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

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Pfizer Jab In Young People Only 20% Effective After 60 Days, 0% After 5 Months

Authors:  Zachary Stieber May 14, 2022 The Epoch Times

The Pfizer COVID-19 vaccine turned negatively effective after five months, according to a new study

The Pfizer COVID-19 vaccine turned negatively effective after five months, according to a new study.

Researchers with the U.S. Centers for Disease Control and Prevention (CDC) analyzed test results from sites across the United States and determined that the vaccine was 60 percent effective two to four weeks after 12- to 15-year-olds got the second of the two-dose primary regimen.

But the effectiveness, measured against symptomatic illness, quickly plummeted, hitting 20 percent around month two and zero around month five.

After that, recipients in the age group were more likely to be infected by the disease caused by the CCP (Chinese Communist Party) virus, also known as SARS-CoV-2, the virus causes COVID-19.

Vaccine effectiveness “was no longer significantly different from 0 during month 3 after the second dose,” the researchers wrote in the study, which was published by the Journal of the American Medical Association.

Pfizer, its partner BioNTech, and the CDC didn’t respond to requests for comment.

The analyzed tests were performed between Dec. 26, 2021, and Feb. 21, 2022. Some 47,700 tests among 12- to 15-year-olds were included, with about half being unvaccinated. The testing data was on the Increasing Community Access to Testing, a program funded by the U.S. Department of Health and Human Services that contracts with pharmacy chains to perform drive-through testing. The testing data was supplemented by information in questionnaires filled out by adults with the adolescents.

Limitations of the study included vaccination being self-reported.

The study was funded by the U.S. government.

The study also found that vaccine effectiveness against symptomatic infection plunged quickly for those 5 to 11 years old, starting at 60 percent but hitting 23 percent just one month later.

One way to combat the negative effectiveness, researchers said, was to get a booster dose.

Of the 906 12- to 15-year-olds who got a third, or booster, dose, the effectiveness was measured at 71 percent two to six weeks after receipt.

Other studies, though, show that the protection from a booster, like that from the primary regimen, quickly wanes.

“Given the well-established pattern of waning mRNA VE after 2 doses and early evidence of waning of booster dose protection in adults, monitoring the duration of protection from booster doses in adolescents will be important,” researchers said.

Both the Pfizer and Moderna vaccines are built on messenger RNA (mRNA) technology. VE refers to vaccine effectiveness.

In another study published by the same journal on May 13, New York researchers reported the gap of infection and hospitalization risk between unvaccinated and vaccinated youth narrowing over time, with vaccinated 5- to 11-year-olds being infected at a rate of 62 per 100,000 and unvaccinated being infected at a rate of 70 per 100,000.

That was an incidence rate ratio of 1.1; the rate ratio for 12- to 17-year-olds was 2.

The protection also waned considerably against hospitalization over time, researchers found.

They said that the findings support “efforts to increase vaccination coverage in children and adolescents.”

1 Million COVID Deaths: Here’s The Real Reason Why More People Died From COVID In The United States Than Every Other Country

Authors:  Alicia Powe May 14, 2022 Gateway Pundit

After two years of inundating the public with propaganda and fear surrounding COVID-19, the mainstream media and the federal government turned the page on the manufactured pandemic.

While coronavirus fades from headlines, the number of people purportedly dying from the virus continues to climb.

Over one million Americans have now purportedly died from COVID-19, according to figures published by Our World In Data.

More people died from COVID-19 in the United States than any other developed nation worldwide.

COVID-19 was the third leading cause of death in the U.S. in 2021, following heart disease and cancer, according to new data from the Centers for Disease Control and Prevention.

s the corporate press and the Biden administration raise alarm this week over the high COVID-19 death toll in America, they continue to ignore the elephant in the room.

Americans infected with COVID-19 are not actually dying from the virus, doctors warn.

The United States has the highest COVID death rate in the world because COVID patients are dying in hospitals under the CDC guidelines, Dr. Ben Marble MD., primary care doctor, told The Gateway Pundit in an exclusive interview.

“There’s no question without a doubt that the reason why the United States has the number one highest death toll from COVID is because of all these policies,” he said.

Health practitioners in hospitals “stopped administering all the drugs that work — they stopped the Ivermectin, they stopped the Hydroxychloroquine, and they start protocols that don’t work. They started bad drugs that don’t work like Remdesivir which causes kidney failure in at least 20 percent of people who get it. It’s a bad drug that should be pulled off the market. They didn’t want us doing early treatment — that didn’t make any sense. Early treatment is the cornerstone of all good medicine. Treat everything as early as possible.

In addition to providing every COVID-19 patient with deadly Remdesivir, doctors are required to intubate patients as their health depletes from the drug notorious for causing renal failure.

“They basically hold the patient hostage,” Marble explained. “They won’t let the patient have any visitors. If they complain incessantly, then they sedate the patient. Once you’re sedated, you get intubated. Intubated patients end up dying overnight.”

COVID-19 mandates may have waned, but people are still getting killed in the hospitals and no one is stopping it, Marble fumed.

“All the hospitals in America are still following these protocols that we know don’t work. That’s why the average person doesn’t want to have to go to the hospital right now. A lot of us call them ‘hellspitals’ because of this. They are doing all the wrong things for patients with these failed policies and we all know they’ve failed. The government bureaucracy is stuck on stupid.

After practicing medicine in the emergency for over 15 years, Dr. Marble refused to follow along with new lethal CDC protocols, resigned and founded MyFreeDoctor.Com, where his team provides free treatment for COVID patients.

“I realized Fauci, the CDC, FDA — and everything they were recommending was wrong, the masks, social distancing, the shutdowns — all those things did not work to stop COVID. All they did was make everything worse. It’s proven by the fact that America has the highest death toll in the world,” he said. “We know these are failed policies and we have to quit following them unless we want the highest death toll. Just ignore everything the federal government says and do the opposite.

As information showcasing the inefficacy of COVID vaccines began to permeate the mainstream and Americans became increasingly fed up with the lies, the Biden administration and its propaganda arm diverted the public’s attention to the war with Russia and Ukraine and COVID-19 mandates waned.

“Certainly, they are trying to change the narrative because a lot of the doctors like myself have blown the whistle on this scam and spoken out against Fauci and friends – who are against early treatment while favoring these vaccines,” Dr. Marble said. “The vaccines — normally when an FDA-approved drug harms over 50 people, the normal standard is to pull it off the market at 50 deaths. Yet, according to the Pfizer data that was just revealed, there were over 1,200 deaths in the Pfizer study — there were only like 39,000 people in it. 1200 of them died. The vaccine should have been pulled off the market over a year ago. We’ve blown the whistle on that so the average person doesn’t want to take the vaccine anymore, so they decided, ‘Hey let’s switch the narrative to Ukraine.’”

“Fauci is the architect of all of this.  He is the greatest mass murderer in all the world because he financed the gain of function research. He paid for the creation of COVID-19. That virus is a manmade virus, we know that for a fact. It’s a combination of Sars 1 with parts of HIV, parts of Respiratory Syncytial Virus and mixed the spike protein in there with it. They tried to make it as dangerous as they could to justify the need for fake vaccine gene-editing technology.  The sad thing is they’ve already vaccinated 5 billion people they are going to get to 6 billion by the end of this year. Go to my free doctor.com, that’s where we will try to deliver treatment for free and help as many people as we can. That’s the best we can try to do to help people.”

Washington-based Physician Assistant Scott Miller is unable to practice medicine for the foreseeable future after saving the lives of more than 2,500 Covid patients who were refused adequate care by their doctors or the local hospitals.

It’s clear the CDC has been weaponized against the American public, and they, along with other federal and state government agencies, are complicit in the deaths of now over 1 million Americans and the disruption or destruction of the lives of tens and tens of millions of families across our United States, Miller told The Gateway Pundit in an exclusive interview.

Obviously, Remdesivir is deadly, it shuts down the kidneys. When they were doing the Ebola studies in 2015, Remdesivir was so toxic, so damaging to the organs, it had to be stopped. If they weren’t dying from Ebola, Remdesivir was killing them. Even the WHO deemed it toxic and ineffective and recommended against its use over 16 months ago. Meanwhile, the vaccines are shutting off people’s immune pathways ability to recognize foreign invaders. It’s silencing areas of our immune system that are critical to recognizing a threat. Hell, we could spend a couple hours just talking about antibody-dependent enhancement.”

 Like Miller, medical practitioners who expose the murderous protocols in the hospitals or conspire to save lives continue to be smeared and revoked of their medical licenses.

“The doctors don’t profit, but if they don’t comply with the new protocol, a formal internal investigation would be opened by the hospital as to why they chose to break rank or they would simply be fired. They put so much pressure on the doctors to conform and follow “evidence-based medicine,” Miller said.  “For someone like me, who wasn’t an employee and didn’t work in a clinic, the consequences are far more devastating. I owned my own Pediatrics practice. When the Washington Medical Commission started opening investigations on me, a sane person would have capitulated and stopped speaking out, stopped helping people, and refused to treat them. When they suspended my license, I didn’t just lose my job, I lost the entirety of everything that I worked and sacrificed to build over the last 15 years. I  had hundreds of reasons to not speak out, to not provide care to those who have been abandoned by the medical system, but I had several thousand better reasons to not only share the truth about what is really going on, but to also treat everyone that reached out to me in need.

“The witch hunts by these medical boards across the United States — threatening the livelihood of any provider that chooses to share actual facts, to share truth, to share information that can save people’s lives — has not been addressed nearly enough. If you are a medical provider in the United States, a provider that actually knows the science, your right to free speech hasn’t just been trampled, beaten, stabbed, gang-raped, and then shot, left in the middle of the road for everyone else to see, as a symbol of what happens if you dare speak out against our new normal,” he continued. “If I was going to share how I feel about my experiences over the last 2 years —  on an almost daily basis tasked with trying to figure out how to preserve the lives of people that have been ignored or actively harmed by our medical system — it would not be fit to print. “

The Impact of Initial COVID-19 Episode Inflammation Among Adults on Mortality Within 12 Months Post-hospital Discharge

Authors: Arch G. Mainous III1,2*Benjamin J. Rooks1 and Frank A. Orlando1 May 12, 2022 Frontiers in Medicine

Background: Inflammation in the initial COVID-19 episode may be associated with post-recovery mortality. The goal of this study was to determine the relationship between systemic inflammation in COVID-19 hospitalized adults and mortality after recovery from COVID-19.

Methods: An analysis of electronic health records (EHR) for patients from 1 January, 2020 through 31 December, 2021 was performed for a cohort of COVID-19 positive hospitalized adult patients. 1,207 patients were followed for 12 months post COVID-19 episode at one health system. 12-month risk of mortality associated with inflammation, C-reactive protein (CRP), was assessed in Cox regressions adjusted for age, sex, race and comorbidities. Analyses evaluated whether steroids prescribed upon discharge were associated with later mortality.

Results: Elevated CRP was associated other indicators of severity of the COVID-19 hospitalization including, supplemental oxygen and intravenous dexamethasone. Elevated CRP was associated with an increased mortality risk after recovery from COVID-19. This effect was present for both unadjusted (HR = 1.60; 95% CI 1.18, 2.17) and adjusted analyses (HR = 1.61; 95% CI 1.19, 2.20) when CRP was split into high and low groups at the median. Oral steroid prescriptions at discharge were found to be associated with a lower risk of death post-discharge (adjusted HR = 0.49; 95% CI 0.33, 0.74).

Discussion: Hyperinflammation present with severe COVID-19 is associated with an increased mortality risk after hospital discharge. Although suggestive, treatment with anti-inflammatory medications like steroids upon hospital discharge is associated with a decreased post-acute COVID-19 mortality risk.

Introduction

The impact of coronavirus disease 2019 (COVID-19) has been immense. In terms of directly measured outcomes, as of February, 2022, worldwide more than 5.9 million people have died from directly linked COVID-19 episodes. More than 950,000 direct deaths from COVID-19 have been documented in the United States (1). Some evidence has suggested that some patients with COVID-19 may be at risk for developing health problems after the patient has recovered from the initial episode (24). Common sequelae that have been noted are fatigue, shortness-of-breath, and brain fog. Perhaps more concerningly, in addition to these symptoms, several studies have shown that following recovery from the initial COVID-19 episode, some patients are at risk for severe morbidity and mortality (58). Patients who have recovered from COVID-19 are at increased risk for hospitalization and death within 6–12 months after the initial episode. This morbidity and mortality is typically not listed or considered as a COVID-19 linked hospitalization or death in the medical records and thus are underreported as a post-acute COVID-19 sequelae.

The reason for this phenomenon of severe outcomes as post-acute sequelae of COVID-19 is not well understood. Early in COVID-19 episode, the disease is primarily driven by the replication of SARS-CoV-2. COVID-19 also exhibits a dysregulated immune/inflammatory response to SARS-CoV-2 that leads to tissue damage. The downstream impact of the initial COVID-19 episode is consistently higher in people with more severe acute infection (569). Cytokine storm, hyperinflammation, and multi-organ failure have also been indicated in patients with a severe COVID-19 episode (10). Cerebrospinal fluid samples indicate neuroinflammation during acute COVID-19 episodes (11). Moreover, even 40–60 days post-acute COVID-19 infection there is evidence of a significant remaining inflammatory response in patients (12). Thus, it could be hypothesized that the hyperinflammation that some COVID-19 patients have during the initial COVID-19 episode creates a systemic damage to multiple organ systems (1314). Consequently, that hyperinflammation and the corresponding systemic damage to multiple organ systems may lead to severe post-acute COVID-19 sequelae.

Following from this hyperinflammation, the use of steroids as anti-inflammatory treatments among patients with high inflammation during the initial COVID-19 episode may do more than just help in the initial episode but may act as a buffer to the downstream morbidity and mortality from the initial COVID-19 episode (1415).

The purpose of this study was to examine the relationship between substantial systemic inflammation, as measured by C-reactive protein (CRP), with post-acute COVID-19 sequelae among patients hospitalized with COVID-19. This 12-month mortality risk was examined in a longitudinal cohort of patients who tested positive for COVID-19 as determined by Polymerase Chain Reaction (PCR) testing within a large healthcare system.

Methods

The data for this project comes from a de-identified research databank containing electronic health records (EHR) of patients tested for or diagnosed with COVID-19 in any setting in the University of Florida (UF) Health system. Usage of the databank for research is not considered human subjects research, and IRB review was not required to conduct this study.

Definition of Cohort

The cohort for this study consisted of all adult patients aged 18 and older who were tested for COVID-19 between January 01, 2020 and December 31, 2021 within the UF Health system, in any encounter type (ambulatory, Emergency Department, inpatient, etc.). Although a patient in the cohort could have had a positive test administered in any of these settings, a patient was only included into the cohort if that patient experienced a hospitalization for COVID-19. Since this study included data from the early stages of the pandemic before consistent coding standards for documenting COVID-19 in the EHR had been established, a patient was considered to have been hospitalized for COVID-19 if they experienced any hospitalization within 30 days of a positive test for COVID-19. The databank contained EHR data for all patients in the cohort current through December 31, 2021. COVID-19 diagnosis was validated by PCR. Baseline dates for COVID-19 positive patients were established at the date of their earliest recorded PCR-confirmed positive COVID-19 test. Each patient was only included once in the analysis. For patients with multiple COVID-19 tests, if at least one test gave a positive result, the patient was classified as COVID-19 positive, and the date of their earliest positive COVID-19 test result was used as their baseline date. Patients who did not have a positive COVID-19 test were not included in the analysis. Patients were tested in the context of seeking care for COVID-19; the tests were not part of general screening and surveillance.

Only patients with at least 365 days of follow-up time after their baseline date were retained in the cohort. Patients with more than 365 days of follow-up were censored at 365 days. The cohort was also left censored at the 30-day mark post-hospital discharge to ensure that health care utilization was post-acute and not part of the initial COVID-19 episode of care (e.g., not a readmission).

Inflammation

C-reactive protein (CRP) was used as the measure of inflammation in this study. The UF Health laboratory measured CRP in serum using latex immunoturbidimetry assay. CRP measures were sourced from patient EHR data. The cohort was restricted to only include patients with at least one CRP measurement within their initial COVID-19 episode of care (between the date of their initial positive COVID-19 test and the left-hand censoring date). For patients with multiple measurements of CRP, the maximum value available was used.

Steroids

Intravenous dexamethasone during their initial COVID-19 hospitalization was assessed. Prescriptions for oral steroids (tablets of dexamethasone) that were prescribed either at or post-hospital discharge for their initial COVID-19 episode of care were included into the analysis. Prescriptions were identified using RxNorm codes available in each patient’s EHR.

Severity of Initial COVID-19 Hospitalization

We also measured the severity of the initial episode of COVID-19 hospitalization. This severity should track with the level of inflammation in the initial COVID-19 episode. We used the National Institutes of Health’s “Therapeutic Management of Hospitalized Adults With COVID-19” disease severity levels and definitions (16). The recommendations are based on four ascending levels: hospitalized but does not require supplemental oxygen, hospitalized and requires supplemental oxygen, hospitalized and requires supplemental oxygen through a high-flow device or noninvasive ventilation, hospitalized and requires mechanical ventilation or extracorporeal membrane oxygenation. For this study, because of the general conceptual model of severity moving from no supplemental oxygen to supplemental oxygen to mechanical ventilation, we collapsed the two supplemental non-mechanical ventilation oxygen into one intermediate category of severity.

Outcome Variables

The primary outcome investigated in this study was the 365-day all-cause mortality. Mortality data was sourced both from EHR data and the Social Security Death Index (SSDI), allowing for the assessment of deaths which occurred outside of UF’s healthcare system. When conflicting dates of death were observed between the EHR and SSDI, the date recorded in the patient’s medical record was used. Patients who died within their 365-day follow-up window were censored at the date of their recorded death. The cause of death was not available in the EHR based database and was not routinely and reliably reported in either the SSDI or EHR. We were unable to estimate the cause of death.

Comorbidities

Comorbidities and demographic variables which could potentially confound the association between inflammation represented by CRP and mortality post-acute COVID-19 were collected at baseline for each member of the cohort. Demographic variables included patient age, race, ethnicity, and sex. The Charlson Comorbidity Index was also calculated, accounting for the conditions present for each patient at their baseline. The Charlson Comorbidity Index was designed to be used to predict 1-year mortality and is a widely used measure to account for comorbidities (17).

Analysis

CRP was evaluated using descriptive statistics. We performed a median split of the CRP levels and defined elevated inflammation as a CRP level at or above the median and levels below the median as low inflammation. Additionally, as a way to examine greater separation between high and low inflammation, we segmented CRP levels into tertiles and categorized elevated inflammation as the top tertile and compared it to the first tertile by chi-square tests.

CRP level was also cross classified by severity of COVID-19 hospitalization and associations between the two variables were assessed using one-way ANOVA tests.

Kaplan-Meier curves comparing the survival probabilities of the high and low inflammation groups were created and compared using a log-rank test. Hazard ratios for the risk of death for post-acute COVID-19 complications by COVID-19 status were determined using Cox proportional hazard models. We obtained hazard ratios for mortality based on tertile and median splits of CRP. These analyses were then modified to control for age, sex, race, ethnicity, and the Charlson Comorbidity Index.

Additional analyses stratified by use of steroids were performed to compare the strength of the association between inflammation and death. The proportional hazards assumption was confirmed by inspection of the Schoenfeld residual plots for each variable included in the models and testing of the time-dependent beta coefficients. Analyses were conducted using the survival package in R v4.0.5.

Results

A total of 1,207 patients were included in the final cohort (Table 1). The characteristics of the patients are featured in Table 1. The mean CRP rises with the severity of illness in these COVID-19 inpatients. The mean CRP in the lowest severity (no supplemental oxygen) is 59.4 mg/L (SD = 61.8 mg/L), while the mean CRP in the intermediate severity group (supplemental oxygen) is 126.9 mg/L (SD = 98.6 mg/L), and the mean CRP in the highest severity group (ventilator or ECMO) is 201.2 mg/L (SD = 117.0 mg/L) (p < 0.001). Similarly, since dexamethasone is only recommended for the most severe patients with COVID-19, patients with dexamethasone had higher CRP (158.8 mg/L; SD = 114.9 mg/L) than those not on Dexamethasone (102.8 mg/L; SD = 90/8 mg/L) (p < 0.001).TABLE 1

Table 1. Characteristics of the patients in the cohort.

Figure 1 presents the Kaplan-Meier curves comparing the risk of mortality by inflammation over time. A log-rank test indicated there was a statistically significant difference in survival probabilities between the two groups (p = 0.002).FIGURE 1

Figure 1. All-cause mortality Kaplan-Meier curve comparing individuals with median or greater vs. below median C-reactive protein levels. Log rank test = p.002.

Table 2 shows the relationship between levels of inflammation and mortality post-recovery from COVID-19. In both unadjusted and adjusted analyses, elevated inflammation has a significantly increased risk compared to those with low inflammation in the initial COVID-19 episode. This finding of higher inflammation during the initial COVID-19 hospitalization and increased mortality risk after recovery was similar when CRP was split at the median and when the third tertile of CRP was compared to the first tertile of CRP. The proportional hazards assumption was met when the Schoenfeld plots.TABLE 2

Table 2. All-cause mortality hazard ratios by inflammation and steroid use.

We examined the hypothesized relationship that potentially decreasing inflammation in COVID-19 patients with an initial severe episode may have beneficial downstream effects on post-acute COVID-19 sequelae. Oral steroid prescriptions at discharge among these hospitalized COVID-19 patients were found to be associated with a lower risk of death post-discharge (Table 2).

Discussion

The results of this study reaffirm the importance of post-acute COVID-19 sequelae. This study is the first to show the impact of inflammation in the initial COVID-19 hospitalization episode on downstream mortality after the patient has recovered. This expands our understanding of post-acute COVID-19 sequelae by providing a better concept of why certain patients have post-acute COVID-19 mortality risk.

Previous studies have shown that patients who are hospitalized with COVID-19 have an increased risk of mortality 12 months after recovery (5). Those findings suggest that prevention of COVID-19 hospitalizations is of paramount importance. However, some patients will be hospitalized. The finding that elevated inflammation during the initial hospitalization episode is associated with mortality risk after recovery suggests that it may be worthwhile treating the viral episode but also consider treating the hyperinflammation. The NIH recommendations for care of COVID-19 hospitalized patients recommend steroids only for patients who need supplemental oxygen (16). The finding that the use of steroids prescribed upon discharge from the hospital and the corresponding reduced risk of mortality indicate that treating inflammation after the acute COVID-19 episode may act as a buffer to the downstream mortality risk from the initial COVID-19 episode (1415). Perhaps this requires a reconceptualization of COVID-19 as both an acute disease and potentially a chronic disease because of the lingering risks. Future research is needed to see if ongoing treatment for inflammation in a clinical trial has positive benefits.

There are several strengths and limitations to this study. The strengths of this study include the PCR validated COVID-19 tests at baseline for the cohort. Further, the linked electronic health record allows us to look not only at health care utilization like hospitalizations and both inpatient and outpatient medication but also laboratory tests like CRP levels. The cohort also allows us to have a substantial follow-up time.

In terms of limitations, the first that needs to be considered is that the analysis was based on hospitalized patients seen in one health system with a regional catchment area. Although more than 1200 hospitalized patients with PCR validated COVID-19 diagnoses were included in the analysis, and the cohort was followed for 12 months, the primary independent variable was systemic inflammation which should not be substantially affected by region of the country. Second, the data are observational. Thus, the analyses related to steroids and downstream mortality require a clinical trial to confirm these suggestive findings. Third, we did not have death certificates available to us to compute cause of death. The Social Security Death Index in partnership with the EHR allows us to be confident that the patient died and so we have a strong measure of all-cause mortality but we were unable to determine specific causes of death within this database. Fourth, although there are a variety of other markers of inflammation (e.g., D dimer, IL 6), CRP is one of the most robust measures of systemic inflammation. Moreover, it is much more widely used and was the most prevalent marker among the patients in the study.

In conclusion, hyperinflammation present with severe COVID-19 is associated with an increased mortality risk after hospital discharge. Although suggestive, treatment with anti-inflammatory medications like steroids upon hospital discharge is associated with a decreased post-acute COVID-19 mortality risk. This suggests that treating inflammation may also benefit other post-acute sequelae like long COVID. A reconceptualization of COVID-19 as both an acute and chronic condition may be useful.

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Life-threatening inflammation is turning COVID-19 into a chronic disease

Authors: Chris Melore MAY 13, 2022 Study Finds

Long COVID continues to be a lingering problem for more and more coronavirus patients in the months following their infection. Now, a new study contends that the life-threatening inflammation many patients experience — causing long-term damage to their health — is turning COVID-19 into a chronic condition.

“When someone has a cold or even pneumonia, we usually think of the illness being over once the patient recovers. This is different from a chronic disease, like congestive heart failure or diabetes, which continue to affect patients after an acute episode. We may similarly need to start thinking of COVID-19 as having ongoing effects in many parts of the body after patients have recovered from the initial episode,” says first author Professor Arch G. Mainous III, vice chair for research in the Department of Community Health and Family Medicine at the University of Florida Gainesville, in a media release.

“Once we recognize the importance of ‘long COVID’ after seeming ‘recovery’, we need to focus on treatments to prevent later problems, such as strokes, brain dysfunction, and especially premature death.”

COVID inflammation increases risk of death one year later

The study finds COVID patients experiencing severe inflammation while in the hospital saw their risk of death skyrocket by 61 percent over the next year post-recovery.

Inflammation raising the risk of death after an illness is a seemingly confusing concept. Typically, inflammation is a natural part of the body’s immune response and healing process. However, some illnesses including COVID-19 cause this infection-fighting response to overshoot. Previous studies call this the “cytokine storm,” an event where the immune system starts attacking healthy tissue.

“COVID-19 is known to create inflammation, particularly during the first, acute episode. Our study is the first to examine the relationship between inflammation during hospitalization for COVID-19 and mortality after the patient has ‘recovered’,” Prof. Mainous says.

“Here we show that the stronger the inflammation during the initial hospitalization, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID-19.”

There is a way to stop harmful inflammation

The study examined the health records of 1,207 adults hospitalized for COVID-19 in the University of Florida health system between 2020 and 2021. Researchers followed them for at least one year after discharge — keeping track of their C-reactive protein (CRP) levels. This protein is secreted by the liver and is a common measure of systemic inflammation.

Results show patients with a more severe case of the virus and those needing oxygen or ventilation had higher CRP levels during their hospitalization. The patients with the highest CRP concentrations had a 61-percent increased risk of death over the next year after their release from the hospital.

However, the team did find that prescribing anti-inflammatory steroids after hospitalization lowered the risk of death by 51 percent. Study authors say their findings show that the current recommendations for care after a coronavirus infection need to change. Researchers recommend more widespread use of orally taken steroids following a severe case of COVID.

The Pfizer Clinical Trial: Is There Evidence of Fraud?

Authors:  Michelle Edwards -May 12, 202

Was the clinical trial for Pfizer’s mRNA-based gene-therapy “vaccine” fraudulent? Many are asking that question, and rightly so. Documents released in Nov. 2021 by the FDA as part of the court-mandated document dump show evidence of clinical trial enrollment at one particular trial site happening rapidly and just in time to meet the safety deadline for the FDA’s VRBPAC meeting on Dec. 10, 2020, to discuss Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 jab in individuals 16 and older. Presented on Twitter by Jikkyleaks, the report has raised critical questions.  

The allegedly suspicious-looking clinical trial data surrounds “the biggest recruiter by far,” site 1231 (site 4444 was assigned site id 1231) in Argentina. Adding to the confusion, in five short days before the safety deadline (including a Sunday, 9/27/20), the trial recruited 1,275 of the 4,501 people using site number 4444. In just three weeks, the site recruited 4,501 patients—10% of the entire trial at one site. Overall, Pfizer rapidly recruited roughly 44,000 people for their trial, which took place at 152 locations worldwide and was overseen by numerous investigators, including Dr. Fernando Polack, who led the Argentinian study at Hospital Militar Central

As pointed out by Steve Kirsch, Polack is the Scientific Director of the INFANT Foundation in Buenos Aires. The Vanderbilt-affiliated foundation gives participants the opportunity to conduct biomedical translational research or pediatric rotations at hospitals and medical centers in Buenos Aires. Polack coordinates 26 hospitals in Argentina involving 467 doctors who were instantly recruited into the Pfizer trial. Kirsch said the “new data on Site 1231/4444 looks too good to be true,” but he also noted that all things considered, “it’s quite possible they pulled it off” and coordinated the trial in record time. Noting the infrastructure already in place at Hospital Militar Central, Kirsch referenced an article from Sept. 10, 2020, adding: 

“So if all 26 hospitals participated fully then that’s 57 patients per week per hospital which is possible if the sites have done this before and have a coordination framework for getting all 26 sites up and running at the same time. This means that everyone who was doing something else dropped what they were doing to switch over to the trial all at the same time.”

Still, as Professor Norman Fenton of Queen Mary London University pointed out, the circumstances surrounding the trial are remarkable. Fenton refers to a Substack two-part series on the Site 1231/4444 documents by el gato malo, who wrote that it is “basically impossible,” no matter who you are, to run a clinical trial this quickly. Malo added, “if this really happened, it would be a wonder of the world, and they should publish the process with pride and win 27 different prizes for it.” Malo continued, saying:

“They claim to have enrolled seven days a week for three weeks with zero gaps. Each patient requires a 250-page case report form. The lead investigator seems to have been Fernando Polack.

If indeed, the best way to get things done is to give them to busy people, then this was a great choice because, from the look of things, Fernando is one busy fellah and connected up the wazoo to boot. He also works with Vanderbilt, the FDA, and the Infant Foundation, funded by the Gates Foundation and the NIH.”

Kirsch remarked that Polack is the first author in the New England Journal of Medicine’s (NEJM) article on the Pfizer “vaccine,” titled “Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine.” Interestingly, in the disclosure form for the authors of the NEJM paper, Polack reported receiving personal fees from companies including Pfizer, Janssen, Regeneron, and Merck. Likewise, he disclosed grants from Novavax, Inc. Kirsch (who shared a video on Polack, but noticed no real “smoking gun”) highlighted a few exerts from the Dec. 31, 2020 paper, including:

“About 5,800 volunteers were enrolled, half getting the active vaccine. This is almost 4 times more than the next largest centre in this trial. Amazingly 467 doctors were almost instantly signed up and trained as assistant investigators in the study. Fernando was in command as Pfizer’s Principal Investigator.

Neither Augusto’s pericardial effusion, nor another volunteer’s penile vein thrombosis, appear to have found their way into the reported side effects of this trial.”

Acute hepatitis with autoimmune features after COVID-19 vaccine: coincidence or vaccine-induced phenomenon?

Authors: José M Pinazo-Bandera 1Alicia Hernández-Albújar 1Ana Isabel García-Salguero 2Isabel Arranz-Salas 2Raúl J Andrade 1 3Mercedes Robles-Díaz 1 3

Gastroenterol Rep (Oxf) 2022 Apr 27;10:goac014. doi: 10.1093/gastro/goac014. eCollection 2022.

Introduction

Autoimmune diseases result from a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is characterized by an inflammatory dysregulation that has been associated with the development of autoimmune processes [1].

Molecular mimicry has been suggested as a potential mechanism for these associations as well as ‘bystander activation’ where the infection may lead to activation of antigen presenting cells that may activate autoreactive T-cells, with the production of pro-inflammatory mediators and tissue damage [1].

There is a potential antigenic cross-reactivity between SARS-CoV-2 and human tissue possibly linked to an increase in autoimmune diseases. A recent study showed that antibodies against the spike protein S1 of SARS-CoV-2 had high affinity against some human tissue proteins such as transglutaminase 2 and 3, or myelin basic protein, among others [2].

As both mRNA vaccine (Comirnaty BioNTech BNT162b2 and Spikevax ARNm-1273) and vectorial vaccine (ChAdOx1nCoV-19 Vaxzevria/Covishield) give rise to the production of protein S, the antibodies produced against this protein after vaccination may also trigger autoimmune conditions in predisposed individuals.

Thirteen case reports (including 16 patients) have recently reported an association between COVID-19 vaccines and acute hepatitis development [3–15].

Here we report two new cases of liver injury possibly related to COVID-19 vaccination.

Case 1

A 77-year-old woman developed intense malaise, vomiting and disorientation 2 days after receiving the second dose of Comirnaty vaccine and was hospitalized the following day. She did not have a history of autoimmune disorders. She denied alcohol drinking and was on long-term therapy with bromazepam, losartan, and omeprazole. Her previous liver tests back in 2020 were normal.

Physical examination was normal except for scleral icterus. Liver test showed acute hepatocellular injury: total bilirubin (TB) 3.1 mg/dL (reference, <1 mg/dL), aspartate aminotransferase (AST) 474 U/L (reference, <40 UI/L), alanine aminotransferase (ALT) 552 U/L (reference, <40 U/L), and alkaline phosphatase (ALP) 159 U/L (reference, <117 U/L). Immunoglobulin G levels were within normal ranges (reference, 800–1,600 mg/dL), while anti-nuclear antibody and anti-mitochondrial antibody M2 were detected with 1/160 and 1/40 titre, respectively. Human leukocyte antigen (HLA) testing was positive for HLA-DR4. All the other possible aetiologies were ruled out.

The patient was discharged and closely monitored. Due to increased transaminase levels, she underwent a liver biopsy (Supplementary Figure 1.1), which showed findings compatible with autoimmune hepatitis (AIH).

Prednisone 60 mg/day on tapering dose was initiated and 3 weeks later liver test had markedly improved. Azathioprine was added 2 months later, but it had to be withdrawn due to rash. Prednisone was then replaced by budesonide 9 mg/day. Five months after onset, transaminases were within the normal range; however, the subject was hospitalized with neurologic symptoms in relation to brain lesions in both hemispheres of probable infectious origin and died 1 month later.

Case 2

A 23-year-old man presented with mononucleosis syndrome-like symptoms and jaundice at the emergency room, 10 days after receiving the second dose of Spikevax vaccine. He did not suffer from previous autoimmune disorders. He denied having taken any conventional drug treatments as well as alcohol consumption.

Physical examination was unremarkable except for scleral icterus. Liver tests showed acute hepatocellular injury: TB 2.3 mg/dL, AST 702 U/L, ALT 587 U/L, and ALP 202 U/L. Immunoglobulin G levels were minimally elevated (1,647 mg/dL), while autoantibodies resulted as negative. HLA testing was positive for HLA-DR3. Serology ruled out viral causes and abdominal ultrasonography was normal. After admission to the hospital, a thoracic-abdominal scan was performed and revealed generalized lymphadenopathy.

He underwent a liver biopsy (Supplementary Figure 1.2), which showed findings compatible with AIH.

Prednisone 60 mg/day on tapering dose was initiated and 1 month later lymphadenopathies were undetectable and liver test had significantly improved. Three months after onset, transaminases were within the normal range and he is still on low-dose prednisone 10 mg/day.

Discussion

These new cases of liver injury compatible with AIH, which developed post COVID-19 vaccination, along with 13 prior published case reports (16 patients) reinforce that this association could be more than coincidental. In the previously published case reports, all the patients, except three, were females and their age ranged from 35 to 80 years [3–15]. Twelve of these patients received one of the mRNA vaccines [35–121415], while four patients received vectorial vaccines [41213]. In 6 of the 16 patients, liver biopsy revealed infiltration with eosinophils [347914] and IgG levels were increased in 12 cases [4–1215].

Fourteen reported patients were successfully treated with prednisolone whereas two died due to acute liver failure [412] (Table 1).

Table 1.

Characteristics of patients with liver injury after SARS-CoV-2 vaccine (published cases and two new cases)

AuthorVaccineDoseDays until clinical onsetGenderAgeLiver-injury patternAutoimmune disease historyAuto- antibodiesIgGBiopsySteroid responseDeath
Compatible (Yes/No)Eosinophils infiltration (Yes/No)
Bril et al. [3Comirnaty BioNTech BNT162b2 1st 13 35 Hep None ANAAnti-dsDNA Normal Yes Yes Yes No 
Rela et al. [4(2 cases) ChAdOx1nCoV-19 Covishield (both patients) NA 20 38 NAa None ANA High Yes Yes Yes No 
NA 16 65 NAa None NA NA Yes Yes No Yes 
Rocco et al. [5Comirnaty BioNTech BNT162b2 2nd 80 Hep Hashimoto disease ANA High Yes No Yes No 
Londoño et al. [6Spikevax, ARNm-1273 2nd 41 Hep None ANASMASLALC-1 High Yes No Yes No 
Tan et al. [7Spikevax, ARNm-1273 1st 35 56 Hep None ANASMA High Yes Yes Yes No 
McShane et al. [8Spikevax, ARNm-1273 1st 71 Hep None SMA High Yes No Yes No 
Ghielmet-ti et al. [9Spikevax, ARNm-1273 1st 63 Hep None ASMAANCAANA High Yes Yes Yes No 
Garrido et al. [10Spikevax, ARNm-1273 1st 14 65 Hep None ANA High Yes No Yes No 
Avci et al. [11Comirnaty BioNTech BNT162b2 NA 14 61 Mix Hashimoto disease ANASMA High Yes No Yes No 
Erard et al. [12(3 cases) Spikevax, ARNm-1273(two first patients)ChAdOx1nCoV-19 Vaxzevria(third one) 2nd 10 80 NAa None Negative High Yes No Yes No 
1st 21 73 NAa None Negative High Yes No Yes No 
1st 20 68 NAa None Negative High Yes No No Yes 
Clayton-Chubb et al. [13ChAdOx1nCoV-19 Vaxzevria 1st 26 36 Hep None ANA Normal Yes No Yes No 
Lodato et al. [14Comirnaty BioNTech BNT162b2 1st 15 43 NAa None Negative Normal Yes Yes Yes No 
Vuille-Lessard et al. [15Spikevax, ARNm-1273 1st 76 Hep Hashimoto disease ANA High Yes No Yes No 
Pinazo et al. (2 cases) Comirnaty BioNTech BNT162b2(First one)Spikevax, ARNm-1273(second one) 2nd 77 Hep None ANAAMANegative Normal Yes Yes Yes Yesb 
2nd 10 23 Hep None High Yes No Yes No 

M, male; F, female; NA, not available; Hep, hepatocellular; Mix, mixed; IgG, immunoglobulin G; ANA, anti-nuclear antikor; SMA, smooth muscle antibodies; dsDNA, double-stranded DNA antibodies; LC1, liver sitozol antibody; anti-SLA, soluble liver antigen antibodies; ANCA, anti-neutrophil cytoplasmic antibodies; AMA, anti-mitochondrial antibodies.a

ALP (alkaline phosphatase) not available.b

The patient died due to an extrahepatic cause (brain lesions in both hemispheres of probable infectious origin).Open in new tab

In both cases of the present study, a number of laboratory (including HLA testing) and histological features supported the autoimmune nature of the liver injury. In our first case, the short period elapsed after vaccine administration, the laboratory and histopathological findings (showing moderate liver fibrosis), the positive HLA-DR4, and the response to therapy suggest unmasking of AIH by the vaccine. However, in our second case, the medical history negative for liver and autoimmune diseases, the short time interval after vaccination, the typical onset of symptoms to which was added generalized lymphadenopathy, the elevated immunoglobulin G levels, the positive HLA-DR3, histopathological findings with absence of liver fibrosis, and the response to therapy reinforce the hypothesis of SARS-CoV-2 vaccine as a trigger of an autoimmune liver injury debut. We realize that there are no pathognomonic (laboratory or histological) features of AIH, but the appropriate exclusion of viral and metabolic causes of liver injury makes the autoimmune mechanisms the more likely explanation for both cases.

Taking into account the large number of vaccinated subjects worldwide, the suspicion of vaccine-related AIH carries important clinical implications. It is unknown whether prolonged immunosuppression would be required in these cases or whether re-exposure to a new dose of COVID-19 vaccine might trigger fulminant liver injury. Nevertheless, the risk of receiving another dose must be balanced against the risk of contracting SARS-CoV-2 infection. In addition, it remains unclear whether patients who have developed liver injury after vaccination with one type of vaccine can receive other COVID-19 vaccine with a different mechanism of action.

Post COVID-19 vaccination, AIH has been rarely reported so far [3–15], which might be due to either minimal awareness of this disease or because patients without jaundice often do not seek medical attention. However, given the growing number of cases compatible with AIH reported after SARS-CoV-2 vaccination, regulators should consider the inclusion of this potential adverse event in the label of COVID-19 vaccines.

In conclusion, clinicians should be aware of the potential association between the vaccines and the onset of immune mediated disorders such as AIH. However, this rare complication should not discourage people from getting vaccinated.

References

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Rare cases of COVID returning pose questions for Pfizer pill

Authors: MATTHEW PERRONE May 9, 2022 AP NEWS

As more doctors prescribe Pfizer’s powerful COVID-19 pill, new questions are emerging about its performance, including why a small number of patients appear to relapse after taking the drug.

Paxlovid has become the go-to option against COVID-19 because of its at-home convenience and impressive results in heading off severe disease. The U.S. government has spent more than $10 billion to purchase enough pills to treat 20 million people.

But experts say there is still much to be learned about the drug, which was authorized in December for adults at high risk of severe COVID-19 based on a study in which 1,000 adults received the medication.

WHY DO SOME PATIENTS SEEM TO RELAPSE?

Doctors have started reporting rare cases of patients whose symptoms return several days after completing Paxlovid’s five-day regimen of pills. That’s prompted questions about whether those patients are still contagious and should receive a second course of Paxlovid.

Last week, the Food and Drug Administration weighed in. It advised against a second round because there’s little risk of severe disease or hospitalization among patients who relapse.

Dr. Michael Charness reported last month on a 71-year-old vaccinated patient who saw his symptoms subside but then return, along with a spike in virus levels nine days into his illness.

Charness says Paxlovid remains a highly effective drug, but he wonders if it might be less potent against the current omicron variant. The $500 drug treatment was tested and OK’d based on its performance against the delta version of the coronavirus.

“The ability to clear the virus after it’s suppressed may be different from omicron to delta, especially for vaccinated people,” said Charness, who works for Boston’s VA health system.

Could some people just be susceptible to a relapse? Both the FDA and Pfizer point out that 1% to 2% of people in Pfizer’s original study saw their virus levels rebound after 10 days. The rate was about the same among people taking the drug or dummy pills, “so it is unclear at this point that this is related to drug treatment,” the FDA stated.

Some experts point to another possibility: The Paxlovid dose isn’t strong enough to fully suppress the virus. Andy Pekosz of Johns Hopkins University worries that could spur mutations that are resistant to the drug.

“We should really make sure we’re dosing Paxlovid appropriately because I would hate to lose it right now,” said Pekosz, a virologist. “This is one of the essential tools we have to help us turn the corner on the pandemic.”

HOW WELL DOES PAXLOVID WORK IN VACCINATED PEOPLE?

Pfizer tested Paxlovid in the highest-risk patients: unvaccinated adults with no prior COVID-19 infection and other health problems, such as heart disease and diabetes. The drug reduced their risk of hospitalization and death from 7% to 1%.

But that doesn’t reflect the vast majority of Americans today, where 89% of adults have had at least one shot. And roughly 60% of Americans have been infected with the virus at some point.

“That’s the population I care about in 2022 because that’s who we’re seeing — vaccinated people with COVID — so do they benefit?” asked Dr. David Boulware, a University of Minnesota researcher and physician.

There’s no clear answer yet for vaccinated Americans, who already have a hospitalization rate far below 1%.

That may come from a large, ongoing Pfizer study that includes high-risk vaccinated people. No results have been published; the study is expected to wrap up in the fall.

Pfizer said last year that initial results showed Paxlovid failed to meet the study’s goals of significantly resolving symptoms and reducing hospitalizations. It recently stopped enrolling anyone who’s received a vaccination or booster in the past year, a change Boulware says suggests those patients aren’t benefitting.

At a minimum, the preliminary data should be released to federal officials, Boulware said. “If the U.S. government is spending billions of dollars on this medicine, what’s the obligation to release that data so that they can formulate a good policy?”

CAN PAXLOVID BE USED TO HELP PREVENT COVID-19 INFECTION?

Pfizer recently reported that proactively giving Paxlovid to family members of people infected with COVID-19 didn’t significantly reduce their chances of catching it. But that’s not the end of the story. Pfizer is studying several other potential benefits of early use, including whether Paxlovid reduces the length and severity of COVID-19 among households.

“It’s a high bar to protect against infection but I’d love to see data on how Paxlovid did against severe disease because it may be more effective there,” said Pekosz.

Editor of the British Medical Journal tells the FDA about Serious Concerns over Pfizer Trial Data Integrity

And the lack of FDA oversight

Dr Doshi in an associate professor of pharmaceutical health at the University of Maryland School of Pharmacy, as well as a senior editor at the British Medical Journal. “His research focuses on the drug approval process, how the risks and benefits of medical products are communicated, and improving the credibility and accuracy of evidence synthesis and biomedical publications.”

In the most recent Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee meeting in the US (6 April 2022), Peter dialled in to the Open Public Hearing Session. This is where members of the public can present their own information to the FDA. The committee was meeting to discuss considerations for the use of COVID-19 vaccine boosters and the process for COVID-19 vaccine strain selection to address current and emerging variants.

Peter told the FDA about Brook Jackson, a whistle-blower from Ventavia, which ran Pfizer’s vaccine trials. He discussed how unblinding of trial participants seems to have occurred and how this creates serious concerns about data integrity.

Last November, The BMJ reported the disclosures of a whistle-blower named Brook Jackson, who worked for Ventavia, a contract research company that ran three of the clinical trial sites for Pfizer’s vaccine. Jackson alleged the company had falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events. She provided The BMJ with company emails, internal documents, text messages, photos and recordings of her conversations with company employees.

This photo, for example, shows vaccine packaging materials that are only supposed to be seen by unblinded staff, just left out in the open.

And unblinding may have occurred on a far wider scale. Here you can see the document containing the instructions Ventavia staff were given to file each trial participant’s randomization and drug assignment confirmation sheet into each participant’s chart. This contained unblinded information.

Unblinding, as I think everybody knows, creates serious concerns about data integrity. Once this massive error was discovered, Ventavia asked staff to go through each and every chart to take out the randomization and drug assignment confirmations. You can see here an email from Ventavia’s COO reacting after discovery of the problem: they had not even realized that the drug assignment confirmation contained unblinding information.

In the heat of a pandemic, it’s not hard to imagine that corners were cut and mistakes were made. Some mistakes are benign, but others carry serious consequences to data integrity. One hopes Ventavia is an extreme outlier, but we need more than just hope. We need evidence that the data were dealt with properly. We need regulatory oversight. But despite whistleblower Brook Jackson’s direct complaint to the FDA, FDA never inspected Ventavia. In fact, FDA only inspected 9 of the trial’s 150-plus sites before approving the vaccine. Just 9 sites. And Pfizer continues to use Ventavia for trials.

What about Moderna? FDA had over a year and inspected just one – ONE – of the trial’s 99 sites. How can FDA feel confident in the Moderna data based on a 1% sample?

Data integrity requires adequate regulatory oversight. Trustworthy science requires data transparency. It’s been over a year, but anonymised participant level data remain inaccessible to doctors, researchers, and the public. The public paid for these products, and the public takes on the balance of benefits and harms post vaccination. The public has a right to data transparency, and FDA has an obligation to act. Thank you.

The video for the meeting is below. Peter Doshi’s statement starts at 5:34:44 but all of the public presentations are interesting and these begin at around 5:15.

FDA Investigating Reports Of COVID Relapses Following Use Of Pfizer’s Pill

Authors: Zachary Stieber  May 8, 2022

The U.S. Food and Drug Administration (FDA) is investigating reports of relapses among people who took Pfizer’s COVID-19 pill.

The FDA “is evaluating the reports of viral load rebound after completing paxlovid treatment and will share recommendations if appropriate,” an agency spokesperson told The Epoch Times in an email.

In a recent preprint case report, Veterans Affairs researchers reported that a 71-year-old male who took the pill, also known as nirmatrelvir, experienced a “rapid and progressive reduction” in the viral load of SARS-CoV-2, the virus that causes COVID-19.

But four days after completing the treatment course, there was a “surprising rebound of viral load and symptoms,” they reported.

The report “highlights the potential for recurrent, symptomatic SARS-CoV-2 replication after successful early treatment” with the pill, the researchers said.

A number of others have said they saw renewed symptoms after taking paxlovid.

In the FDA’s evaluation (pdf) of data on paxlovid, which the agency cleared on an emergency basis in 2021, the agency reported that in an ongoing phase 2/3 trial run by Pfizer, several participants “appeared to have a rebound” in viral load five to nine days after completing their treatment courses.

In light of the new reports, additional analyses of the paxlovid trial data were performed and showed that 1 to 2 percent of the patients had one or more positive COVID-19 tests after testing negative, or an increase in the amount of viral load, after completing the treatment, Dr. John Farley of the FDA said in an interview the agency published on May 4.

“This finding was observed in patients treated with the drug as well as patients who received placebo, so it is unclear at this point that this is related to drug treatment,” he said, adding that, at this time, the reports “do not change the conclusions from the paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.”

As part of the authorization agreement, the FDA said Pfizer must later submit information regarding “prolonged virologic shedding or rebound in clinical trials.”

Pfizer did not respond to a request for comment.

The company told Bloomberg that the rate of rebound in its trial was not higher among people who took paxlovid than in people who took a placebo.

“This suggests the observed increase in viral load is unlikely to be related to paxlovid,” the company said.

Dr. Clifford Lane, deputy director for clinical research at the National Institute of Allergy and Infectious Diseases, told the outlet that the agency will study the issue, calling it “a priority.”

Lane and the agency did not return queries.

The FDA authorized paxlovid for the treatment of mild to moderate COVID-19 in Americans 12 years or older. To get the pill, a person must test positive for COVID-19 and be deemed at high risk of progressing to severe disease.