with me, but they tried their best to find something,” Jack Ford said. His pulmonary function test and EKG came back normal. “The Covid clinic said this is very common in kids with long Covid. Sometimes, all the tests come back normal,” Kim Ford said.

Dr. Amy Edwards, who runs the pediatric long Covid clinic at UH Rainbow Babies & Children’s Hospital in Cleveland, agreed that it happens a lot. “We also scoped them, and their GI tracts are normal. I do a big immune workup, and their immune system appears normal. Everything ‘looks normal,’ but the kids aren’t functioning like normal,” Edwards said. “I tell the families, ‘you have to remember, there are limits to what medical science understands and can test for.’ Sometimes, we’re just not smart enough to know where to look for it. Adults’ problems tend to be more obvious, Edwards said, because they are more likely to have organ dysfunction that shows up on tests. Doctors are still trying to understand why long Covid happens this way in children. They are also figuring out what symptoms define long Covid in children. Some studies in adults show a range of 200 symptoms, but there is no universal clinical case definition.

Public health leaders hope stories about long Covid will motivate more young people to get vaccinatedAt Sexson Tejte’s clinic in Texas, children tend to fall into a few categories. Some have fatigue, brain fog and severe headaches, “to the point where the some kids aren’t able to go to school, grades are failing, those types of issues,” she said.Another group has cardiac issues like heart palpitations, chest pains and dizziness, especially when they go back to their regular activities.Another group has stomach problems. A lot of these kids also have a change in their sense of taste and smell.Sexson Tejte said it isn’t totally different from the symptoms adults have, “but it’s not the mixed bag of different organ system involvement with adults.”

‘Once that bucket is empty, that’s it’

One of Jack Ford’s symptoms affects the amount of energy he has for typical activities.

“Long Covid patients have post-exertional malaise, which is Jack’s biggest issue,” Kim Ford said. “So if he overdoes it — and it doesn’t even have to be physically overdoing it. It could be he was really upset about something the day before, or he could be really mentally engaged with something like watching TV or playing video games sitting in his chair — will knock him out. “Energy has become such a problem that Jack can’t go to school for a full day. His parents started him back with one to two hours a day and have gradually increased it to about 5½ hours a day. “We’ve been trying to bump him up to six, but it hasn’t worked so far,” Kim Ford said. “He’s woken up pretty miserable the next day. “Edwards, who runs the long Covid clinic in Cleveland, says she has to talk to parents about carefully balancing how much energy their children expend. Most healthy people can push through if they’re tired, but those with long Covid can’t. “It’s like they have one bucket of energy, and it has to be used carefully for school, for play, to watch TV. Every single thing they do takes energy, and once that bucket is empty, that’s it,” Edwards said.

‘I barely function some days’: Covid ‘long haulers’ struggle to work amid labor of her teen patients are exhausted just dealing with typical drama at school. “Long-haulers have to think about every single aspect of their day and when they can expend that energy. They have to have that balance. Otherwise, they run out. “Many also have anxiety. Some of that may stem from the ailment itself or from the doubt they’ve heard from doctors or adults when they say they don’t feel well. Experts across the country say they’ve heard from patients whose complaints are ignored, even after a stark change in their health. They’ve been told that they are being dramatic or seeking attention, or that the symptoms are all in their head.

I don’t want to be too critical, but there are some doctors out there who just dismiss it outright,” said Dr. Alexandra Yonts, director of the post-Covid clinic at Children’s National in Washington. “The kids then just struggle. They get passed around from place to place.”Yonts thinks there needs to be better acknowledgment among doctors that long Covid can be a real problem .”I’ve got two kids in wheelchairs after having had Covid who were never in wheelchairs before. There’s one kid on crutches. I’ve got a kid who lost the use of her hands,” Edward said. “These kids should be believed.”

Help is available, but not all have access

There’s no specific treatment for long Covid, but most of these clinics are multi-disciplinary. Interactive: The things Covid victims left behind At Edwards’ clinic, which opened last year, experts can address pulmonary issues, digestive problems, physical rehabilitation, sleep issues, mental health problems and others. There’s a nutritionist on staff, as well as an acupuncturist and a pediatrician who is licensed in Chinese herbal medicine. In addition to working up a child’s schedule so they can determine where to spend their energy and when to take breaks, Edwards’ clinic teaches kids to meditate. They do massage therapy and mind-body exercises. “Children need multiple elements of help. They get significantly better, really they do, if we’re aggressive and they get intensive wraparound support and therapy,” Edwards said. But not all children are able to get into a clinic. “I’ve talked to so many people working with pediatric Covid recovery, and they all say the same thing: ‘We are worried about the kids who aren’t getting the help, who don’t have the parents who can advocate for them or navigate the medical system.’ It keeps me up at night,” Edwards said.

A lot of what her clinic does is to encourage kids to get enough sleep and to eat healthy food, but not all families can afford healthy food.”It terrifies me for those families in particular, because they’re already starting behind. And now they have kids with Covid long-haul,” Edwards said. “You just have to hope more people will become aware of the problem and try to help.”

SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis

Authors: RALPH TURCHIANO    • 

Abstract

Establishing the rate of post-vaccination cardiac myocarditis in the 12-15 and 16-17-year-old population in the context of their COVID-19 hospitalization risk is critical for developing a vaccination recommendation framework that balances harms with benefits for this patient demographic. Design, Setting and Participants: Using the Vaccine Adverse Event Reporting System (VAERS), this retrospective epidemiological assessment reviewed reports filed between January 1, 2021, and June 18, 2021, among adolescents ages 12-17 who received mRNA vaccination against COVID-19. Symptom search criteria included the words myocarditis, pericarditis, and myopericarditis to identify children with evidence of cardiac injury. The word troponin was a required element in the laboratory findings. Inclusion criteria were aligned with the CDC working case definition for probable myocarditis. Stratified cardiac adverse event (CAE) rates were reported for age, sex and vaccination dose number. A harm-benefit analysis was conducted using existing literature on COVID-19-related hospitalization risks in this demographic. Main outcome measures: 1) Stratified rates of mRNA vaccine-related myocarditis in adolescents age 12-15 and 16-17; and 2) harm-benefit analysis of vaccine-related CAEs in relation to COVID-19 hospitalization risk. Results: A total of 257 CAEs were identified. Rates per million following dose 2 among males were 162.2 (ages 12-15) and 94.0 (ages 16-17); among females, rates were 13.0 and 13.4 per million, respectively. For boys 12-15 without medical comorbidities receiving their second mRNA vaccination dose, the rate of CAE is 3.7-6.1 times higher than their 120-day COVID-19 hospitalization risk as of August 21, 2021 (7-day hospitalizations 1.5/100k population) and 2.6-4.3-fold higher at times of high weekly hospitalization risk (2.1/100k), such as during January 2021. For boys 16-17 without medical comorbidities, the rate of CAE is currently 2.1-3.5 times higher than their 120-day COVID-19 hospitalization risk, and 1.5-2.5 times higher at times of high weekly COVID-19 hospitalization. Conclusions: Post-vaccination CAE rate was highest in young boys aged 12-15 following dose two. For boys 12-17 without medical comorbidities, the likelihood of post vaccination dose two CAE is 162.2 and 94.0/million respectively. This incidence exceeds their expected 120-day COVID-19 hospitalization rate at both moderate (August 21, 2021 rates) and high COVID-19 hospitalization incidence. Further research into the severity and long-term sequelae of post-vaccination CAE is warranted. Quantification of the benefits of the second vaccination dose and vaccination in addition to natural immunity in this demographic may be indicated to minimize harm.

Millennials Experienced the “Worst-Ever Excess Mortality in History” – An 84% Increase In Deaths After Vaccine Mandates

The most recent data from the CDC shows that U.S. millennials, aged 25-44, experienced a record-setting 84% increase in excess mortality during the final four months of 2021, according to the analysis of financial expert and Blackrock whistleblower, Edward Dowd,

Dowd, with the assistance of an insurance industry expert, compiled data from the CDC showing that, in just the second half of 2021, the total number of excess deaths for millennials was higher than the number of Americans who died in the entirety of the Vietnam War. Between August and December, there were over 61,000 deaths in this age group, compared to 58,000 over the course of 10 years in Vietnam.

In all, excess death among those who are traditionally the healthiest Americans is up by 84%.

Long COVID in Children

Observations From a Designated Pediatric Clinic

Authors: Ashkenazi-Hoffnung, Liat MD*,†; Shmueli, Einat MD*,†; Ehrlich, Shay MD*,†; Ziv, Adi MD*,†; Bar-On, Ophir MD*,†; Birk, Einat MD*,†; Lowenthal, Alexander MD*,†; Prais, Dario MD*,†

Abstract

Systematic data are lacking on pediatric long COVID. This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID. In nearly 60%, symptoms were associated with functional impairment at 1–7 months after the onset of infection. A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients, mainly in the respiratory aspect.

Long-term follow-up of adults diagnosed with acute coronavirus disease 2019 (COVID-19) has shown that a substantial proportion experience persisting symptoms months after the initial diagnosis.1,2 To date, systematic data are lacking on long COVID or postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children.3 We prospectively analyzed persistent symptoms in children who recovered from COVID-19, and described the diagnostic yield of a comprehensive clinical evaluation.

METHODS

This study prospectively assessed children ≤18 years of age who presented to a designated multidisciplinary clinic for long COVID, at a tertiary pediatric center, from November 2020 to April 2021, following referral by their general practitioner. SARS-CoV-2 infection was microbiologically confirmed by real-time quantitative reverse transcription polymerase chain reaction during acute infection or by subsequent serology using an in-house enzyme-linked immunosorbent assay (The Central Virology Laboratory of the Ministry of Health at Sheba Medical Center, Tel Hashomer) until mid-March and Abbot ARCHITECT SARS-CoV-2 IgG Immunoassay, thereafter. All the patients underwent a structured evaluation >4 weeks from diagnosis. This included assessment of symptoms and their impact on daily activities by means of a structured interview conducted by a senior pediatrician with >10 years’ experience; a physical examination, blood tests, electrocardiograph and a chest radiograph. In the event of cardiorespiratory symptoms, a pulmonary function test (for children older than 6 years) and echocardiography were performed. Further testing, such as bronchodilator response testing and cardiac magnetic resonance imaging (MRI), was done following abnormal findings on the initial evaluation. Additionally, data on background illnesses and on acute COVID-19 disease were retrieved from patients’ electronic files. Severity of the acute COVID-19 disease was classified according to the National Institute of Health symptom severity criteria.4

Persistent symptoms were stratified by age (≤11 versus >11 years) and compared by χ2 (IBM SPSS Statistics, Version 22.0). Written informed consent was obtained from parent or legal guardian; the study was approved by the institutional review board (RMC-20-0885).

RESULTS

Ninety children, mean age 12 ± 5 years, were assessed at a median of 112 days (range: 33–410) after COVID-19 diagnosis. One adolescent who tested positive for COVID-19 was excluded from the analysis because during the initial evaluation, diabetic ketoacidosis was diagnosed; following medical care, his symptoms of fatigue and weight loss resolved. The cohort comprised mainly previously healthy children who exhibited a mild symptomatic acute disease (Table 1). The sex ratio showed a minor male predominance. Twenty-five percent were overweight, with a body mass index >85th percentile for age, in accordance with national published rates.5 The most common reason for patient referral was dyspnea (30, 33.3%), followed by myalgia (12, 13.3%) and headache (8, 8.8%).TABLE 1. – Demographic and Clinical Characteristics of 90 Children with Long COVID, and the Main Features of the Medical Evaluation

General CharacteristicsN (%)
Age, mean ± SD, yrs12 ± 5
Gender, male:female1.4:1
BMI percentile by WHO growth charts > 8523 (25.6)
Very early preterm birth <32 wks gestation2 (2.2)
Early preterm birth 32–36 wks gestation3 (3.3)
Background medical conditions
 Immunodeficiency*5 (5.6)
 Autoimmune or inflammatory disease4 (4.5)
 Asthma2 (2.2)
 Anxiety or depressive disorder3 (3.3)
 Attention deficit hyperactivity disorder12 (13.3)
 Other33.3
Participation in competitive sports12 (13.3)
Severity of the acute COVID-19 illness§: asymptomatic3 (3.3)
 Mild82 (91.1)
 Moderate6 (6.7)
 Severe2 (2.2)
Hospitalization during the acute illness11 (12.2)
Positive COVID-19 qRT-PCR during the acute illness, n = 8989 (100)
COVID-19 serology during evaluation, n = 72, positive58 (80.6)
 Borderline5 (5.6)
PIMS before evaluation1 (1.1)
Medical evaluation
 Positive findings on physical examination5 (5.6)
 Laboratory investigation**
 Sedimentation rate > 20 mm/h or C-reactive protein > 0.5 mg/dL4 (4.9)
  Troponin≥ 14 ng/L1 (1.3)
  Creatine phosphokinase ≥ 200 units/L11 (14.1)
  Ferritin ≤ 20 µg/L29 (43.9)
  Hemoglobin ≤ 11 g/dL3 (3.6)
 Pulmonary evaluation
  Chest radiograph changes12 (133)††
  Pulmonary function tests
   Abnormal spirometry, FEV1 < 80% or FEV1/FVC < 0.8, n = 605 (8.3)
  Abnormal exercise challenge test,‡‡ ΔFEV1 ≥ 12%, n = 513 (5.9)
  Positive bronchodilator response, ΔFEV1 ≥ 12%, n = 2915 (51.7)
  Air trapping by plethysmography, RV/TLC > 125%, n = 5515 (27.3)
  Diffusion capacity < 70%, n = 501 (2.0)§§
 Cardiac evaluation
  Abnormal findings on electrocardiograph2 (2.2)¶¶
  Abnormal findings on echocardiography, n = 630 (0)
  Abnormal holter, n = 40 (0)
  Abnormal cardiac MRI, n = 31 (33.3)
 Maximal pulse during exercise stress test <180 b/min,6 n = 5134 (66.7)

BMI, body mass index; FEV1, forced expiratory volume in the first second; FEV1/FVC, ratio of FEV1 to forced vital capacity; PIMS, pediatric inflammatory multisystem syndrome; qRT-PCR, quantitative reverse transcription polymerase chain reaction; RV/TLC, ratio of residual volume to total lung capacity; WHO, World Health Organization.*Including, kidney transplantation due to microscopic polyangiitis (1), kidney transplantation due to Schimke immuno-osseous dysplasia (1), glioma with chemotherapy (1), s/p bone marrow transplantation due to myelodysplastic syndrome (1), asplenia due to spherocytosis (1).†Including, Crohn’s disease (1), Familial Mediterranean Fever (1), type 1 diabetes (1), celiac disease (1).‡Including, dysplastic kidney (1), bilateral cochlear implant (1), convulsive disorder (1).§By the National Institute of Health symptom severity criteria.4¶In 4 adolescents, serology was taken after 1 dose of BNT162b2 (Pfizer-BioNTech COVID-19 vaccine).‖Including, decreased muscle strength, dyspnea or tremor.**Serum was depleted in 17 children; One patient refused blood tests.††Including infiltrates (7), peribronchial thickening (3) and interstitial pattern (1).‡‡The exercise test was terminated prematurely in four patients due to dyspnea or myalgia.§§S/p severe acute COVID-19.¶¶Inverted T waves and ST segment elevation.

The median number of reported symptoms was 4 (range: 1–14). Fatigue (64, 71.1%), dyspnea (45, 50.0%) and myalgia (41, 45.6%) were the most frequently reported symptoms, and were significantly associated with older age >11 years (Table 1, Supplemental Digital Content 1, https://links.lww.com/INF/E492). Additional persistent symptoms included sleep disturbances (30, 33.3%), chest pain (28, 31.1%), paresthesia (26, 28.9%), headache (26, 28.9%), hair loss (24, 26.7%), anosmia-ageusia or parosmia/euosmia (23,25.6%), gastrointestinal symptoms (18, 20.0%), dizziness (17, 18.9%), weight loss of >5% of body weight (17, 18.9%), memory impairment (16, 17.8%), vasomotor complaints (13, 14.4%), arthralgia (13, 14.4%), tremor (12, 13.3%), cough (9, 10.0%), palpitations (8, 8.9%), difficulty in concentration (8, 8.9%), tic exacerbation (2, 2.2%) and tinnitus (1, 1.1%). Uncommon symptoms in young children included recurrent febrile episodes (2, 2.2%), developmental regression (2, 2.2%) and obstructive sleep apnea (2, 2.2%). These were temporally associated with COVID-19 infection, had no alternative explanation despite a comprehensive evaluation and resolved after about 10–12 weeks. Fifty-three children (58.9%) reported impairment in daily activities due to symptoms.

The comprehensive medical evaluation revealed abnormal findings in a substantial number of patients, mainly in the respiratory aspect. Twenty-seven (45.0%) of 60 patients who underwent pulmonary function tests due to cardiorespiratory symptoms had abnormal findings. These were compatible with a mild obstructive pattern, as evident by low values of forced expiratory volume in the first second on spirometry, and by air trapping on lung volume evaluation. Following bronchodilators in the patients with abnormal or borderline pulmonary function tests, more than half (15/29) exhibited reversibility of the obstructive defect (Table 1). Abnormal pulmonary function tests were not associated with a history of atopy (8/27 vs. 13/33, P = 0.431).

For all 51 patients who underwent an exercise stress test, the maximal pulse was lower than the age-specific mean; for 34 (66.7%), the value was below the minimal threshold value (−2 SDs),6 suggesting some degree of chronotropic incompetence. Cardiac investigation was mostly normal; echocardiography showed normal left ventricular ejection fraction and the absence of pulmonary hypertension in all 63 patients. Abnormal findings on electrocardiograph were found in 2 adolescent patients who previously participated in competitive sports. One of them had transiently elevated troponin levels and mild lateral wall thickening on cardiac MRI. Significant laboratory findings were elevated levels of creatine phosphokinase and low ferritin levels (Table 1).

DISCUSSION

This prospective cohort preliminary study provides a detailed description of the continuum of persisting symptoms in children with long COVID and the results of their medical investigation at a designated pediatric clinic. Despite a mild acute disease and lack of background illness in the vast majority, for nearly 60%, symptoms were associated with functional impairment at 1–7 months after the onset of infection. The 2 most common symptoms were fatigue and dyspnea, as has been described in adults.1,2 However, obstructive sleep apnea and developmental regression were not previously described and warrant further research. Interestingly, several symptoms were more common among older children. In contrast to reports in adults in which females were at greater risk for long COVID,7 our cohort showed a minor male predominance. Also, among adults, it was suggested that obesity is associated with a greater risk of long COVID;8 this suggestion was not supported by the normal weight distribution of our cohort population.

Although radiologic and spirometric changes were mild, they were observed in more than half the patients. This supports the importance of pulmonary evaluation, and the potential for treatment with bronchodilators and inhaled corticosteroids. Another treatment approach may focus on dietary habits and may include ferritin in the laboratory workup. Conversely, none of the children exhibited abnormal findings on echocardiography, raising questions as to its necessity in children, in the presence of a normal electrocardiograph.

The study is limited by the small sample size and single-center design; however, it lays the groundwork for designing therapeutic interventions for long COVID in children. Also, a baseline pre-COVID evaluation of the patients is lacking. In addition, since the study was not population-based, the prevalence of long COVID could not be assessed. However, this was not the aim of the study, but rather to describe the range of symptoms and the diagnostic yield of the medical investigation.

In conclusion, this study confirms the morbidity associated with long COVID in children, and highlights the need for multidisciplinary pediatric clinics for evaluation and treatment.

REFERENCES

1. Carfì A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent symptoms in patients after acute COVID-19. JAMA. 2020;324:603–605.View Full Text |  PubMed |  CrossRef

2. Tenforde MW, Kim SS, Lindsell CJ, et al.; IVY Network Investigators; CDC COVID-19 Response Team; IVY Network Investigators. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a Multistate Health Care Systems Network – United States, March-June 2020. MMWR Morb Mortal Wkly Rep. 2020;69:993–998. PubMed |  CrossRef

Spotting Long COVID Symptoms in Children

Authors: Katie Sweeney Published on November 17, 2021 Categories: COVID-19Hospital Programs

It’s one of the more mysterious aspects of COVID-19—a condition called long COVID. While most people recover from the virus within two to four weeks, others can struggle for months afterward with lingering, often debilitating symptoms.

Long COVID has been most commonly talked about in adults, but children can experience it, too—even if they didn’t have any symptoms with their initial COVID infection. That can make the condition challenging to diagnose.

“Many children don’t have any symptoms when they have a COVID infection,” says Sindhu Mohandas, MD, a pediatric infectious disease specialist and Attending Physician at Children’s Hospital Los Angeles. “So if the symptoms of long COVID appear later, it can be difficult to link them to the coronavirus.”

Is it long COVID?

Unlike COVID-19, there is no simple nasal swab or other diagnostic test for long COVID. Doctors instead look at a child’s pattern of symptoms, as well as past exposure to the virus.

Those symptoms can vary widely from patient to patient, but in children, the most common long COVID symptoms are:

  • Unusual tiredness/fatigue
  • Headaches
  • Difficulty concentrating, or “brain fog”

Children can also experience:

  • Shortness of breath
  • Sore throat
  • Unexplained fevers
  • Exercise intolerance
  • Fast heartbeat
  • Chest pain
  • Loss of smell or taste
  • Muscle or nerve pain
  • Sleep disorders
  • Diarrhea, vomiting or constipation
  • Anxiety
  • Depression

Long COVID symptoms are persistent, lasting more than four weeks after a COVID-19 infection. Symptoms can vary between children. For example, one child may have a headache for a couple of hours every day, where another may have a headache a few times a week.

The condition also interferes with normal activities. A child who was previously a strong student may now have difficulty completing assignments. An athlete may no longer have the energy to take part in sports.

“Long COVID can be more severe in some patients than in others,” Dr. Mohandas notes. “But it can significantly impact the quality of life for the child, and consequently the entire family.”

Past exposure to COVID

Symptoms alone are not enough to diagnose long COVID, though, especially since they can be caused by other conditions. That’s why doctors also look for whether a child was previously exposed to the coronavirus.

This link is much easier to make for children who had a positive COVID-19 test or clear COVID symptoms in the past. For those who were never tested or never felt sick, doctors look closely at the family history and whether there were any known virus exposures for the child.

Antibody tests can indicate a past COVID infection, too. “The one caveat is that if a child is vaccinated, the antibodies may be because of the vaccine and not infection,” Dr. Mohandas explains. “However, we can order a test that distinguishes between those different antibodies.”

Long COVID treatment

Although there is no definitive cure for long COVID, But it is still important for children to be diagnosed, because often the symptoms can be managed.

“If you think your child might have long COVID, or you’re just worried about the symptoms, see your pediatrician,” she says. “Even if it’s not long COVID, there could be something else going on. Your doctor will be able to evaluate your child and decide if the child needs to be seen at a specialized center.”

This past summer, Children’s Hospital Los Angeles launched a dedicated Long COVID Recovery Care service—one of only a few of its kind for children in California. Dr. Mohandas says many families she’s seen struggled for months to find a diagnosis before coming to Children’s Hospital.

“These families are so grateful to finally understand what is happening with their child,” she adds.

A thorough exam can help rule out other causes for a child’s symptoms or help pinpoint if specific organs are affected. For example, if a child is having chest pain, an EKG and echocardiogram (ultrasound of the heart) can check for structural changes or damage to the heart.

Fortunately, children with long COVID typically do get better, though it can sometimes take many months.

“The most important thing is time and rest,” Dr. Mohandas says. “But we may also be able to provide supportive care to help manage a child’s symptoms. All this can be done safely if we’ve ruled out other conditions or causes.”

‘The million-dollar question’

So far, it seems that long COVID is more common in adolescents 12 and older than in younger children. But that’s not known for sure. In fact, little is understood about how many children get long COVID—or why they get it in the first place.

“That’s the million-dollar question right now,” Dr. Mohandas says. “The most important thing is defining how prevalent this problem is in children, and then we need to understand why it’s occurring. If we can understand the cause, we can then develop treatments.”

Children’s Hospital Los Angeles is actively trying to find those answers. Recently, the hospital was awarded $8.3 million from the National Institutes of Health to participate in a national study called RECOVER (Researching COVID to Enhance Recovery). The study aims to better understand the after-effects of COVID-19 infection.

In the meantime, Dr. Mohandas stresses that the best strategy for long COVID is prevention.

“It is critically important to get children vaccinated when they are eligible, and to follow local masking and distancing guidelines,” she says. “The best thing you can do to prevent long COVID is to prevent COVID-19.”

What Happens When Kids Get Long COVID?

Authors: KATHY KATELLA  NOVEMBER 2, 2021

Yale’s pediatric post-COVID program provides care, while doctors aim to learn more.

Doctors are working to understand why some children and adolescents who get COVID-19 make a clean recovery, while others go on to develop long COVID, a condition marked by new, returning, or ongoing symptoms such as brain fog and chronic fatigue. The question of why some kids (just like some adults) wrestle with health problems for weeks or months is one of the pandemic’s biggest mysteries—and one that causes worry for parents.

With long COVID, many kids suddenly find themselves struggling to keep up with their schoolwork or skipping sports. Others can’t sleep or have difficulty walking, while yet others struggle with aches and pains, breathlessness, dizziness, and other troubling symptoms.

Yale Medicine doctors are treating children with long COVID, as well as studying the causes and potential solutions for it, in the Children’s Post-COVID Comprehensive Care Program, offered in the Pediatric Specialty Clinic in Yale New Haven Children’s Hospital. The program, which opened in June of this year, is one of a handful in the country specializing in treating pediatric long COVID patients. They’ve seen patients from infancy through the teenage years.

Severity of symptoms has ranged widely. Some of these patients didn’t even know they had COVID until their long COVID symptoms developed. Others had been diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), a rare, but serious condition that affects multiple organs. Then, there are children who struggle with a long list of post-COVID-19 symptoms that include lingering physical, neurological, and mental problems.

Treatment for pediatric long COVID is a work in progress, but doctors have already learned a great deal about how to help these patients. Here are some common questions parents are asking about the condition and some answers, based on the most current knowledge.  

How common is long COVID in kids?

As of the end of October, nearly 6.4 million children had been diagnosed with COVID-19, according to the American Academy of Pediatrics (AAP)—but studies quantifying the number of cases of long COVID in kids have varied widely. Geography is one factor. “Different studies have shown different results, depending on what parts of the world or which parts of the country you’re looking at,” says Carlos Oliveira, MD, a pediatric infectious diseases specialist.

Another issue is the lack of a clear definition—or even a consistent name—for the disease. It has been called long-haul COVID, post-acute COVID-19, and post-acute sequelae of SARS-CoV-2 infection (PASC), the latter being a research term (“sequelae” means, simply, a medical condition that results from a prior disease). “If you include every child who has been hospitalized with MIS-C, [by definition a complication of acute COVID], you’ll come up with a higher prevalence,” Dr. Oliveira says. As of October 4, there had been more than 5,210 cases of MIS-C and 46 deaths, according to the Centers for Disease Control and Prevention (CDC).

Only a fraction of children with long COVID seek medical attention, which makes tracking its incidence very challenging, he adds. Also, because infants and toddlers can’t always verbalize what they are feeling, it makes matters more complicated. Symptoms like fatigue, for instance, can manifest in young children as hyperactivity rather than sluggishness, making it difficult for parents to detect the problem. “As a result, we are likely only identifying the adolescents who can self-report their symptoms,” he says. 

Are post-COVID symptoms different in kids than in adults?

Dr. Oliveira says that kids often display different symptoms than adults, with no single standout symptom that makes a case easy to identify. The AAP reports that children and adolescents have experienced chest pain, cough, exercise-induced dyspnea (or labored breathing), as well as changes to smell or taste (although this is more common in adolescents), among other things. Affected children and teens have reported fatigue, brain fog, anxiety, joint pain, headache, and sore throat, among other symptoms—all varying in intensity and duration, in some cases lasting for months. 

Ian Ferguson, MD, a Yale Medicine rheumatologist has been caring for pediatric patients with long COVID who have joint and bone pain. “What I tend to see is a generalized achiness and a decrease in physical conditioning,” Dr. Ferguson says. “They might say, ‘I just feel achy. I don’t feel right.’ An otherwise healthy child may say, ‘I don’t feel like I should get out of bed in the morning.’ Or they say, ‘I used to be on the high school cross country team. And now I can barely make it down the street before I have to take a break.’”

“Sometimes the expectation from a parent is that their pediatrician will know everything about this… But, this is a new disease, and doctors are still learning.”— Carlos Oliveira, MD, a pediatric infectious diseases specialist

Some children experience subtle symptoms but, when diagnostic testing is done, no abnormalities are found, Dr. Oliveira says. For example, a child may have pain, fatigue, or trouble concentrating, but their imaging and bloodwork come back normal. “Often, we call these symptoms ‘medically unexplained,’ but they are still obviously very significant to the patient’s health,” he says. “The child may not be able to go to school or may not be able to walk, and we can’t find a reason why.”

A very small percentage of children even develop serious complications, since COVID-19 can affect organs including the brain, heart, kidneys, and liver—and any of those organs can be damaged if the child doesn’t receive proper care. “The post-COVID clinic is meant to identify these symptoms caused by residual organ damage and treat them,” Dr. Oliveira says.

Is inflammation a cause of post-COVID symptoms in children?

Experts are still trying to figure out what causes long COVID in kids. “The main hypothesis—I say hypothesis because we don’t yet know—is that there’s some continual trigger of inflammation,” Dr. Oliveira says.

He explains that some of the different ways that COVID manifests in children may contribute to a greater likelihood of ongoing inflammation. For instance, when a child gets COVID, the virus is more apt to concentrate in the gut than in the lungs, making symptoms more likely to be gastrointestinal than respiratory. It may also take longer to clear the virus from a child’s system than it does for an adult, he adds. “We don’t fully understand why, but we know that with kids, if we were to test their stool three or four months post-infection, for many of them, we would still find noninfectious remnants of the virus. It may be nonviable virus, but the remnants are still there.”  

“You can look at the lab tests… and they’re not showing anything. But that doesn’t mean that the immune system didn’t ramp up… and cause those symptoms.”— Ian Ferguson, MD, a Yale Medicine rheumatologist

And those pieces of remnant virus can continually trigger inflammation. “The immune system will attack those pieces of remnant virus and cause inflammation, because it can’t distinguish between a live virus and the remnants of one. The immune system just sees viral antigens [the molecular structures on the surface of the virus] and wants to get rid of them,” Dr. Oliveira says.

The hypothesis is that there may be continual exposure of viral antigens to the immune system in some children with long COVID, triggering persistent or intermittent inflammation, albeit at a milder level since the remnant virus is not able to make copies of itself, he says. “This kind of inflammation is more like a ‘slow burn’ for a long period of time, rather than the acute inflammation of MIS-C,” he adds. Treatment with anti-inflammatories may be helpful in this situation, he says, but studies are still ongoing.

There is support for the “slow burn” theory in that some long COVID symptoms tend to improve after patients receive a COVID-19 vaccine, which triggers a boost in antibodies that presumably clears the viral antigens more effectively.

What is the treatment for kids with long COVID?

There is no typical case of long COVID in kids, and no one-size-fits-all treatment. Young patients who visit the Yale program come in with any combination of symptoms.

Typically, after a full evaluation, patients are referred to one or more subspecialists with expertise in a particular area. Long COVID can affect different organs and parts of the body, so in addition to pediatric infectious diseases specialists, the team can include cardiologists, neurologists, pulmonologists, rheumatologists, psychologists, and others.

Treatment tends to be most effective when it addresses each symptom individually. A child with chest pain and decreasing physical conditioning will be referred for a cardiac evaluation, for instance, while one with cognitive challenges will be seen by a neurologist. 

Treatment strategies can also draw from those used for other illnesses that bring lingering symptoms, such as the prolonged fatigue after mononucleosis (or ‘mono’). “In rheumatology, we see a lot of unexplained achiness, which provides us with a fairly reasonable framework,” says Dr. Ferguson. “You can look at the lab tests or at the imaging studies, and they’re really not showing anything. That doesn’t necessarily mean that the immune system didn’t ramp up at some point and cause those symptoms. Therefore, many of our recommendations are framed as, ‘Let’s figure out how to build this child’s health back up.’”

So, for example, once a cardiologist says a patient’s heart is fine and a breathing test shows their oxygen exchange is good, doctors may tell them to gradually increase their physical conditioning by adding aerobic and muscular exercise over time. “Physical therapy is a great resource because the physical therapists not only observe patients in the clinic, they give patients a home exercise program that will help them build back up over time,” Dr. Ferguson says. “We anticipate most people will be able to regain their conditioning—albeit on a timeline that we really can’t dictate.” 

What helps when children with long COVID have mental health symptoms?

It’s common for children with long COVID to face mental health challenges as well—although whether that’s a direct result of COVID-19 is still unclear. “There is a worldwide increase in children’s behavioral health needs, especially around anxiety and depression, and that’s not only in children who have had COVID,” says Linda Mayes, MD, chair of the Yale Child Study Center (CSC), which participates in treating patients in the post-COVID treatment program. “We just don’t really know yet how COVID impacts basic psychological development overall.”

But there are ways doctors can help, regardless of the cause, she adds. For children who have learning needs or challenges, or problems paying attention, CSC specialists might work with the child’s school to help adjust curriculum or educational approaches for that child. If there are behavioral health needs, they provide psychotherapy and medications, as needed, and work directly with parents and families. “None of this is COVID-specific,” Dr. Mayes says. “It’s what we do every day. Over time, what will be important to know is, are those issues greater among children who have had COVID-19?”

In addition, CSC counselors provide strategies to help children in the program manage unexplained medical symptoms, including chronic pain. Biofeedback, cognitive behavioral therapy, and mindfulness techniques can all help, Dr. Mayes says. “Regardless of the origin, if a problem is related to COVID or anxiety, we have well-tested, evidence-based approaches,” she says. 

How long do children with long COVID need treatment?

It’s impossible to predict a long-term recovery timeline for children with long COVID, since doctors have only had a year and a half of experience with it. But the good news is that, so far, the children treated in the program are doing well, Dr. Oliveira says. “By numbers, relative to the adults, kids usually recover faster, within a few months.”

That said, he notes that some patients may continue to need monitoring for cardiac issues, and cardiologists may restrict their activities until they are confident that a child’s heart function is back to normal.

The doctors encourage pediatricians and parents to contact Yale’s pediatric post-COVID program if they have any serious physical or mental concerns about a child that could be related to having had COVID-19.

Even if they aren’t sure the child has had the illness, there may be some unknown association that is worth investigating. “Sometimes the expectation from a parent is that their pediatrician will know everything about this, and be able to diagnose it and treat it, just as they would with an ear infection,” Dr. Oliveira says. “But this is a new disease, and doctors are still learning.”

Children with long covid

Authors: Helen Thomson

New Sci. 2021 Feb 27; 249(3323): 10–11.Published online 2021 Mar 3. doi: 10.1016/S0262-4079(21)00303-1PMCID: PMC7927578PMID: 33686318

Abstract

Almost half of children who contract covid-19 may have lasting symptoms, which should factor into decisions on reopening schools,

A SERIOUS picture is emerging about the long-term health effects of covid-19 in some children, with UK politicians calling the lack of acknowledgment of the problem a “national scandal”.

Children seem to be fairly well-protected from the most severe symptoms of covid-19. According to the European Centre for Disease Prevention and Control, the majority of children don’t develop symptoms when infected with the coronavirus, or their symptoms are very mild.

However, it is becoming increasingly apparent that a large number of children with symptomatic and asymptomatic covid-19 are experiencing long-term effects, many months after the initial infection.Go to:

Long-term symptoms

Symptoms of long covid were first thought to include fatigue, muscle and joint pain, headache, insomnia, respiratory problems and heart palpitations. Now, support groups and researchers say there may be up to 100 other symptoms, including gastrointestinal problems, nausea, dizziness, seizures, hallucinations and testicular pain.

Most long covid research is based on adults. There is less information about under-18s, in part because it takes longer to get ethical approval to study children, says Natalie Lambert at Indiana University School of Medicine.

A recent study found that 13.3 per cent of adults with symptomatic covid-19 have symptoms lasting more than 28 days (medRxiv, doi.org/ghgdsv). Long-lasting symptoms were more likely to occur with increasing age and BMI, and were more likely in women than men, although it isn’t clear why. Experiencing more than five symptoms in the first week post-infection was associated with a greater likelihood of having symptoms further down the line.

Evidence from the first study of long covid in children suggests that more than half of children aged between 6 and 16 years old who contract the virus have at least one symptom lasting more than 120 days, with 42.6 per cent impaired by these symptoms during daily activities. These interim results are based on periodic assessments of 129 children in Italy who were diagnosed with covid-19 between March and November 2020 at the Gemelli University Hospital in Rome (medRxiv, doi.org/fv9t).

The UK Office for National Statistics’s latest report estimates that 12.9 per cent of UK children aged 2 to 11, and 14.5 per cent of children aged 12 to 16, still have symptoms five weeks after their first infection. Almost 500,000 UK children have tested positive for covid-19 since March 2020.

Most medical bodies say it normally takes a few days or weeks to recover from covid-19, and that most will make a full recovery within 12 weeks.

UK advocacy group Long Covid Kids says that it currently has details of 1200 children with long covid from 890 families in England. “And that number has been rising quickly,” says founder Sammie Mcfarland. “Not one has returned to their previous health, and most are unable to do their normal activities.”

The consequences of long covid in children can be debilitating. At a UK parliamentary briefing on 26 January, Mcfarland described how her 14-year-old daughter started to become vacant, weak and unresponsive after catching covid-19 in March 2020. After three weeks in bed, she did some gentle exercise in the garden and clutched her chest, complaining of heart pain. “She went very floppy and almost couldn’t make it back into the house to bed,” says Mcfarland. “And she pretty much stayed there [in bed] for the next seven months.”

She went very floppy and almost couldn’t make it back to bed. She stayed there for seven months

Since August 2020, Mcfarland says there have been times where her daughter would feel better and they would go out of the house for a picnic, but they soon realised that every trip out triggered a long period of relapse, an issue that seems to be common in adults with long covid too.

Other cases seem to present very differently. Charlie Mountford-Hill has five children, all of whom have long covid after contracting the virus in the early stages of the pandemic. Almost a year after catching covid-19, her 4-year-old still has a sore neck, lethargy, stomach problems and headaches. Her 10-year-old has fatigue and gastric problems with pain around his heart. “Although they have bad periods and better periods, they are never well,” says Mountford-Hill.

Seeking long-covid care

A common frustration among parents is the lack of support from doctors. Mcfarland says they can dismiss the symptoms as not being related to covid-19 because they are so varied. Often, blood tests and scans also fail to supply any answers. “The majority of people known to Long Covid Kids have been unable to get support,” she says. The group is now working with NHS England to try to get access to care.

Several parents gave evidence at the parliamentary briefing on long covid in children, run by MP Layla Moran. She told New Scientist that the “lack of support, acknowledgement and treatment of long covid in children is a national scandal”. In a letter to the Prime Minister that was shown to New Scientist, several MPs refer to the situation as a crisis that needs to be taken more seriously.

The lack of information on long covid in children is especially pertinent to decisions around schools reopening, as they are due to do in parts of the UK and the US in the coming weeks.

500,000 Children in the UK who have tested positive for covid-19

“We certainly don’t have enough data on the long-term impacts of covid in children to make good policy decisions right now,” says Lambert, who is director of research for Survivor Corps, the largest covid-19 advocacy group in the world. On 18 February, the UK’s National Institute for Health Research awarded £1.4 million for a study to assess risk factors and prevalence of long covid in children.

Nurseries have been allowed to stay open in England while primary and secondary schools have remained shut since 5 January. When asked on 5 February whether the impact of long covid in children has been considered in relation to the reopening of schools, the UK Department for Education gave no reply.

12.9% Percentage of UK children aged 2 to 11 who still have covid-19 symptoms five weeks after initial infection

Sending thousands of children back to school is “insane”, says McFarland. “Sending children back to school seems to be inviting the possibility of giving a whole generation long-term chronic health issues. Why take the risk of opening schools before children have been vaccinated?”

14.5% Percentage of UK children aged 12 to 16 who still have covid-19 symptoms five weeks after initial infection

So far, no coronavirus vaccines have been approved for use in children, although CanSino Biologics in China is testing one in 6 to 12-year-olds, according to data revealed at a recent New York Academy of Science meeting. CEO Xuefeng Yu says that preliminary data will be analysed soon. US company Codagenix is also planning to test a nasal vaccine in children.

The good news is that evidence suggests children don’t easily pass covid-19 to each other in the classroom. In one study, a 9-year-old in France with flu and covid-19 was found to have exposed more than 80 other children at three different schools. However, no one became infected with covid-19 as a result, despite numerous flu infections within the schools, suggesting that although the environment was conducive to transmitting respiratory viruses, covid-19 wasn’t passed on as easily.

More recently, a study of children between 5 months and 4 years old in nurseries in France has shown low levels of infection and transmission of covid-19. The study also shows that staff weren’t at greater risk of infection than a control group of adults. The results suggest that children are more likely to get covid-19 from family members than from their peers or teachers at nursery, although more evidence is needed, say the study’s authors, because the study happened when strict measures were in place to control the virus, and before fast-spreading variants appeared.

Until now, the focus of the pandemic has been on preventing severe disease and deaths in the older generations, but Mcfarland says thoughts need to turn to the legacy the virus is leaving on children.

Study: Myocarditis risk 37 times higher for children with COVID-19 than uninfected peers

Authors: Melissa Jenco, News Content Editor August 31, 2021

The risk of myocarditis for children under 16 years is 37 times higher for those infected with COVID-19 than those who haven’t been infected with the virus, according to a new study.

Authors from the Centers for Disease Control and Prevention (CDC) said the study provides more evidence that the benefits of the vaccine outweigh a small risk of myocarditis after vaccination.

Researchers analyzed data from more than 900 hospitals and found inpatient visits for myocarditis were 42% higher in 2020 compared to 2019, according to a new Morbidity and Mortality Weekly Report.

Among 36 million patients, about 0.01% had myocarditis between March 2020 and February 2021. The median age of people with myocarditis was 54 years, and 59% were male.

About 42% of patients with myocarditis had a history of COVID-19, mostly within the same month. The team determined the risk of myocarditis to be 0.146% among those with COVID-19 and 0.009% among those not diagnosed with COVID-19.

Across all ages, the risk of myocarditis was almost 16 times higher for people with COVID-19 compared to those who aren’t infected. The myocarditis risk is 37 times higher for infected children under 16 years and seven times higher for infected people ages 16-39 compared to their uninfected peers.

Some of the myocarditis cases seen in children with COVID-19 may be cases of multisystem inflammatory syndrome, according to the study.

Authors noted the study could not prove COVID-19 causes myocarditis, but the findings of a link between the two are consistent with several other studies.

In recent months, there has been concern about a small risk of myocarditis after receiving an mRNA COVID-19 vaccine. A June study showed among males ages 12-29 years — the group with the highest rates of myocarditis after vaccination — there would be an estimated 39 to 47 cases of myocarditis for every million second doses of vaccine. Authors of the new study say their findings support health officials’ assertions that the benefits of vaccination outweigh the risks.

“These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications,” they wrote.Resources

Copyright © 2021 American Academy of Pediatrics

Why are we vaccinating children against COVID-19?

Authors: Ronald N.Kostoffa DanielaCalinab DarjaKanducc Michael B.Briggsd Panayiotis Vlachoyiannopoulose Andrey A.Svistunovf AristidisTsatsakisg

Highlights

• Bulk of COVID-19 per capita deaths occur in elderly with high comorbidities.

•Per capita COVID-19 deaths are negligible in children.

•Clinical trials for these inoculations were very short-term.

•Clinical trials did not address long-term effects most relevant to children.

•High post-inoculation deaths reported in VAERS (very short-term).

Abstract

This article examines issues related to COVID-19 inoculations for children. The bulk of the official COVID-19-attributed deaths per capita occur in the elderly with high comorbidities, and the COVID-19 attributed deaths per capita are negligible in children. The bulk of the normalized post-inoculation deaths also occur in the elderly with high comorbidities, while the normalized post-inoculation deaths are small, but not negligible, in children. Clinical trials for these inoculations were very short-term (a few months), had samples not representative of the total population, and for adolescents/children, had poor predictive power because of their small size. Further, the clinical trials did not address changes in biomarkers that could serve as early warning indicators of elevated predisposition to serious diseases. Most importantly, the clinical trials did not address long-term effects that, if serious, would be borne by children/adolescents for potentially decades.

A novel best-case scenario cost-benefit analysis showed very conservatively that there are five times the number of deaths attributable to each inoculation vs those attributable to COVID-19 in the most vulnerable 65+ demographic. The risk of death from COVID-19 decreases drastically as age decreases, and the longer-term effects of the inoculations on lower age groups will increase their risk-benefit ratio, perhaps substantially.

Graphical abstract

Keywords

COVID-19SARS-CoV-2InoculationmRNA vaccines Viral vector vaccines Adverse events Vaccine safety

1. Introduction

Currently, we are in the fifteenth month of the WHO-declared global COVID-19 pandemic. Restrictions of different severity are still in effect throughout the world [1]. The global COVID-19 mass inoculation is in its eighth month. As of this writing in mid-June 2021, over 800,000,000 people globally have received at least one dose of the inoculation and roughly half that number have been fully inoculated [2]. In the USA, about 170,000,000 people have received at least one dose and roughly 80 % of that number have been fully inoculated [2].

Also, in the USA, nearly 600,000 deaths have been officially attributed to COVID-19. Almost 5,000 deaths following inoculation have been reported to VAERS by late May 2021; specifically, “Over 285 million doses of COVID-19 vaccines were administered in the United States from December 14, 2020, through May 24, 2021. During this time, VAERS received 4,863 reports of death (0.0017 %) among people who received a COVID-19 vaccine.” [3] (the Vaccine Adverse Events Reporting System (VAERS) is a passive surveillance system managed jointly by the CDC and FDA [3]. Historically, VAERS has been shown to report about 1% of actual vaccine/inoculation adverse events [4]. See Appendix 1 for a first-principles confirmation of that result). By mid-June, deaths following COVID-19 inoculations had reached the ˜6000 levels.

A vaccine is legally defined as any substance designed to be administered to a human being for the prevention of one or more diseases [5]. For example, a January 2000 patent application that defined vaccines as “compositions or mixtures that when introduced into the circulatory system of an animal will evoke a protective response to a pathogen.” was rejected by the U.S. Patent Office because “The immune response produced by a vaccine must be more than merely some immune response but must be protective. As noted in the previous Office Action, the art recognizes the term “vaccine” to be a compound which prevents infection” [6]. In the remainder of this article, we use the term ‘inoculated’ rather than vaccinated, because the injected material in the present COVID-19 inoculations prevents neither viral infection nor transmission. Since its main function in practice appears to be symptom suppression, it is operationally a “treatment”.

In the USA, inoculations were administered on a priority basis. Initially, first responders and frontline health workers, as well as the frailest elderly, had the highest priority. Then the campaign became more inclusive of lower age groups. Currently, approval has been granted for inoculation administration to the 12–17 years demographic, and the target for this demographic is to achieve the largest number of inoculations possible by the start of school in the Fall. The schedule for inoculation administration to the 5–11 years demographic has been accelerated to start somewhere in the second half of 2021, and there is the possibility that infants as young as six months may begin to get inoculated before the end of 2021 [7].

The remainder of this article will focus on the USA situation, and address mainly the pros and cons of inoculating children under eighteen. The article is structured as follows:

Section 1 (the present section) introduces the problem.

Section 2 (Background):1) provides the background for the declared COVID-19 “pandemic” that led to the present inoculations;2) describes the clinical trials that provided the justification for obtaining Emergency Use Authorization (EUA) from the FDA to administer the inoculations to the larger population;3)

shows why the clinical trials did not predict either the seriousness of adverse events that have occurred so far (as reported in VAERS) or the potential extent of the underlying pre-symptomatic damage that has occurred as a result of the inoculations.

Section 3 (Mass Inoculation) summarizes the adverse events that have occurred already (through reporting in VAERS) from the mass inoculation and will present biological evidence to support the potential occurrence of many more adverse effects from these inoculations in the mid-and long-term.

Section 4 (Discussion) addresses these effects further

Section 5 (Summary and Conclusions) presents the conclusions of this study.

There are four appendices to this paper.

Appendix A provides some idea of the level of under-reporting of post-inoculation adverse events to VAERS and presents estimations of the actual number of post-inoculation deaths based on extrapolating the VAERS results to real-world experiences.

Appendix B provides a detailed analysis of the major clinical trials that were used to justify EUA for the inoculants presently being administered in the USA.

Appendix C summarizes potential adverse effects shown to have resulted from past vaccines, all of which could potentially occur as a result of the present inoculations.

Appendix D presents a novel best-case scenario cost-benefit analysis of the COVID-19 inoculations that have been administered in the USA.

2. Background

2.1. Pandemic history

In December 2019, a viral outbreak was reported in Wuhan, China, and the responsible coronavirus was termed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [8,9]. The associated disease was called Coronavirus Disease 2019, or COVID-2019. The virus spread worldwide, and a global pandemic was declared by the WHO in March 2020 [10,11]. Restrictive measures of differing severity were implemented by countries globally, and included social distancing, quarantining, face masks, frequent hand sanitation, etc. [12,13]. In the USA, these measures were taken as well, differing from state-to-state [14]. At the same time, vaccine development was initiated to control COVID-19 [15]. In the USA, non-vaccine treatments were not encouraged at the Federal level, but different treatment regimens were pursued by some healthcare practitioners on an individual level [11,16,17].

By the end of May 2021, the official CDC death count attributed to COVID-19 was approaching 600,000, as stated previously. This number has been disputed for many reasons. First, before COVID-19 testing began, or in the absence of testing, after it was available, the diagnosis of COVID-19 (in the USA) could be made by the presumption of the healthcare practitioner that COVID-19 existed [4,18]. Second, after testing began, the main diagnostic used was the RT-PCR test. This test was done at very high amplification cycles, ranging up to 45 [[19][20][21]]. In this range, very high numbers of false positives are possible [22].

Third, most deaths attributed to COVID-19 were elderly with high comorbidities [1,22]. As we showed in a previous study [22], attribution of death to one of many possible comorbidities or especially toxic exposures in combinations [23] is highly arbitrary and can be viewed as a political decision more than a medical decision. For over 5 % of these deaths, COVID-19 was the only cause mentioned on the death certificate. For deaths with conditions or causes in addition to COVID-19, on average, there were 4.0 additional conditions or causes per death [24]. These deaths with comorbidities could equally have been ascribed to any of the comorbidities [22]. Thus, the actual number of COVID-19-based deaths in the USA may have been on the order of 35,000 or less, characteristic of a mild flu season.

Even the 35,000 deaths may be an overestimate. Comorbidities were based on the clinical definition of specific diseases, using threshold biomarker levels and relevant symptoms for the disease(s) of interest [25,26]. But many people have what are known as pre-clinical conditions. The biomarkers have not reached the threshold level for official disease diagnosis, but their abnormality reflects some degree of underlying dysfunction. The immune system response (including pre-clinical conditions) to the COVID-19 viral trigger should not be expected to be the same as the response of a healthy immune system [27]. If pre-clinical conditions had been taken into account and coupled with the false positives as well, the CDC estimate of 94 % misdiagnosis would be substantially higher.

2.2. Clinical trials

2.2.1. Clinical trials to gain FDA Emergency Use Authorization (EUA) approval

The unprecedented accelerated development of COVID-19 vaccines in the USA, dubbed Operation Warp Speed, resulted in a handful of substances available for clinical trials by mid-2020 [28]. These clinical trials were conducted to predict the safety and efficacy of the potential vaccines (which have turned out to be treatments/inoculations as stated previously), and thereby gain approval for inoculating the public at large [29]. An overview of the Pfizer clinical trials is presented in this section, and a more detailed description of the main clinical trials is shown in Appendix B.

Two types of inoculants have gained FDA EUA in the US: mRNA-based inoculants and viral vector-based inoculants, with the mRNA inoculants having the widest distribution so far. Comirnaty is the brand name of the mRNA-based inoculant developed by Pfizer/BioNTech, and Moderna COVID-19 Vaccine is the brand name of the mRNA-based inoculant developed by Moderna [30]. Both inoculants contain the genetic information needed for the production of the viral protein S (spike), which stimulates the development of a protective immune response against COVID-19 [31]. Janssen COVID-19 Vaccine is the brand name of the viral vector-based inoculant developed by Johnson and Johnson. Janssen COVID-19 vaccine uses an adenovirus to transport a gene from the coronavirus into human cells, which then produce the coronavirus spike protein. This spike protein primes the immune system to fight off potential coronavirus infection [32].

The results of these trials that allowed granting of EUA by the FDA can be found in the inserts to the inoculation materials. For example, the Pfizer inoculation trial results are contained in the fact sheet for healthcare providers administering vaccine (vaccination providers) [33].

There were two clinical trials conducted to gain FDA EUA for Pfizer: a smaller Phase 1/2 study, and a larger Phase 1/2/3 study. The age demographics for the larger clinical study are as follows (from the Pfizer insert): “Of the total number of Pfizer-BioNTech COVID-19 Vaccine recipients in Study 2 (N = 20,033), 21.4 % (n = 4,294) were 65 years of age and older and 4.3 % (n = 860) were 75 years of age and older.” Additionally: “In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 adolescents (1,131 Pfizer-BioNTech COVID-19 Vaccine; 1,129 placebo) were 12 through 15 years of age. Of these, 1,308 (660 Pfizer-BioNTech COVID-19 Vaccine and 648 placebo) adolescents have been followed for at least 2 months after the second dose of Pfizer-BioNTech COVID-19 Vaccine. The safety evaluation in Study 2 is ongoing.”

The relevant demographics are presented in Table 7 on p.31 of the Pfizer insert. The age component of those demographics is shown below in Table 1.

Table 1. Demographics (population for the primary efficacy endpoint). The number of participants who received vaccine and placebo, stratified by age.

AGE GROUPPfizer-BioNTech COVID-19 Vaccine (N = 18,242) n (%)Placebo (N = 18,379)
n (%)
≥12 through 15 yearsb46 (0.3 %)42 (0.2 %)
≥16 through 17 years66 (0.4 %)68 (0.4 %)
≥16 through 64 years14,216 (77.9 %)14,299 (77.8 %)
≥65 through 74 years3176 (17.4 %)3226 (17.6 %)
≥75 years804 (4.4 %)812 (4.4 %)

Symbols: b: “100 participants 12 through 15 years of age with limited follow-up in the randomized population received at least one dose (49 in the vaccine group and 51 in the placebo group). Some of these participants were included in the efficacy evaluation depending on the population analyzed. They contributed to exposure information but with no confirmed COVID-19 cases, and did not affect efficacy conclusions.”, N: number of test subjects, n: number of controls.

There are very minor differences between most of the data in the above table and the preceding narrative shown, and they are probably due to different time horizons. The major difference is the number of adolescents used and appears to result from a much later reporting time.

Fig. 1 uses the official large CDC numbers (coupled with USA census data estimates from CDC Wonder) to show the COVID-19 deaths per capita as a function of age, circa early June 2021. Unfortunately, the most critical range, 85+, has the least resolution. It is obvious that most of the deaths occurred in the 55 to 100+ range, and the remaining individuals in the other ranges (especially under 35) have negligible risk of dying from the disease.

Fig. 1

The age distribution in Fig. 1 differs substantially from the age distribution in Table 1. Why is this important? When designing a trial for the efficacy and safety of a potential treatment, the focus should be on the target population who could benefit from that treatment. There is little rationale for including participants in a trial for whom the treatment would not be relevant or warranted.

For the COVID-19 Pfizer trials, based on the data from Fig. 1, the trial population should have been limited at most to the 45−100+ age segment, appropriately weighted toward the higher end where the deaths per capita are most frequent. That was almost the exact opposite of what was done in the Pfizer clinical trials. In Fig. 1, approximately 58 % of the deaths occurred in the age range 75+, whereas 4.4 % of the participants in the Pfizer clinical trial were 75 + . Thus, the age range most impacted by COVID-19 deaths was minimally represented in the Pfizer clinical trials, and the age range least impacted by COVID-19 deaths was maximally represented in the Pfizer clinical trials. This skewed sampling has major implications for predicting the expected numbers of deaths for the target population from the clinical trials.

Besides age, the other metric of importance in determining COVID-19 deaths is the presence of comorbidities. The more comorbidities, and the more severe the comorbidities, the greater the chances of death or severe adverse outcomes from COVID-19. It is not clear how well the number and severity of comorbidities in the clinical trial sample matched those reflected in Fig. 1, but the insert does mention the large number of conditions that excluded participation in the trials. In sum, the results from the clinical trials could not be expected to reflect the results that could occur (and have occurred) from mass inoculation of the public, given the unaffected nature of the bulk of the trial population from SARS-CoV-2 exposure.

The prior discussion on the clinical trials has focused on the efficacy and safety of the inoculants, and the relationship of the trial test population to the total target population. We have limited the focus so far to the safety and efficacy issues since these constituted the core of what was presented to the FDA for EUA approval. We have not focused on the trials from an early warning indicator perspective.

We will address summarily the science/early warning indicator issues associated with the Pfizer trials, and how the neglect of these issues has translated into disastrous consequences during the mass inoculation rollout. Standard practice for determining and understanding the impact of new technology (such as mRNA “vaccines”) on a system involves measuring the state and flux variables of the system before the new technology intervention, measuring the state and flux variables of the system after the new technology intervention, and identifying the types and magnitudes of changes in the state and flux variables attributable to the intervention. This would be in addition to evaluating performance metrics before and after the intervention.

In Pfizer’s proposed clinical trials for the mRNA “vaccine” (Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in Healthy Individuals – https://clinicaltrials.gov/ct2/show/NCT04368728), the focus was on determining 1) adverse events/symptoms, 2) SARS-CoV-2 serum neutralizing antibody levels, 3) SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, and 4) effectiveness. These metrics are all related to safety at the symptom level and performance.

However, symptoms/diseases are typically end points of processes that can take months, years, or decades to surface. During that symptom/disease development period, many biomarker early warning indicators tend to exhibit increasing abnormalities that reflect an increasing predisposition to the eventual symptom/disease. Thus, serious symptoms/diseases that ordinarily take long periods to develop would be expected to be rare events if they occurred shortly following an inoculation. If the clinical trials that were performed by Pfizer and Moderna were designed to focus on efficacy and only adverse effects at the symptom level of description as an indicator of safety, the trial results would be limited to the identification of rare events, and the trial results would potentially under-estimate the actual pre-symptom level damage from the inoculations.

Credible safety science applied to this experiment would have required a much more expansive approach to determining effects on a wide variety of state and flux metrics that could serve as early warning indicators of potentially serious symptoms/disease, and might occur with much higher frequencies at this early stage than the rare serious symptoms. The only mention of these other metrics in the above proposal is in the Phase I trial description: “Percentage of Phase 1 participants with abnormal haematology and chemistry laboratory values”, to be generated seven days after dose 1 and dose 2.

A paper published in NEJM in December 2020 [34] summarized the Phase 1 results. The focus was on local and systemic adverse events and efficacy metrics (antibody responses). The only metrics other than these reported were transiently decreased lymphocyte counts.

We view this level of reporting as poor safety science for the following reasons. Before the clinical trials had started, many published articles were reporting serious effects associated with the presence of the SARS-CoV-2 virus such as hyperinflammation, hypercoagulation, hypoxia, etc. SARS-CoV-2 includes the S1 Subunit (spike protein), and it was not known how much of the damage was associated with the spike protein component of SARS-CoV-2. A credible high-quality safety science experiment would have required state measurements of specific biomarkers associated with each of these abnormal general biomarkers before and after the inoculations, such as d-dimers for evidence of enhanced coagulation/clotting; CRP for evidence of enhanced inflammation; troponins for evidence of cardiac damage; occludin and claudin for evidence of enhanced barrier permeability; blood oxygen levels for evidence of enhanced hypoxia; amyloid-beta and phosphorylated tau for evidence of increased predisposition to Alzheimer’s disease; Serum HMGB1, CXCL13, Dickkopf-1 for evidence of an increased disposition to autoimmune disease, etc. A credible high-quality safety science experiment would have required flux measurements of products resulting from the mRNA interactions, from the LNP shell interactions, from dormant viruses that might have been stimulated by the mRNA-generated spike protein, etc., emitted through the sweat glands, faeces, saliva, exhalation, etc.

Most importantly, these types of measurements would have shown changes in the host that did not reach the symptom level of expression but raised the general level of host abnormality that could predispose the host to a higher probability of serious symptoms and diseases at some point in the future. Instead, in the absence of high-quality safety science reflected in these experiments, all that could be determined were short-term adverse effects and deaths. This focus on symptoms masked the true costs of the mRNA intervention, which would probably include much larger numbers of people whose health could have been degraded by the intervention as evidenced by increased abnormal values of these biomarkers. For example, the trials and VAERS reported clots that resulted in serious symptoms and deaths but gave no indication of the enhanced predisposition to forming serious clots in the future with a higher base of micro-clots formed because of the mRNA intervention. The latter is particularly relevant to children, who have a long future that could be seriously affected by having an increased predisposition to multiple clot-based (and other) serious diseases resulting from these inoculations.

3. Mass inoculation

3.1. Adverse events reported for adults

This section describes the adverse effects that followed COVID-19 mass inoculation in the USA. The main source of adverse effects data used was VAERS. Because VAERS is used to estimate adverse event information by many other countries as well, a short overview of VAERS and its intrinsic problems is summarized in Appendix 1.

The period in the present study covered by the reported inoculations is mid-December 2020 to the end of May 2021. The population inoculated during this period is mainly adults. Child inoculations did not begin until mid-May. Because the different age groups were inoculated starting at different times based on priority, the elapsed times after inoculation will be different, and any adverse event comparisons across age groups will require some type of elapsed post-inoculation time normalization.

We examined VAERS-reported deaths by age group, normalized to:1)

the number of inoculations given2)

the period within seven days after inoculation.

This allows a credible comparison of very short-term adverse effects post-inoculation for all age groups. During this period, which is eight days post-inoculation (where day zero is the day of inoculation), ˜sixty percent of all post-inoculation deaths are reported in VAERS.

Fig. 2 below shows the results circa late May 2021 [3]. The age band ranges are different from those in Fig. 1 because the CDC provides inoculation after-effect age bands differently from COVID-19 death age bands. In general, the inoculation deaths by age per inoculant roughly parallel the COVID-19 deaths by age per capita (the curve structures are very similar), with one exception: the 0–17 demographic. In the normalized COVID-19 death graph (Fig. 1), the deaths per capita in the 0–17 demographic are negligible, while in the normalized inoculant death graphs (Fig. 2) the normalized deaths are small, but not negligible. The members of the 65+ demographic, where the bulk of deaths are occurring in Fig. 1Fig. 2, have been receiving inoculations for ˜five months, whereas the members of the youngest demographic have been receiving inoculations only for a few weeks. More time needs to pass before more definitive conclusions can be drawn about the youngest demographic, and how its members are impacted adversely following the inoculations.

Fig. 2

The high death rates from both COVID-19 and the inoculations in the 65+ demographic should not be surprising. In both cases, the immune system is challenged, and in both cases, a dysfunctional immune system characteristic of many elderly people with multiple comorbidities cannot respond adequately to the challenge.

3.1.1. Specific short-term adverse events reported in VAERS

The most comprehensive single evaluation of VAERS-reported adverse events (mainly for adult recipients of the COVID-19 “vaccines”) we have seen is a non-peer-reviewed collection of possible side effects by Dr. Ray Sahelian [35]. We recommend reading this short data-rich summary of the broad types of events reported already, in the context that these events are very short-term. Dr. Sahelian identifies five mechanisms he believes are responsible for most of these events, with research potentially uncovering other mechanisms. These five mechanisms include:1

“An overreacting inflammatory response is known as systemic inflammatory response syndrome (SIRS). This SIRS reaction, perhaps a cytokine storm, can range from very mild to very severe. It can begin the very first day of the shot or begin days or weeks later as a delayed reaction.”2

“Interaction of the spike proteins with ACE2 receptors on cell membranes. Such cells are found widely in the body including the skin, lungs, blood vessels, heart, mouth, gastrointestinal tract, kidneys, and brain.”3

“Interaction of spike proteins with platelets and/or endothelial cells that line the inside of blood vessels. This can lead to clotting or bleeding (low number of circulating platelets in the bloodstream). Some of the clots, even if tiny, cause certain neurological symptoms if the blood supply to nerves is compromised.”4

“Immediate or delayed release of histamine from mast cells and basophils (mast cell activation syndrome, MCAS).”5

5. “Swelling of lymph nodes in various areas of the body could interfere with blood flow, put pressure on nerves causing pain, or compromise their proper function.”

These reactions can be classified as Hyperinflammation, Hypercoagulation, Allergy, and Neurological, and can contribute to many symptoms and diseases, as VAERS is showing.

An excellent review of acute and potential long-term pathologies resulting from the COVID-19 inoculations [36] showed potential relationships to blood disordersneurodegenerative diseases and autoimmune diseases. This review discussed the relevance of prion-protein-related amino acid sequences within the spike protein.

3.1.2. Potential mid- and long-term events and serious illnesses for adults and children from past vaccines

A detailed description of potential mid- and long-term events and serious illnesses for adults and children from past vaccines is presented in Appendix C. Most of these events and illnesses are not predictable, and most, if not all, would be possible for the COVID-19 inoculations in the mid- and long-term for adults and children.

3.1.3. Potential short-, mid-, and long-term risks of mass COVID-19 inoculation for children

3.1.3.1. Intrinsic inoculant toxicity

Children are unique relative to COVID-19. They have negligible risks of serious effects from the disease, as shown in Fig. 1. Given that the COVID-19 inoculants were only tested for a few months, and mid-or long-term adverse effects are unknown, any mid- or long-term adverse events that emerge could impact children adversely for decades.

We believe that mid-or long-term adverse effects are possible based on the recent emergence of evidence that would support the probability of mid-and long-term adverse effects from the COVID-19 inoculants, such as:1)

The spike protein itself can be a toxin/pathogenic protein:2)

S protein alone can damage vascular endothelial cells (ECs) by downregulating ACE2 and consequently inhibiting mitochondrial function [37].3)

it is concluded that ACE2 and endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone [38].4)

the spike protein of SARS-CoV-1 (without the rest of the virus) reduces ACE2 expression, increases angiotensin II levels, exacerbates lung injury, and triggers cell signaling events that may promote pulmonary vascular remodeling and Pulmonary Arterial Hypertension (PAH) as well as possibly other cardiovascular complications [39].5)

the recombinant S protein alone elicits functional alterations in cardiac vascular pericytes (PCs) [40]. This was documented as:6)

increased migration7)

reduced ability to support EC network formation on Matrigel8)

secretion of pro-inflammatory molecules typically involved in the cytokine storm9)

production of pro-apoptotic factors responsible for EC death. Furthermore, the S protein stimulates the phosphorylation/activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) through the CD147 receptor, but not ACE2, in cardiac PCs, the S protein may elicit vascular cell dysfunction, potentially amplifying, or perpetuating, the damage caused by the whole coronavirus [40].10)

“even in the absence of the angiotensin-converting enzyme 2 receptors, the S1 subunit from SARS-CoV-2 spike protein binding to neutral phospholipid membranes leads to their mechanical destabilization and permeabilization. A similar cytotoxic effect of the protein was seen in human lung epithelial cells.” [125].11)

The LNP layer encapsulating the mRNA of the inoculant is highly inflammatory in both intradermal and intranasal inoculation [41] and “Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine” [42]. “Humans are likely developing PEG antibodies because of exposure to everyday products containing PEG. Therefore, some of the immediate allergic responses observed with the first shot of mRNA-LNP vaccines might be related to pre-existing PEG antibodies. Since these vaccines often require a booster shot, anti-PEG antibody formation is expected after the first shot. Thus, the allergic events are likely to increase upon re-vaccination” [43].

There is also the possibility that the components of the LNP shell could induce the ASIA Syndrome (autoimmune/inflammatory syndrome induced by adjuvants), as shown by studies on post-inoculation thyroid hyperactivity [44] and post-inoculation subacute thyroiditis [45].12

The spike protein has been found in the plasma of post-inoculation individuals, implying that it could circulate to, and impact adversely, any part of the body [46].13

The spike protein of SARS-CoV-2 crosses the blood-brain barrier in mice [47], and “the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function” [48].14

The spike proteins manufactured in vivo by the present COVID-19 inoculations could potentially “precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases”, based on the finding that anti-SARS-CoV-2 protein antibodies cross-reacted with 28 of 55 diverse human tissue antigens [49].15

“The biodistribution of ChaAdOx1 [Astra Zeneca’s recombinant adenovirus vaccine candidate against SARS-CoV-2] in mice confirmed the delivery of vaccine into the brain tissues [50]. The vaccine may therefore spur the brain cells to produce CoViD spike proteins that may lead to an immune response against brain cells, or it may spark a spike protein-induced thrombosis. This may explain the peculiar incidences of the fatal cerebral venous sinus thrombosis (CVST) observed with viral vector-based CoViD-19 vaccines” [51,52].

A complementary perspective to explain adenovirus-based vaccine-induced thrombocytopenia is that “transcription of wildtype and codon-optimized Spike open reading frames enables alternative splice events that lead to C-terminal truncated, soluble Spike protein variants. These soluble Spike variants may initiate severe side effects when binding to ACE2-expressing endothelial cells in blood vessels.” [100].16

A Pfizer Confidential study performed in Japan showed that “modRNA encoding luciferase formulated in LNP comparable to BNT162b2″ injected intramuscularly concentrated in many organs/tissues in addition to the injection site [53]. The main organs/sites identified were adrenal glands, liver, spleen, bone marrow, and ovaries. While damage to any of these organs/sites could be serious (if real for humans), adverse effects on the ovaries could be potentially catastrophic for women of childbearing or pre-childbearing age.

The main objective of credible biodistribution studies (of inoculants for eventual human use) is to identify the spatio-temporal distribution of the actual inoculant in humans; i.e., how much of the final desired product (in this case, expressed protein antigen/spike protein) is produced in different human tissues and organs as a function of time. That’s not what was reported in the Pfizer Confidential study.

Rats were used for the in vivo studies; the relationship of their biodistribution to that of humans is unclear. They were injected in different locations (hindpaw/intramuscular); the relationship to human injections in the deltoid muscle is unclear. They were injected with “modRNA encoding luciferase formulated in LNP comparable to BNT162b2″; it is unclear why they weren’t injected with BNT162b2, it is unclear why spike protein expression wasn’t evaluated rather than LNP concentration, and it is unclear how well the biodistribution from the actual inoculant used in the experiments compares to the biodistribution from BNT162b2.

They were injected once per rat. Given that a second injection would not be in the same exact location as the first, and that the circulatory system might have changed due to clotting effects from the first injection and other potential vascular complications, it is unclear how the biodistribution change with the second injection would compare with the first. If a booster injection is given to counter variants, it is unclear how its biodistribution would be altered as a consequence of the preceding two injections.

Clotting will occur with the highest probability where the blood flow is reduced (and more time is available for LNP-endothelial cell interaction). It is unclear whether the clotting process would show positive feedback behaviour where the initial inoculation constricts the flow in low-velocity regions even further by enhanced clotting, and subsequent inoculations further amplify this reduced flow-enhanced clotting cycle.

The rats were injected under pristine conditions; how that compares with humans, who have been, are being, and will continue to be exposed to multiple toxic substances in combination, is open to question. We know these combinations can act synergistically to adversely impact myriad organs and tissues throughout the body [23]. We don’t know how these toxic exposures in humans affect the permeability of the blood/tissue barriers, and especially the ability of the injected material to diffuse into the bloodstream (and also the ability of the manufactured spike proteins to diffuse from the bloodstream into the surrounding tissue).

Higher-level primates should have been used for these short-term experiments, to obtain a more realistic picture of the biodistribution of inoculant in human organs and tissues. In other words, these laboratory experiments may be just the tip of the iceberg of estimating the amount of inoculant that concentrates in critical organs and tissues of human beings.

The many studies referenced above indicate collectively that the mRNA-based COVID-19 inoculations (the most prolific inoculations used in the USA for COVID-19 so far) consist of (at least) two major toxins: the instructions for the spike protein (mRNA) and the mRNA-encapsulating synthetic fat LNP. The vaccine is injected into the deltoid muscle, at which time it contributes to inflammation at the injection site due in part to the LNP and potentially to anaphylaxis from the LNP PEG-2000 component. Some of the injected material stays at the injection site, where it combines with cells through endocytosis to express spike protein on the cell surface, stimulating the adaptive immune system to eventually produce antibodies to the spike protein [54].

The remainder of the injected material enters the lymphatic system and the bloodstream, and is distributed to tissues and organs throughout the body: e.g., “Drugs administered by the intramuscular (IM) route are deposited into vascular muscle tissue, which allows for rapid absorption into the circulation” [55]. The basis of this process is that the bulky muscles have good vascularity, and therefore the injected drug quickly reaches the systemic circulation and thereafter into the specific region of action, bypassing the first-pass metabolism [56]. The widespread distribution is greatly enhanced by the LNP PEG-2000 coating as follows: building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity [57]. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. [57]. PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration. [57]

In the bloodstream, one possible outcome is that the LNPs coalesce with the endothelial cells on the inner lining of the blood vessels and transfer the mRNA to the cells through endocytosis. The endothelial cells would then express the spike protein on their surface. Platelets flowing by the spike protein express ACE2 receptors on their surface; therefore, one possible outcome would be activation of the platelets by the spike protein and initiation of clotting. Another possible outcome would be the modified endothelial cells being recognized by innate immune system cells as foreign. These immune killer cells would then destroy parts of the endothelium and weaken the blood-organ barriers. The LNPs would inflame the endothelium as well, both increasing barrier permeability and increasing the blood vessel diameter. This weakening of the blood-organ barriers would be superimposed on any inflammation due to the myriad toxic contributing factors operable [4]. The newly-formed cells with spike proteins would penetrate the blood-organ barriers and bind to tissue with expressed ACE2 receptors. Any LNPs that did not coalesce with the endothelial cells, but remained intact, could also pass through the permeable blood-organ barrier, and coalesce directly with the organ cells. This could lead to an attack by innate immune system cells, and be a precursor to autoimmunity [4].

In the preceding discussion of the Pfizer biodistribution studies, the issue of multiple inoculations on changes in biodistribution was raised. Similarly, the alteration of effects as described above by multiple inoculations must be considered. Each inoculation will have positive aspects and negative aspects. The positive aspects are the formation of antibodies in the muscle cells and lymphatic system. The negative aspects include, but are not limited to, the potential clotting effects and permeability increases for that fraction of the inoculant that enters the bloodstream. The first inoculant dose can be viewed as priming the immune system. The immune response will be relatively modest. The second inoculant dose can be expected to elicit a more vigorous immune response. This will enhance the desired antibody production in the muscle cells and lymphatic system, but may also enhance the immune response to both the blood vessel-lining endothelial cells displaying the spike protein and the platelets, causing more severe damage. If a booster(s) inoculation is also required, this may further enhance both the positive and negative immune responses resulting from the second inoculation. While the positive effects are reversible (antibody levels decrease with time), adverse effects may be cumulative and irreversible, and therefore injury and death rates may increase with every additional inoculation [58].

These effects can occur throughout the body in the short term, as we are seeing with the VAERS results. They can occur in the mid- and long-term as well, due to the time required for destructive processes to have full effect and the administration of further inoculations. For example, micro-clots resulting from the inoculation that were insufficient to cause observable symptoms could in effect raise the baseline for thrombotic disease [92]. Lifestyle activities that contribute to enhanced blood clotting would have less distance to travel to produce observable symptoms, and thus the serious effects of clotting would have been accelerated [59,60]. As an example: the risk of venous thrombosis is approximately 2- to 4-fold increased after air travel [61]. How much this rate would increase after the inoculations, where microthrombi have formed in some recipients, is unknown. These potential baseline-raising effects could impact the interpretation of the VAERS results, as we show at the end of Appendix 1.

3.1.3.2. Adverse inoculant effects on children

What are the potential mid- and long-term adverse health effects from the COVID-19 inoculation on children specifically, taking into account that they will be exposed not only to the spike protein component of the SARS-CoV-2 virus but also to the toxic LNP encapsulating-shell? This toxic combination will have bypassed many defensive safeguards (typically provided by the innate immune system) through direct injection [62]. As we have shown, the main reasons why we believe the spike protein could be harmful to children even though they don’t seem to get sick from exposure to SARS-CoV-2 are 1) the bypassing of the innate immune system by inoculation, 2) the larger volume of spike protein that enters the bloodstream, and 3) the additional toxic effects of the encapsulating LNP layer.

3.1.3.2.1. Potential mid-term adverse health effects

Examination of the myriad post-COVID-19 inoculation symptoms/biomarker changes for the 0–17 age demographic reported to VAERS circa mid-June 2021 provides some indication of very early damage [84]. Main regions/systems affected adversely (VAERS symptoms/biomarkers shown in parentheses) include:•

Cardiovascular (blood creatine phosphokinase increased, cardiac imaging procedure abnormal, echocardiogram abnormal, electrocardiogram abnormal, heart rate increased, myocarditispalpitationspericarditistachycardiatroponin I increased, troponin increased, fibrin D-Dimer increased, platelet count decreased, blood pressure increased, bradycardiabrain natriuretic peptide increased, ejection fraction decreased, migraine)•

Gastrointestinal (abdominal pain, diarrhoea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased.)•

Neural (gait disturbance, mobility decreased, muscle spasms, muscle twitching, seizure, tremor, Bell’s Palsy, dyskinesia)•

Immune (C-Reactive Protein increased, red blood cell sedimentation rate increased, white blood cell counts increased, inflammation, anaphylactic reaction, pruritis, rash, lymphadenopathy)•

Endocrine (heavy menstrual bleeding, menstrual disorder)

In addition, there were large numbers of different vision and breathing problems reported.

All the major systems of the body are impacted, and many of the major organs as well. Given the lag times in entering data into VAERS and the fact that inoculations of children started fairly recently, we would expect the emphasis to be immediate symptomatic and biomarker reactions. More time is required for organ and system damage to develop and emerge. Cardiovascular problems dominate, as our model for spike protein/LNP circulation and damage predicts, and it is unknown how reversible such problems are. Many of the VAERS symptoms listed above were also found in COVID-19 adult patients [64].

Consider the example of Multisystem Inflammatory Syndrome in Children (MIS-C). It has emerged in VAERS with modest frequency so far, and it also occurred about a month after COVID-19 infection [65]. In both cases, the presence of the spike protein was a common feature. Many of its characteristic symptoms are those listed above from VAERS. MIS-C has similarities with known disease entities like Kawasaki Disease (KD), toxic shock syndrome (TSS) and macrophage activation syndrome (MAS)/secondary hemophagocytic lymphohistiocytosis (HLH) [66]. One presentation of MIS-C is in adolescents with a high disease burden as evidenced by more organ systems involved, almost universally including cardiac and gastrointestinal systems, and with a higher incidence of shock, lymphopenia, and elevated cardiac biomarkers indicating myocarditis [67]. Since the first reports of children developing MIS-C, it was evident that others presented with some of the classic symptoms of the well-recognized childhood illness KD [68]. Further, despite KD being ordinarily incredibly rare in adults, patients with MIS-A have also been reported with KD-like features. [68] Thus, an examination of the adverse effects from COVID-19 as evidenced through these diseases might shed some light on what can be expected further down the line from the inoculations.

The following section addresses Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) [65].

KD is an acute vasculitis and inflammation that predominantly affects the coronary arteries and can cause coronary artery aneurysms. Other KD manifestations include systemic inflammation of arteries, organs, and tissues, with consequent hepatitis and abdominal pain; lung interstitial pneumonitisaseptic meningitis due to brain membrane inflammations; myocarditis, pericarditis, and valvulitis; urinary tract pyuriapancreatitis; and lymph-node enlargement [69]. In general, although almost all children fully recover, some of them later develop coronary artery dilation or aneurysm [70]. Etiologically and pathologically, numerous studies indicate that KD is triggered by an abnormal autoimmune response caused by an infection [71]. The infection hypothesis is supported by epidemiology data showing that an infectious disease is involved at least as a starting point. Previously proposed infectious agents include Herpesviridaeretroviruses, Parvovirus B19, bocavirus, and bacterial infections such as staphylococci, streptococci, Bartonella, and Yersinia infections [72].

SARS-CoV-2 adds to these infectious agents by eliciting autoantibodies likely via molecular mimicry and cross-reactivity with autoantigens [72,73].

Then, the formation of antigen–antibody immune complexes can lead to KD symptoms via activation of the receptors of mast cells, neutrophils, and macrophages with consequent release of pro-inflammatory cytokines and increase of blood vessel permeability; activation of the complement system, stimulation of neutrophils and macrophages to secrete proteases and more proinflammatory cytokines [74], thus merging into the “cytokine storm” that characterizes MIS-C [75]. Indeed, features of KD are raised levels of Interleukin (IL)-6, IL-8, IL-15, and IL-17, with the cytokine level predicting coronary aneurysm formation in KD patients [76,77]

3.1.3.2.2. Potential long-term adverse health effects

In the long-term, SARS-CoV-2-induced KD vasculitis can lead to severe pathologies. Vasculitis has a predilection for coronary arteries with a high complication rate across the lifespan for those with medium to large coronary artery aneurysms [78]. The cytokine-induced inflammation produces endothelial dysfunction and damage to the vascular wall, leading to aneurysmal dilatation. Successively, vascular remodeling can also occur, but this does not imply resolution of the disease or reduction of risk for future complications. A rigorous follow-up to detect progressive stenosis, thrombosis and luminal occlusion that may lead to myocardial ischemia and infarction becomes mandatory [78]. Of equal importance, among other long-term outcomes, children with KD may have increased risks not only for ischemic heart disease, but also for autoimmune disorders, cancer as well as an increased all-cause mortality [71].

Additional questions regarding mass inoculation of children and adolescents include:

a)

Do children, being asymptomatic carriers of SARS-CoV-2, transmit the virus?b)

Do recently vaccinated people, infected with SARS-CoV-2, transmit the virus?

There is evidence of children transmitting SARS-CoV-2 in community settings, but the existing literature is heterogeneous with regards to the relative rate at which they do so compared to adults [79].

Studies from South Korea and Thailand found a very limited number of secondary cases [80,81]. On the contrary, a large contact tracing study from India concluded that the highest probability of transmission was between case-contact pairs of similar age and that this pattern of enhanced transmission risk was highest among children 0–4 years of age as well as adults 65 years of age and older [80]

With regard to the second question, it was shown that household members of healthcare workers inoculated with a single dose of either Pfizer or Astra Zeneca COVID-19 inoculant were at significantly reduced risk of PCR-confirmed SARS-CoV-2 infection but at non-statistically significant reduced risk of hospitalization, compared to household members of uninoculated healthcare workers, fourteen days after inoculation [82]. This finding again underlines the association of severe disease to the characteristics of the infected person and not directly to the transmission, implying that the elderly should be inoculated and not the children.

3.2. Novel best-case scenario cost-benefit analysis of COVID-19 inoculations for most vulnerable

Traditional cost-benefit analyses are typically financial tools used to estimate the potential value of a proposed project. They involve generating cost streams over time, benefit streams over time, and then comparing the net present value of these two streams (including risk) to see whether the risk-adjusted discounted benefits outweigh the risk-adjusted discounted costs. Appendix D presents a detailed non-traditional best-case scenario pseudo-cost-benefit analysis of inoculating people in the 65+ demographic in the USA. In this incarnation of a cost-benefit analysis, the costs are the number of deaths resulting from the inoculations, and the benefits are the lives saved by the inoculations. The time range used was from December 2019 to end-of-May 2021. No discounting was done; an inoculation-based death occurring immediately post-inoculation was given the same importance/weighting as an inoculation-based death months after inoculation.

Why was this non-traditional approach selected for a cost-benefit analysis? In a traditional non-financial cost-benefit analysis relative to inoculations, the adverse events prevented by the inoculations would be compared with the adverse events resulting from the inoculations. Presently, in the USA, definitions, test criteria, and reporting incentives for COVID-19 and its inoculants have shifted over time, and we believe a standard approach could not be performed credibly. Appendix Da presents some of the problems with the COVID-19 diagnostic criteria on which the above statements are based.

In contrast to the pandemic buildup phase, where many who died with COVID-19 were assumed to have died from COVID-19 by the medical community and the CDC, the post-inoculation deaths reported in VAERS are assumed by the CDC to be mostly from causes other than the inoculations. We wanted to use a modified cost-benefit analysis that would have less dependence on arbitrary criteria and subjective judgments.

The approach selected can be viewed as a best-case scenario pseudo-cost-benefit analysis. We assume the inoculations prevent all the deaths truly attributable to COVID-19 (these are the total deaths attributed to COVID-19 officially minus 1) the number of false positives resulting from the PCR tests run at very high amplification cycles and 2) the number of deaths that could have been attributed to one of the many comorbidities that were typical of those who succumbed, as shown in our results section) over the period December 2019 to end-of-May 2021, and relate that number to the deaths truly attributable to the inoculation (from January 2021 to end-of-May 2021) based on our computations in the results section. The results show conservatively that there are five times the number of deaths truly attributable to each inoculation vs those truly attributable to COVID-19 in the 65+ demographic. As age decreases, and the risk for COVID-19 decreases, the cost-benefit increases. Thus, if the best-case scenario looks poor for benefits from the inoculations, any realistic scenario will look very poor. For children the chances of death from COVID-19 are negligible, but the chances of serious damage over their lifetime from the toxic inoculations are not negligible.

4. Discussion

Two issues arise from these results.

First, where is the data justifying inoculation for children, much less most people under forty? It’s not found on Fig. 1, where the most vulnerable are almost exclusively the elderly with many comorbidities [83]. Yet, in the USA, Pfizer has been approved to inoculate children 12–17, and the goal is to accomplish this by the start of the school year in the Fall. As stated previously, there are plans to inoculate children as young as six months starting before the end of 2021.

What is the rush for a group at essentially zero risks? Given that the inoculations were tested only for a few months, only very short-term adverse effects could be obtained. It is questionable how well even these short-term effects obtained from the clinical trials reflect the short-term effects from the initial mass inoculation results reported in VAERS.

Fig. 1Fig. 2 reflect only these very short-term results. A number of researchers have suggested the possibility of severe longer-term autoimmune, Antibody-Dependent Enhancement, neurological, and other potentially serious effects, with lag periods ranging from months to years. If such effects do turn out to be real, the children are the ones who will have to bear the brunt of the suffering. There appear to be no benefits for the children and young adults from the inoculations and only Costs!

The second issue is why the deaths shown on Fig. 2 were not predicted by the clinical trials. We examined the Pfizer trial results (based on a few months of testing) and did not see how (potentially) hundreds of thousands of deaths could have been predicted from the trials’ mortality results. Why this gap?

As we showed in the clinical trials section, 17.4 % of the Pfizer sample members were over 65, and 4.4 % were over 75. When the later phases of the trials started in late July 2020, the managers knew the COVID-19 age demographics affected from the July 2020 analog of Fig. 1. Rather than sampling from the age region most affected, they sampled mainly from the age region least affected! And even in the very limited sampling from the oldest groups, it is unclear whether they selected from those with the most serious comorbidities. Our impression is that the sickest were excluded from the trials, but were first in line for the inoculants.

It is becoming clear that the central ingredient of the injection, the recipe for the spike protein, will produce a product that can have three effects. Two of the three occur with the production of antibodies to the spike protein. These antibodies could allegedly offer protection against the virus (although with all the “breakthrough” cases reported, that is questionable), or could suppress serious symptoms to some extent. They could also cross-react with human tissue antigen, leading to potential autoimmune effects. The third occurs when the injected material enters the bloodstream and circulates widely, which is enabled by the highly vascular injection site and the use of the PEG-2000 coating.

This allows spike protein to be manufactured/expressed in endothelial cells at any location in the body, both activating platelets to cause clotting and causing vascular damage. It is difficult to believe this effect is unknown to the manufacturer, and in any case, has been demonstrated in myriad locations in the body using VAERS data. There appears to be modest benefit from the inoculations to the elderly population most at risk, no benefit to the younger population not at risk, and much potential for harm from the inoculations to both populations. It is unclear why this mass inoculation for all groups is being done, being allowed, and being promoted.

5. Overall conclusions

The people with myriad comorbidities in the age range where most deaths with COVID-19 occurred were in very poor health. Their deaths did not seem to increase all-cause mortality as shown in several studies. If they hadn’t died with COVID-19, they probably would have died from the flu or many of the other comorbidities they had. We can’t say for sure that many/most died from COVID-19 because of: 1) how the PCR tests were manipulated to give copious false positives and 2) how deaths were arbitrarily attributed to COVID-19 in the presence of myriad comorbidities.

The graphs presented in this paper indicate that the frail injection recipients receive minimal benefit from the inoculation. Their basic problem is a dysfunctional immune system, resulting in part or in whole from a lifetime of toxic exposures and toxic behaviors. They are susceptible to either the wild virus triggering the dysfunctional immune system into over-reacting or under-reacting, leading to poor outcomes or the injection doing the same.

This can be illustrated by the following analogy. A person stands in a bare metal enclosure. What happens when the person lights a match and drops it on the floor depends on what is on the floor. If the floor remains bare metal, the match burns for a few seconds until extinguished. If there is a sheet of paper on the floor under the match, the match and the paper will burn for a short time until both are extinguished. If, however, the floor is covered with ammonium nitrate and similar combustible/explosive materials, a major explosion will result! For COVID-19, the wild virus is the match. The combustible materials are the toxic exposures and toxic behaviors. If there are no biomarker ‘footprints’ from toxic exposures and toxic behaviors, nothing happens. If there are significant biomarker ‘footprints’ from toxic exposures and toxic behaviors, bad outcomes result.

Adequate safety testing of the COVID-19 inoculations would have provided a distribution of the outcomes to be expected from ‘lighting the match’. Since adequate testing was not performed, we have no idea how many combustible materials are on the floor, and what the expected outcomes will be from ‘lighting the match’.

The injection goes two steps further than the wild virus because 1) it contains the instructions for making the spike protein, which several experiments are showing can cause vascular and other forms of damage, and 2) it bypasses many front-line defenses of the innate immune system to enter the bloodstream directly in part. Unlike the virus example, the injection ensures there will always be some combustible materials on the floor, even if there are no other toxic exposures or behaviors. In other words, the spike protein and the surrounding LNP are toxins with the potential to cause myriad short-, mid-, and long-term adverse health effects even in the absence of other contributing factors! Where and when these effects occur will depend on the biodistribution of the injected material. Pfizer’s own biodistribution studies have shown the injected material can be found in myriad critical organs throughout the body, leading to the possibility of multi-organ failure. And these studies were from a single injection. Multiple injections and booster shots may have cumulative effects on organ distributions of inoculant!

The COVID-19 reported deaths are people who died with COVID-19, not necessarily from COVID-19. Likewise, the VAERS deaths are people who have died following inoculation, not necessarily from inoculation.

As stated before, CDC showed that 94 % of the reported deaths had multiple comorbidities, thereby reducing the CDC’s numbers attributed strictly to COVID-19 to about 35,000 for all age groups. Given the number of high false positives from the high amplification cycle PCR tests, and the willingness of healthcare professionals to attribute death to COVID-19 in the absence of tests or sometimes even with negative PCR tests, this 35,000 number is probably highly inflated as well.

On the latter issue, both Virginia Stoner [85] and Jessica Rose [86] have shown independently that the deaths following inoculation are not coincidental and are strongly related to inoculation through strong clustering around the time of injection. Our independent analyses of the VAERS database reported in Appendix 1 confirmed these clustering findings.

Additionally, VAERS historically has under-reported adverse events by about two orders-of-magnitude, so COVID-19 inoculation deaths in the short-term could be in the hundreds of thousands for the USA for the period mid-December 2020 to the end of May 2021, potentially swamping the real COVID-19 deaths. Finally, the VAERS deaths reported so far are for the very short term. We have no idea what the death numbers will be in the intermediate and long-term; the clinical trials did not test for those.

The clinical trials used a non-representative younger and healthier sample to get EUA for the injection. Following EUA, the mass inoculations were administered to the very sick (and first responders) initially, and many died quite rapidly. However, because the elderly who died following COVID-19 inoculation were very frail with multiple comorbidities, their deaths could easily be attributed to causes other than the injection (as should have been the case for COVID-19 deaths as well).

Now the objective is the inoculation of the total USA population. Since many of these potential serious adverse effects have built-in lag times of at least six months or more, we won’t know what they are until most of the population has been inoculated, and corrective action may be too late.

All the authors contributed equally and approved the final version of the manuscript.

Author’s contribution

Kostoff RN contributed to this paper with conception, data analysis, and writing the manuscript; Calina D contributed to data analysis, writing the manuscript, and editing; Kanduc D participated in data analysis and writing the manuscript; Briggs MB participated in data analysis, results validation, and graphics development; Vlachoyiannopoulos P participated in writing the manuscript; Svistunov AA participated in editing and reviewing the manuscript; Tsatsakis A participated in editing and reviewing the manuscript; all the authors contributed equally and approved the final version of the manuscript.

Ethical approval

Not applicable.

Declaration of Competing Interest

The authors declare that they have no competing interests. Aristides Tsatsakis is the Editor-in-Chief for the journal but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article.

Acknowledgement

Not applicable.

Appendix A

EXPECTED DEATHS IN 65+ DEMOGRAPHIC VS COVID-19 INOCULATION DEATHS

The goal of this appendix is to estimate the number of actual deaths from the COVID-19 inoculation based on the number of deaths following inoculation reported in VAERS [93,94,101]. The approach used will: 1) identify the number of deaths following COVID-19 inoculation that would have been expected without COVID-19 inoculation (i.e., pre-COVID-19 death statistics);2)

relate the VAERS expected death data to the actual number of deaths expected based on historical death statistics; and3) apply this ratio to scale-up the deaths attributed to COVID-19 inoculation reported in VAERS to arrive at actual deaths attributable to COVID-19 inoculation.

For example, if ten deaths could be shown in VAERS to reflect expected pre-COVID-19 deaths, and the actual number of expected pre-COVID-19 deaths from historical data was 100, the scaling factor of deaths would be ten to translate VAERS-reported deaths to actual deaths. Then, the deaths reported in VAERS that can be attributed to the COVID-19 inoculation will be multiplied by the expected deaths scaling factor, ten, to arrive at the actual number of deaths resulting from the COVID-19 inoculation. Thus, if VAERS shows fifty deaths that can be attributed to the COVID-19 inoculation, then the actual number of deaths attributed to COVID-19 will be 500 with these assumptions [3].

The basis for our approach is the following statement from the USA Federal government: “Healthcare providers are required to report to VAERS the following adverse events after COVID-19 vaccination [33] and other adverse events if later revised by FDA” [96,102,103]. “Serious AEs regardless of causality.”, including death [3,95].

If there had been full compliance with this requirement in VAERS, then the VAERS-reported deaths would have equaled the sum of1)

actual expected deaths (based on past statistics)2)

actual deaths over and above expected deaths that could be attributed to the COVID-19 inoculations.

Based on this requirement, we will generate a rough estimate (in the simplest form possible) of the number of deaths that would have occurred in the 65+ demographic if there had been no COVID-19 “pandemic”. Then, we will relate this number to the number of deaths reported to VAERS following COVID-19 inoculations in the 65+demographic. This would provide a “floor” for estimating the fraction of actual deaths reported to VAERS. This will be followed by parameterizing potential deaths attributable to the COVID-19 inoculations and displaying the effects on ratio of reported deaths to actual deaths. We will perform a global analysis and a local analysis, to see whether major or minor differences occur. The local analysis (Section A1-a2) may be somewhat easier to comprehend than the global analysis, but both come to similar conclusions.

A1-a Deaths Following COVID-19 Inoculations Reported to VAERS Compared to Expected Deaths

A1-a . Problems with VAERS

Before we discuss numbers of adverse events reported by VAERS, we need to identify potential shortcomings of, and problems with, VAERS, so these numbers of adverse events can be understood in their proper context. As stated previously, VAERS is a passive surveillance system managed jointly by the CDC and FDA, and historically has been shown to report about 1% of actual vaccine/inoculation adverse events (confirmed by the first principles analysis that follows in this appendix). There is no evidence that even the 1% reported have been selected randomly.

Some of this gross underreporting of adverse events reflects a major conflict-of-interest of CDC with respect to VAERS. CDC provides funding for administration of many vaccines, including the COVID-19 inoculations. Prior to COVID-19, the CDC provided about five billion dollars annually to the Vaccines for Children Program alone [102].

For COVID-19, the CDC has received many billions of dollars in supplemental funding for myriad activities, including vaccine distribution. It is difficult to separate out the CDC funding available for vaccine distribution from other CDC COVID-19 related activities, but one budget item (of many) should illustrate the magnitude of the effort: “Coronavirus Response and Relief Supplemental Appropriations Act, 2021 (P.L. 116–260): P.L. 116–260 provided $8.75 billion to CDC to plan, prepare for, promote, distribute, administer, monitor, and track coronavirus vaccines to ensure broad-based distribution, access, and vaccine coverage.” [3]. Low reporting rates of actual adverse events in VAERS should not be surprising, since the same organization that receives multi-billions of dollars in funding annually for promoting and administering vaccines also has responsibility for monitoring the safety of these products (whose liability has been waived).

In addition, the 1% reporting rates came from a thirty-day tracking study [22], and therefore are strictly applicable to very near-term adverse events. For mid-term and especially long-term events, the reporting rates would be much lower, since the links between inoculation and adverse events would be less obvious. That doesn’t mean these non-very-short-term adverse events don’t exist; it just means they haven’t been tracked. Absence of evidence is not evidence of absence. Thus, the VAERS numbers should be viewed as a very low “floor’ of the numbers and types of adverse events from COVID-19 inoculations that exist in the real-world.

A1-a2 Global analysis

We used 2019 death statistics from CDC to start the analysis. According to search results from CDC Wonder [104] obtained 11 June 2021, there were 2,117,332 deaths from all causes for people aged 65+ in the United States in 2019. Assuming uniformity throughout the year, there would have been ˜882,000 deaths occurring the first five months of the year, and that number will be used as the expected deaths for the first five months of 2021. From the same source, the population estimate is ˜54,000,000 for the 65+ age range. From CDC COVID-19 data tracker, the number of people 65+ vaccinated with at least one dose is ˜44,000,000 [24]

For those who were inoculated somewhere in the time frame 1 January 2021 to 31 May 2021, the number who would have been expected to die in the period from inoculation to 31 May will be a function of the duration of this period. For example, if all 44,000,000 people had been fully inoculated on 1 January 2021, then the number expected to die post-inoculation from non-COVID-19 inoculation causes would be simply (44,000,000/54,000,000) x 882,000, or ˜723,000 deaths. Conversely, if all 44,000,000 people had been fully inoculated on 31 May 2021, then the number expected to die post-inoculation from non-COVID-19 inoculation causes would be extremely small [24].

For an accurate estimation of the number expected to die post-inoculation from non-COVID-19 causes, one would need to integrate the time between inoculation and 31 May over the inoculation temporal distribution function. For present purposes, we will do a very rough approximation by modeling the inoculation distribution function as a delta function occurring at a mean temporal location. In other words, we compress all inoculations an individual receives into one, identify the mean temporal location from the actual inoculation distribution function, and compute the expected deaths based on the distance from 31 May to the temporal mean point.

From a graph of inoculation trends in the CDC data tracker [101] the distribution appears to be non-symmetrical pyramidal, rising to a peak in mid-April. This is slightly over the 2/3 point in the five-month range of interest. We will approximate the mean time point as 2/3 of the distance.

Table A1 displays the mean time normalized to the five-month study window vs potential deaths from COVID-19 inoculation (not expected from prior census data) normalized to the deaths expected from prior census data. Each cell represents the percent of deaths reported in VAERS following inoculation relative to total deaths (number of deaths expected from prior census data plus number of deaths following COVID-19 inoculation not contained in the expected death group). The model on which the table is based is as follows: there are two classes of deaths for the period following COVID-19 inoculation. One is the deaths expected from prior census data, and the other is deaths attributable mainly to COVID-19 inoculation. There would be potentially substantial overlap between the two in this age group (and perhaps other age groups as well). We assume that we can tag those individuals who would be expected to die based on prior census data. The remaining deaths attributable to COVID-19 inoculation not contained within the tagged group are classified as potential COVID deaths in Table A1.

Table A1. Expected deaths from non-COVID-19 causes for inoculees (Thousands).

Potential covid deaths/#
non-covid expected
Mean time location/five months
0%REP1/3%REP1/2%REP2/3%REP1%REP
07230.54820.743620.982421.474.7775
.510850.337230.55430.663630.987.1450
114460.259640.377240.494840.749.5137

Consider the cell (2/3,0). The mean time is about mid-April 2021 and the only deaths occurring are those expected (some may have died because of the inoculation, but they were sufficiently ill that they would have died during that period without the inoculation). There were 723,000 expected deaths and ˜3560 reported, yielding a ratio of deaths reported in VAERS to actual deaths of ½%.

Consider the cell (1/2,1). The mean time would have been about mid-March 2021 and the inoculation distribution would have resembled an isosceles triangle. The total deaths occurring are those expected and an equal number whose deaths were attributed to COVID-19 inoculation but did not overlap with those in the tagged expected group (there still could have been some/many in the latter group that may have died because of the inoculation, but they were sufficiently ill that they would have died during that period without the inoculation). There were 724,000 total deaths that occurred during that period and ˜3560 reported, yielding a ratio of deaths reported in VAERS to actual deaths of ½%. [3]

So, according to Table A1, focusing on the parameter most closely reflecting the actual inoculation distribution (2/3), the reporting percentages of actual to total are about 1%. This mirrors the Harvard Pilgrim study results (referenced in our vaccine safety study) which were obtained through an entirely different empirical approach [4]. At least for deaths reporting, there appears to be an approximately two order of magnitude difference between actual and reported deaths in VAERS.

Table A1 used two parameters to examine a broad spectrum of possible results, the mean time and the number of deaths solely attributable to COVID-19 inoculation. The mean time parameter was fairly well known and constrained in interpretation, because it was based on an empirical inoculation distribution function. The number of deaths solely attributable to COVID-19 inoculation is completely unknown.

As will be shown in the next section, the numbers of deaths reported in VAERS are strongly related to the inoculation date by clustering, but those who died might also have been those who would have died anyway because they were expected to die. There were probably some of each in that group reported. But we have no idea of the total number whose death could be directly attributed to COVID-19 inoculation and who were not in the group expected to die. For all we know, there could have been ten million people in that group, and only an extremely small fraction of that total group was reported in VAERS.

Suppose, for example, that the actual number of deaths reported in VAERS came from two groups: 90 % were from the inoculation-attributable death group and 10 % were from the expected death group. Assume there is no overlap between the two groups. In that case, what VAERS shows is not that 1% of actual expected deaths were reported, but rather that 1/10 of one percent of the expected deaths were reported. If that metric is used as the standard to scale up to total deaths, then the number in the actual inoculation-attributable death group is not 100 times the VAERS reported deaths, but rather 1000 times the VAERS-reported deaths! The point is we can’t “reverse-engineer” the reported VAERS death numbers to get the actual inoculation-attributable deaths because it depends on the unknown contribution of each of the two groups (expected deaths and inoculation-attributable deaths) to the VAERS reported deaths, and we can’t separate those out.

All this analysis shows is that, at best, only about 1% of the number expected to die was reported, and because the number reported in VAERS included deaths from both groups, the fraction from each actual group of deaths could not be determined. Realistically, we may have to wait until mid-2022, when the 2021 total deaths for each age group are finalized, to ascertain whether we can see increases in all-cause mortality that could have come from the inoculation-attributable deaths.

A1-a3 Local Analysis

Another way of estimating VAERS reporting efficiency is to perform a local analysis, focused on clustering about date of COVID-19 inoculation. For the 65+demographic, the post-inoculation deaths cluster near the vaccination date, providing evidence of a strong link to the inoculation.

Following the approach in the first section of this appendix, we calculate the deaths expected in any ten-day period based on 2019 pre-COVID-19 death statistics. For the inoculated group, the number of deaths expected for any ten-day period are (2,117, 332 deaths/per year) x (44,000,000/54,000,000 fraction of population in age range inoculated) x (10/365 fraction of year), or ˜47,270 deaths.

˜BEST-CASE SCENARIO
Consider the ten days following inoculation (including day of inoculation). Approximately 2,000 deaths were reported in VAERS. Assume hypothetically that all these deaths were in the expected category; this can be viewed as a best-case scenario. In this ˜best-case scenario, where the concentration of deaths is the highest and is normalized to the expected number of non-COVID-19 inoculation deaths (excluding deaths due solely to COVID-19 inoculation), 2,000/47,270 % of actual deaths (inoculation-related or not), or 4.23%, are reported in VAERS. Thus, at best, VAERS is underreporting by a factor of ˜20.

Suppose in that ten-day interval there had been 10,000 deaths that could be directly attributed to COVID-19 inoculation in addition to the expected deaths. This would have given a ratio of 2,000/57,270 actual total deaths, or 3.5 % reported in VAERS. This latter approach requires less assumptions than the former approach, but still yields results of only a few percent actual deaths reported in VAERS.

The Harvard Pilgrim electronic tracking study of post-vaccination events reported to VAERS performed in 2010 [4] showed a 1 % reporting rate for a thirty-day period. In the present case, ˜2900 post-inoculation deaths were reported to VAERS within thirty days of inoculation, or ˜82 % of total deaths for the 65+demographic. Substituting thirty days for ten in the above computation yields 141,810 expected non-COVID-19 post-inoculation deaths for the thirty-day period, or 2% that are reported in VAERS. The Harvard study used an electronic system that automatically tracked every event that occurred, no matter how small. Because of the effort (time and cost) required to submit event reports to VAERS, we suspect that only the more serious events, such as death, would be reported, and even in this case, the numbers reported are miniscule.

We also did an analysis for sixty days post-inoculation. In the present case, ˜3300 post-inoculation deaths were reported to VAERS within sixty days of inoculation, or ˜93 % of total deaths for the 65+demographic. Substituting sixty days for ten in the above computation yields 283620 expected non-COVID-19 post-inoculation deaths for the thirty-day period, or 1.2 % that are reported in VAERS. Remember, this normalization is based only on expected deaths. If 100,000 deaths attributable mainly to the COVID-19 inoculation beyond those that overlapped with the expected group occurred during this period, then the denominator would have to be increased by 100,000, yielding a VAERS reporting rate of 0.86 %.

Thus, both the global and local analyses, and the Harvard Pilgrim empirical analysis, are converging on the same two orders-of-magnitude difference between the actual number of deaths that occurred in the USA and those reported in VAERS. Depending on how many people have really died as a result of the COVID-19 inoculation, this reporting rate could well be a fraction of a percent!

A1-a3a Local Clustering Analysis

We end this appendix with one more example from the local analysis. Some background perspective is required. In the buildup to the pandemic (putting aside the issue of high false positives from PCR tests run at high numbers of amplification cycles), almost anyone who died with COVID-19 was assumed to have died from COVID-19, irrespective of the number of potentially lethal comorbidities they had. The CDC admitted later that about 94 % of the deaths attributed to COVID-19 would ordinarily have been attributed to one of the comorbidities.

For this example, we adopt a similar philosophy for the COVID-19 inoculations. People in the 65+ demographic who have died following inoculation are divided into two groups: those who died from the inoculation and those who died as expected based on pre-COVID-19 death data. The two groups range from being entirely separate to completely overlapping. We will examine two cases: entirely separate and completely overlapping.

How are the members of each group determined? The death from inoculation group consists of those whose deaths cluster significantly around the date of inoculation. The deaths expected group are the number who would have died in the absence of COVID-19. We allow for overlap, where each person who died can be double-valued (a member of both groups), but not double-counted.

To obtain a relatively precise estimate of expected deaths, we would want to select a region of time where the distribution function has substantially leveled off. From Fig. A1, the thirty-sixty-day range appears reasonable. However, there is a time issue here. Given the lag time in data reported by VAERS, most of the data in this range will probably have come from inoculations in January and February, and early-mid March, approximately 35 percent of the total inoculations. Therefore, we could multiply the thirty-sixty-day average number of deaths by ˜3 to obtain ˜40 expected deaths per day. An even simpler way to estimate the expected deaths reported in VAERS is to use the 15−30-day average shown, which will represent most of the range. This value is ˜37, which is close to the ˜40 obtained with the above approximation. This analysis should be re-run in three-four months, when more of the long-range data has been filled in.

Fig. A1

Table A2 shows the results of our analysis. As stated previously, two separate cases were analyzed: completely separate groups and completely overlapping groups. Two values of daily expected deaths were used: the 37 as described above, and 20 to account for potentially lower expected death reporting when the VAERS data has filled in more completely.

Thus, based on the deaths reported in VAERS following COVID-19 inoculation, and assuming the inoculation-related deaths are reported in the same ratio as expected deaths, the actual number of deaths strongly related to the COVID-19 inoculation should be scaled up by factors of 100−200. For the broadest definition of VAERS coverage provided by CDC Wonder, which includes the USA and all territories, protectorates, and possessions, the total deaths following COVID-19 were ˜5200 in early June 2021. Using our scaling factors, this translates into somewhere between one-half million and one-million deaths, and this has not taken into account the lag times associated with entering data into VAERS. Compared with the ˜28,000 deaths the CDC stated were due to COVID-19 and not associated morbidities for the 65+ age range, the inoculation-based deaths are an order-of-magnitude greater than the COVID-19 deaths! It should be remembered these are only the very-short-term inoculation-based deaths, and could increase dramatically if mid- and long-term adverse effects come to fruition.

We end this appendix with an even more unsettling possibility. The main assumption upon which the results in Table A2 were based is that the post-inoculation temporal distribution function shown in Fig. A1 could be divided into two regions. The strongly varying region originating from the inoculation date reflected deaths from the inoculation, and the essentially flat region that followed reflected expected deaths (that flat region also started at the inoculation date, and formed the base on which the highly varying region is positioned). This model excludes the possibility that deaths from the inoculation extend well beyond the limits of the highly varying region.

Table A2. Actual COVID-19 inoculation-based deaths.

Actual COVID-19 inoculation-based deaths from vaers reporting
Separate GroupsOverlapping Groups
Expected Deaths Reported37203720
Range Of Days Inoculation Deaths0−300−300−300−30
Total Reported Deaths Over Range2901290129012901
Total Expected Deaths Over Range11476201147620
Inoculation-Based Deaths Reported1754228129012901
Expected Deaths Reported/Total Expected.0077.0041.0077.0041
Total Actual Inoculation-Based Deaths Using Expected Ratio (Above)227792556341376753707561

We know in general this is not true. There can be lag effects such as ADE in the Fall viral season, and longer-term effects such as autoimmune diseases. We postulate that there are other effects from the inoculation that could result in the same flat death profile as that for expected deaths.

Consider the following. Some of the damage we have seen following the inoculations in VAERS includes coagulation/clotting effects and neurological effects of all types [63]. If these effects are not lethal initially, they raise the level of dysfunction. Thus, platelet aggregation has increased to a new base level, and micro-clots have raised the probability of serious clots forming from other lifestyle factors [105]. Death of specific neurons can increase the risk of Alzheimer’s disease or Parkinson’s disease, and can accelerate the onset of these and many other diseases. Thus, the adverse impacts of the COVID-19 inoculations could be viewed as raising the level of expected deaths in the future. Any deaths of this nature reported in VAERS would need to be viewed as inoculation-driven, and the expected deaths used in the computations would be reduced accordingly.

Consider Table A3 below. The “expected deaths reported” have been reduced below their counterparts in Table A2 to illustrate parametrically how the total inoculation-based deaths would change from VAERS reporting if this baseline effect is operable. While Table A2 used values of 37 and 20 for expected deaths, Table A3 uses values of 10 and 15.

Table A3. Possible COVID-19 inoculation-based deaths.

Possible COVID-19 inoculation-based deaths from vaers reporting
Separate GroupsOverlapping Groups
Expected Deaths Reported10151015
Range Of Days Inoculation Deaths0−300−300−300−30
Total Reported Deaths Over Range2901290129012901
Total Expected Deaths Over Range310465310465
Inoculation-Based Deaths Reported2591243629012901
Expected Deaths Reported/Total Expected.0021.0031.0021.0031
Total Actual Inoculation-Based Deaths Using Expected Ratio (Above)12338107858061381429935806

Thus, if the baseline of the host for coagulation/clotting, inflammation, hypoxia, neurodegeneration, etc., has been raised by the inoculations, translating into an increase in expected deaths and accelerated deaths, then it is entirely plausible that the VAERS death numbers reflect over a million deaths from COVID-19 inoculations so far. These are very short-term-effects only, and time will tell whether the large potential waves of ADE-driven deaths and autoimmune-driven deaths come to pass.

Appendix B

DETAILED ANALYSIS OF MAJOR COVID-19 INOCULANT CLINICAL TRIALS

A2-a Clinical Trials in the Mainly Adult Population

Definitions

Efficacy is the degree to which a vaccine prevents disease, and possibly also transmission, under ideal and controlled circumstances – comparing a vaccinated group with a placebo group [106].

Effectiveness refers to how well a vaccine performs in the real world [107]

Relative Risk (RR) is computed by dividing the percentage of patients that contracted disease in the vaccine arm by the percentage of patients that contracted disease in the placebo arm.

Relative Risk Reduction (RRR) is computed by subtracting the RR from 1.

Absolute Risk Reduction (ARR) is computed by subtracting the percentage that contracted disease in the vaccine arm from the percentage that contracted disease in the placebo arm.

Absolute Risk = probability = incidence.

Cumulative Incidence represents the number of new cases in a period of time / population at risk.

Incidence Density is the number of new cases of a given disease during a given period in specified population; also, the rate at which new events occur in a defined population.

Immunogenicity is the ability of a molecule or substance to provoke an immune response or the strength or magnitude of an immune response. It can be a positive (wanted) or negative (unwanted) effect, depending on the context.

Immune Response is an integrated systemic response to an antigen (Ag), especially one mediated by lymphocytes and involving recognition of Ags by specific antibodies (Abs) or previously sensitized lymphocytes [108]

Safety data for Pfizer and Moderna trials:

There were two major COVID-19 inoculant clinical trials: Pfizer/BioNTech and Moderna.

The Pfizer clinical trials were titled officially “a phase 1/2/3, placebo-controlled, randomized, observer-blind, dose-finding study to evaluate the safety, tolerability, immunogenicity, and efficacy of sars-cov-2 rna vaccine candidates against covid-19 in healthy individuals” [98]. The “Actual Study Start Date” was 29 April 2020, the “Estimated Primary Completion Date” was 2 November 2020, and the “Estimated Study Completion Date” is 2 May 2023. Thus, the mass inoculation rollout so far has been conducted in parallel with the Pfizer Phase III Clinical Trial. For all practical purposes, the mass global inoculation of the Pfizer inoculant recipients can be considered Phase III 2.0 of the Clinical Trials! The inclusion criteria for the official Phase III Clinical Trials incorporated (as stated in the title and in the protocol document) healthy individuals, while the criteria for mass inoculation went well beyond healthy individuals. In essence, we have an official Phase III Clinical Trial with ˜43,000+ healthy individuals, and an unofficial Phase III Clinical Trial with billions of individuals covering a wide spectrum of health levels [98].

The Pfizer Phase III trials were initiated July 2020, the efficacy data were submitted to the FDA for EUA approval in November 2020, and FDA approval was granted in December 2020. Six deaths occurred in the Pfizer trial, two in the inoculated group and four in the placebo group (which received saline) [33]. The two inoculated, both over the age of 55, died of cardiovascular causes. One died three days after inoculation and the other died 62 days after inoculation [109]. These two deaths were comparable (in frequency and cause) to placebo group deaths and perhaps more importantly, similar to the general population at that age. In the case of Moderna, there were 13 deaths, six in the inoculated group, seven in the placebo group (normal saline placebo, a mixture of sodium chloride in water 0.90 % w/v) at 21–57 days after the inoculation ([103]b).

In a report by the Norwegian National Medicines Association, published on 15 January 2021, there were 23 elderly people (all over the age of 75 and frail) in nursing homes, who died at various intervals from the time of inoculation with mRNA inoculant The report then suggested that, following the assessment, 13 of the 23 deaths would have been a direct result of the side effects of inoculation. It is possible that the other 10 deaths were post-inoculation, but not directly related to side effects, so not necessarily related to the inoculant itself [109].

It is no surprise that frail elderly people can be fatally destabilized by adverse reactions associated with post-inoculation inflammation, which in a young adult would have been considered minor. It is also no surprise that frail elderly people with comorbidities can be fatally destabilized from COVID-19 infection, which in a young adult or child would have been considered minor. A frail elderly person can be fatally destabilized by a simple coughing fit! This does not mean that these deaths are not events that need to be taken very seriously; on the contrary, if confirmed, they should guide inoculation policies in this category of patients from now on. Specifically, each case should be carefully assessed and an inoculation decision made based on the risk-benefit ratio [110].

In light of these data, the question may arise as to why there were no inoculant-attributed deaths in clinical testing of inoculants. The answer is that neither Pfizer nor Moderna included frail patients and included only a small number of very elderly patients – those over 75 accounted for 4.4 % of the total tested for Pfizer and 4.1 % for Moderna. While they could not in fact determine a causal relationship between inoculation and death, they also could not rule out that the inoculations had accelerated the deterioration of the condition of those patients [33].

Effectiveness data

As defined previously, the effectiveness of a vaccine lies in its ability to prevent a particular disease. If designed, tested, and administered correctly, authorized vaccines are effective in preventing disease and protecting the population. Like medicines, vaccines are not 100 % effective in all vaccinated people. Their effectiveness in a person depends on several factors. These include: age; other possible diseases or conditions; time elapsed since vaccination; previous contact with the disease.

To be declared safe and effective, a vaccine against COVID-19 infection must pass a series of tests and must meet regulatory standards, like any other vaccine or drug approved on the pharmaceutical market [111].

Regarding Pfizer and Moderna trials: The first important note is that maximum efficiency does not come immediately, because the immune response needs time.

In the case of Pfizer, the chance of developing COVID-19 becoming virtually the same between the inoculated and placebo groups increases up to 12 days after the first inoculation, then gradually decreases for those inoculated. The inoculum efficiency between the first and second doses is 52 % [106], but it is unclear what long-term protection a single dose provides. After the second dose, the effectiveness rises to 91 % and only beyond 7 days after the second dose is 95 % reached. However, the ARR for the latter case is only 0.7 % [112]. In other words, within 12 days after the first dose we can get COVID-19 as if we had not been inoculated. Another important aspect is that we still do not know if the Pfizer inoculant prevents severe cases. Seven days after the second dose, there were four severe cases of COVID-19, one in the inoculated group and three in the placebo group, which is far too low for us to make a statistical assessment. There are as yet no data on the inoculant’s ability to prevent community transmission. Realistically, the effectiveness of the inoculant in preventing asymptomatic cases has not been tested.

For Moderna, the effectiveness is only 50 % in the first 14 days after the first dose and reaches a maximum of 92.1 % on the edge of the second dose (ARR of 1.1 %, which is 28 days, not 21 as in the case of Pfizer) [46]. Moderna also did not test the long-term efficacy of a single dose. Then, 14 days after the second dose, the effectiveness rises to 94.1 %, with the amendment being an average. Thus, in people over 65 it was 86.4 %, compared to 95.6 % in the 18–65 age range ([103]). It is a minor difference from Pfizer, which declares equal efficiency in all age groups. An important observation is the statement by Moderna that their inoculant prevents severe cases, but only more than 14 days after both doses [126]. All 30 severe cases were in the placebo group, suggesting 100 % efficacy. After a single dose, there were two severe cases among those inoculated and four in the placebo group [33]. Last, but not least, unlike Pfizer, Moderna tested the presence of asymptomatic infection by RT-PCR before the second dose: there were 39 asymptomatic cases in the placebo group and 15 in the inoculated group. It is difficult to draw definitive conclusions due to the small number of cases. These data suggest that the inoculant reduces, but does not prevent, asymptomatic transmission [126].

A2-b Ongoing Clinical Trials in the Pediatric Population

In a recent Phase III study performed in the pediatric population, Comirnaty (Pfizer) was tested on a group of 2,260 children, aged 12–15, years who had no previous clinical signs of SARS-CoV-2 infection. They were divided into two groups, one placebo (978 children) and the other with Comirnaty (1005 children). In the Comirnaty group, of the 1005 children in whom the serum was administered, none developed COVID-19 disease, compared with the placebo group in which 16 children in 978 had clinical signs of the disease. The Pfizer study showed that the children’s immune response was comparable to the immune response in the 16–25 age group (measured by the level of antibodies against SARS-CoV-2). It could be concluded that in this study, Comirnaty was 100 % effective in preventing SARS-CoV-2 infection, although the actual rate could be between 75 % and 100 %. [63]. The results will be evaluated by the FDA and EMA.

The predictive value (for mass inoculation results) of the Comirnaty trial for the children aged 12–15 years is questionable. There were 1005 children who were inoculated with Comirnaty. Using the rule of three in statistics, where to obtain a predictive result of 1/x with high confidence (e.g., 1 in a thousand), 3x participants are required for the test sample. For the Comirnaty test sample of 1005, an adverse event of about 1/340 could be detected with high confidence.

What does this mean in the real world? In the USA, there are approximately 4,000,000 children in each age year for adolescents. Thus, there are ˜16,000,000 children in the 12–15 age band. A serious adverse event, including death, that occurred at a 1/800 rate would not be detectable with high confidence in a sample of 1005 people. Thus, the results of the trials for 1005 children would allow for 20,000 children to suffer a non-trial-detected serious adverse event, including death, when extrapolated to potential inoculation of all children in the 12–15 age group! Given that the risk of contracting COVID-19 with serious outcomes is negligible in this population, proceeding with mass inoculation of children 12–15 years old based on the trials that were conducted cannot be justified on any cost-benefit ratio findings.

Also, the evaluation of efficacy in children aged 6 months to 11 years has recently begun and continues [24]. Pfizer began enrolling children under 12 to evaluate the COVID-19 mRNA inoculant. Also, Comirnaty will be evaluated in a new clinical trial for children aged 6 months to 11 years. In the first phase, the study will enroll 144 people and will identify the required dose for 3 age groups (6 months – 2 years, 2–5 years and 5–11 years). After a 6-month follow-up period, the parents/guardians of children in the placebo group will have the option of allowing their children to receive the inoculation. The results are expected in the second half of 2021.

Moderna also began a study to evaluate the mRNA inoculation in children aged 6 months to 12 years. Both companies have already started testing vaccines in 14-year-olds. In the US, children make up 23 % of the population [113].

Data on the risks and benefits of possible inoculation in children and adolescents are currently insufficient and no recommendation can be made. Specifically, mass child inoculations cannot be recommended until the benefits and minimal projected risks have been demonstrated in a sufficiently large trial to provide confidence that mass inoculation will have an acceptable level of adverse effects relative to the demonstrated benefits. On the other hand, children often experience COVID-19 asymptomatically, and the SARS-CoV-2 infection progresses harmlessly. Currently, in the context of limited inoculation capacities, there is no indication of urgent inoculation of children. In the context of declining incidences of SARS-CoV-2 infections and demonstrated low serious adverse effects from COVID-19 infections for children and adolescents, the issue of inoculating children and adolescents is no longer paramount. Authorized forums must calculate what prevails for children and adolescents: the benefits or risks.

A2-c Clinical Trial Issues for Other Categories

Although people with severe comorbidities such as obesity or oncological conditions were not initially included in the clinical trials that led to obtaining EUA, they were included in subsequent studies, some even ongoing. In their case, it seems that the efficacy was lower compared to the results obtained initially with healthy adults.

The interim analysis of data from a prospective observational study indicates the need to prioritize cancer patients for timely (respectively 21-day) booster administration in the case of administration against COVID-19 with Comirnaty. According to the study, the effectiveness of a single dose of Comirnaty among cancer patients is low, but the immunogenicity of patients with solid cancers increased at 2 weeks after receiving the second dose of inoculant 21 days after the first dose. Because the study was conducted in the UK, participants inoculated before December 29, 2020 received two doses of Comirnaty 21 days apart, and those who started the regimen after this date were scheduled to receive a second dose of Comirnaty 12 weeks apart. first administration. Thus, the study continues to collect data from participants receiving Comirnaty 12 weeks after the first dose.

Approximately 21 days after a single dose of Comirnaty, the proportion of study participants who tested positive for anti-S IgG antibodies was [114]:

94 % among healthy participants;

38 % among patients with solid cancers;

18 % among patients with hematological cancers.

Among participants who received the 21-day booster and for whom biological samples were available two weeks after the second dose, the following proportions of confirmation as seropositive for anti-S IgG antibodies were reported [114].

100 % of healthy participants, compared to 86 % of the same group of participants who did not receive the second dose;

95 % of patients with solid cancers, compared with 30 % of the same group of participants who did not receive the second dose;

60 % of patients with hematological cancers, compared with 11 % of the same group of participants who did not receive the second dose.

Two other studies suggest low immunogenicity in the context of Comirnaty administration in patients with hematological cancers. In one study, patients with chronic lymphocytic leukemia (CLL) had significantly reduced immune response rates to COVID-19 inoculation compared to healthy participants of the same age. Considerable variations in post-administration immune response have been reported among patients with CLL depending on their stage of treatment

The effectiveness of Comirnaty administration was also evaluated in elderly patients with multiple myeloma [115]. 21 days after administration of the first dose of Comirnaty inoculation (before receiving the second dose), 20.5 % of patients with multiple myeloma compared to 32.5 % of control participants had neutralizing antibodies against SARS-CoV-2. One possible explanation could be that the therapy negatively affects the production of antibodies. However, the administration of the second dose is important for the development of the immune response in these patients [115].

Preliminary data from the v-safe surveillance system, the v-safe pregnancy registry and the Vaccine Adverse Event Reporting System (VAERS) do not indicate obvious safety signals regarding pregnancy or the associated neonatal implications with mRNA injections against COVID-19 in the third trimester of pregnancy [3]. The study included 35,691 pregnant women [116]. Compared to non-pregnant women, pregnant women reported more frequent pain at the injection site as an adverse event associated with mRNA COVID-19 vaccination, and headache, myalgia, chills, and fever were reported less frequently. In the context where initial clinical trials of messenger RNA-based inoculants have not evaluated the efficacy and safety of innovative technology among pregnant women, these preliminary data from the third trimester only help to inform both pregnant women and health professionals in making the inoculation decision. However, continuous monitoring through large-scale longitudinal studies remains necessary to investigate the effects associated with maternal anti-COVID-19 inoculation on mothers, pregnancies, the neonatal period and childhood.

On the other hand, the inoculation landscape has become even more complex due to new circulating viral variants. Authorities recommend genomic surveillance and adaptation in order to be effective against new variants (different from the initial strain that was detected at the end of 2019). The efficacy data of Comirnaty against circulating viral variants are highlighted in a very recent study in Israel which showed that the protection offered by the Pfizer inoculant against variant B.1.351 (first identified in South Africa) is lower [112].

The results have not yet been submitted to the expertise of specialists. The study compared nearly 400 adults who were diagnosed with COVID-19 at least 14 days after receiving one or two doses of the inoculant to the same number of uninoculated people. It was found that B.1.351 represents approximately 1 % of the COVID-19 cases studied. But among patients who received two doses of inoculant, the prevalence rate of the variant was eight times higher than in those not inoculated – 5.4 % compared to 0.7 %. This suggests that Comirnaty is less effective against variant B.1.351, compared to the original variant and variant B.1.1.7. The limitation of the study comes from the small number of adult people studied, but it is an alarm signal for a closer study of these cases. In addition, it seems that at present, the prevalence of this variant is low. On the other hand, in early April, Pfizer announced that according to the results of the Phase III study in the adult population, Comirnaty also demonstrated 100 % efficacy in the prevention of Covid-19 disease caused by SARS-CoV-2 variant B.1.351 (9 cases of Covid-19 were recorded, all in the placebo group, and after sequencing it was found that 6 had been determined by B.1.351) [117].

Appendix C

MID- AND LONG-TERM ADVERSE EFFECTS FROM PRIOR VACCINES

A 2020 study emphasizing mid- and long-term adverse effects from prior vaccines [4] identified the following sixteen mid- and longer-term potential issues concerning vaccines. These include:

3.1. Antibody-Dependent Enhancement (where enhanced virus entry and replication in a number of cell types is enabled by antibodies);

-1a. Intrinsic Antibody-Dependent Enhancement (where non-neutralizing antibodies raised by natural infection with one virus may enhance infection with a different virus);

-1b. Immune Enhancement (enhancement of secondary infections via immune interactions);

-1c. Cross-Reactivity (an antibody raised against one specific antigen has a competing high affinity toward a different antigen.);

-1d. Cross-Infection Enhancement (infection enhancement of one virus by antibodies from another virus);

3. 2. Vaccine-Associated Virus Interference (where vaccinated individuals may be at increased risk for other respiratory viruses because they do not receive the non-specific immunity associated with natural infection);

3. Vaccine-Associated Imprinting Reduction (where vaccinations could also reduce the benefits of ‘imprinting’, a protection conferred upon children who experienced infection at an early age)

4. Non-Specific Vaccine Effects on Immune System (where previous infections can alter an individual’s susceptibility to unrelated diseases);

5. Impact of Infection Route on Immune System (where immune protection can be influenced by the route of exposure/delivery);

6. Impact of Combinations of Toxic Stimuli (where people are exposed over their lifetime to myriad toxic stimuli that may impact the influence of any vaccine);

7. Antigenic Distance Hypothesis (negative interference from prior season’s influenza vaccine (v1) on the current season’s vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ≈ v2) but large between v1 and the current epidemic (e) strain (v1 ≠ e).);

8. Bystander Activation (activation of T cells specific for an antigen X during an immune response against antigen Y);

9. Gut Microbiota (Impact of gut microbial composition on vaccine response);

10. Homologous Challenge Infection Enhancement (the strain of challenge virus used in the testing assay is very closely related to the seed virus strain used to produce the vaccine that a subject received);

11. Immune Evasion (evasion of host response to viral infection);

12. Immune Interference (interference from circulating antibody to the vaccine virus);

­12a. Original Antigenic Sin (propensity of the body’s immune system to preferentially utilize immunological memory based on a previous infection when a second slightly different version of that foreign entity (e.g. a virus or bacterium) is encountered.);

13. Prior Influenza Infection/Vaccination (effects of prior influenza infection/vaccination on severity of future disease symptoms);

14. Timing between Viral Exposures (elapsed time between viral exposures);

15. Vaccine-Associated Enhanced Respiratory Disease (where vaccination enhances respiratory disease); and

16. Chronic Immune Activation (continuous innate immune responses).

Most of these events are not predictable, and most, if not all, would be possible for the COVID-19 inoculant in the mid- and long-term for adults and children.

3.3. Mid- and Long-Term Serious Illnesses for Adults and Children from Past Vaccines

As stated in the aforementioned 2020 study on vaccine safety: “The biomedical literature is very sparse with studies on long-term vaccine effects, especially long-term adverse effects. Large numbers of people and long periods of time are required to identify such adverse events, and draw statistically-valid connections between vaccinations and disease. These efforts would be very resource-intensive, and there appears to be little motivation among the vaccine producers and regulators to make these resources available for such studies. Thus, the following examples reflect the extremely small tip of an extremely large iceberg of long-term adverse vaccine effects.” [4]

“The two main categories of diseases reported in the biomedical literature triggered by past vaccinations are “Autoimmune (e.g., Systemic Lupus Erythematosus, Psoriasis, Arthritis, Multiple Sclerosis, Hepatitis, UveitisPseudolymphoma, Guillain-Barre Syndrome, Thrombocytopenic Purpura, etc.) and Neurological (e.g., Central Demyelinating Diseases, Developmental Disability, Febrile seizuresNarcolepsyEncephalomyelitisAutonomic Dysfunction, etc.). Others include Diabetes, Gastrointestinal, Joint-related, Necrobiotic GranulomaNeutropeniaPulmonary Fibrosis, etc.”

“Vaccinations may also contribute to the mosaic of autoimmunity [118]. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritisinflammatory myopathies, multiple sclerosis, Guillain-Barre syndrome, and vasculitis”.

“Studies have demonstrated a latency period of years between HiB vaccination and diabetes mellitus, and between HBV vaccination and demyelinating events [118] latency periods can range from days to years for postinfection and postvaccination autoimmunity”.

“Most of the extra cases of IDDM appeared in statistically significant clusters that occurred in periods starting approximately 38 months after immunization and lasting approximately 6–8 months. Immunization with pediatric vaccines increased the risk of insulin diabetes in NOD mice.Exposure to HiB immunization is associated with an increased risk of IDDM.” [4]

Thus, even the sparse past vaccine studies that went beyond the short-term showed latency effects of serious diseases occurring three years or more post-vaccination.

Appendix D

COST-BENEFIT ANALYSIS OF COVID-19 INOCULATIONS

This appendix presents a non-traditional best-case scenario pseudo-cost-benefit analysis of the COVID-19 inoculations for the 65+ demographic in the USA. In this incarnation of a cost-benefit analysis, the costs are the number of deaths resulting from the inoculations, and the benefits are the lives saved by the inoculations. The time range used was from December 2019 to end-of-May 2021.

It is assumed, in this best-case scenario, that all the deaths truly attributable to COVID-19 only could have been eliminated by the inoculations given (about half the USA population has been inoculated at this time) [88,119]. It can be conceptualized as the vaccines having been available in Summer 2019, and subsequent administration having eliminated all the deaths experienced that were truly attributable to COVID-19. If the cost-benefit ratio is poor for this best-case scenario, it will be very poor for any real-world scenario [120].

We will use Fig. 1Fig. 2 as starting points to conduct a cost-benefit analysis of COVID-19 inoculations for the most vulnerable demographic, those 65 + . We start with the official government numbers for COVID-19 and post-inoculation deaths, and modify them to arrive at actual deaths resulting from COVID-19 and the inoculations. We compare the two numbers (appropriately normalized) to ascertain costs vs benefits .

As Fig. 1 shows, there are three age bands that comprise the 65+ demographic. We weight the COVID-19 deaths per capita in each band by the band’s population, and divide the sum of these three products by the total 65+ population to arrive at an average COVID-19 deaths per capita of 0.0087 for the total 65+ demographic.

Fig. 2 contains two normalizations. First, the deaths were normalized by total inoculations given, not by people inoculated or people who had completed the full series of inoculations. We will retain the normalization by total inoculations given, since it will provide the most conservative results (largest denominator) for estimation purposes. Second, the deaths were normalized/restricted to those occurring within seven days post-inoculation. This normalization was done to compare across age bands, where the inoculations started at very different points in time. For the present cost-benefit purpose, where we are concentrating on the 65+ band, we remove this latter normalization, and include all post-inoculation deaths. Removing this normalization increases deaths per inoculation by about 40 % to a value of 0.000032, and offers a more credible comparison to the numbers from Fig. 1.

Thus, based on the CDC’s official numbers, there are an average COVID-19 deaths per capita of 0.0087 and an average deaths per inoculation of 0.000032 for the 65+ demographic. The chances of a person 65+ dying from an inoculation relative to their chances of dying from COVID-19 are approximately 0.0037, or about 1/270, based on these official CDC figures.

However, as we have shown previously, three corrections to these numbers are required to convert them to real-world effects. First, as the Harvard Pilgrim study has shown and as our results in Appendix 1 confirm, VAERS is underreporting actual deaths by about two orders of magnitude. Applying this correction alone to the above 1/270 ratio changes the risk benefit to about 1/3., Second, as the CDC has stated, approximately 94 % of the COVID-19 deaths could have been attributed to any of the comorbidities these patients had, and only 6% of the deaths could actually be attributed to COVID-19. As we pointed out, if pre-clinical comorbidities had been included, this number of 6% would probably be decreased further. For conservative purposes, we will remain with the 6%. Applying this correction to the 1/3 risk-benefit ratio changes it to 5/1! Third, as a comprehensive survey of false positives from RT-PCR tests concluded: “evidence from external quality assessments and real-world data indicate enough a high enough false positive rate to make positive results highly unreliable over a broad range of scenarios” [127]. Because of the myriad RT-PCR tests performed in the USA to screen for/diagnose COVID-19 using different values for Ct and different procedures, a specific number for false positives cannot be obtained at this point in time. Again, these false positives would reduce the 6% number, perhaps substantially. And again, for conservative purposes, we will remain with the 6% number.

Thus, our extremely conservative estimate for risk-benefit ratio is about 5/1. In plain English, people in the 65+ demographic are five times as likely to die from the inoculation as from COVID-19 under the most favorable assumptions! This demographic is the most vulnerable to adverse effects from COVID-19. As the age demographics go below about 35 years old, the chances of death from COVID-19 become very small, and when they go below 18, become negligible.

It should be remembered that the deaths from the inoculations shown in VAERS are short-term only (˜six months for those inoculated initially), and for children, extremely short-term (˜one month) [3]. Intermediate and long-term deaths remain to be identified, and are possible from ADE, autoimmune effects, further clotting and vascular diseases, etc., that take time to develop. Thus, the long-term cost-benefit ratio under the best-case scenario could well be on the order of 10/1, 20/1, or more for all the demographics, increasing with decreasing age, and an order-of-magnitude higher under real-world scenarios! In summary, the value of these COVID-19 inoculations is not obvious from a cost-benefit perspective for the most vulnerable age demographic, and is not obvious from any perspective for the least vulnerable age demographic.

Appendix Da

PROBLEMS WITH TEST CRITERIA FOR DETERMINING COVID-19

Consider the criteria for determining whether an RT-PCR test result is positive for SARS-CoV-2. The CDC instruction (until 1 May 2021) specifies running the RT-PCR tests for 45 amplification cycles. Then, to interpret the data: when all controls exhibit the expected performance, a specimen is considered positive for SARS-CoV-2 if all SARS-CoV-2 marker (N1, N2) cycle threshold growth curves cross the threshold line within 40.00 cycles (< 40.00 Ct). The RNase P may or may not be positive as described above, but the SARS-CoV-2 result is still valid ([103]a).

Many false positives are possible in the upper part of this cycle threshold range, especially in areas of low prevalence. In particular, virus culture has been found to be unfeasible in cases with a Ct value exceeding 33. A prospective cohort study involving the first 100 COVID-19 patients in Singapore also showed that attempts to culture the virus failed in all PCR-positive samples with a Ct value >30” [121]. During mass testing in Germany, it was found “that more than half of individuals with positive PCR test results are unlikely to have been infectious” [122]. Another study found that tests with low specificity (deriving from use of many cycles) cannot provide strong evidence for the presence of an infection [123]. A systematic review of PCR testing concluded “Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high cycle threshold are unlikely to have infectious potential.” [89].

As skeptics have argued, in the buildup of the pandemic, the rapid increase in numbers of COVID-19 cases was due in part to the high values of cycle threshold used in the tests. Unfortunately, the true numbers of false positives will probably be unobtainable if an audit were performed, since these values are not reported with the test results: all currently-available nucleic acid tests for SARS-CoV-2 are FDA-authorized as qualitative tests, and Ct values from qualitative tests should never be used to direct or inform patient management decisions. Therefore, it is not good for laboratories to include Ct values on patient reports [124].

After mass inoculations started, a large number of “breakthrough” cases emerged, and a total of 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported from 46 U.S. states and territories as of April 30, 2021 [18]; the number of reported COVID-19 vaccine breakthrough cases is likely a substantial undercount of all SARS-CoV-2 infections among fully vaccinated persons. The national surveillance system relies on passive and voluntary reporting, and data might not be complete or representative. Many persons with vaccine breakthrough infections, especially those who are asymptomatic or who experience mild illness, might not seek testing [18].

This negative outcome of increased “breakthrough” cases motivated the CDC to change a number of reporting and test procedures and issue new regulations for identifying and investigating hospitalized or fatal vaccine breakthrough cases starting 1 May 2021, stating: “For cases with a known RT-PCR cycle threshold (Ct) value, submit only specimens with Ct value ≤28 to CDC for sequencing. (Sequencing is not feasible with higher Ct values.)”. Thus, the Ct values for sequencing were lowered from the high false positive range allowed during the pandemic buildup to a limit that would eliminate many of these false positives in the ‘breakthrough case’ identification phase [101].

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