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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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.

Warning to anyone who’s had Covid as scientists discover symptoms that can last for TWO YEARS

Authors: Vanessa Chalmers, Digital Health Reporter May 11 2022  May 12 2022

DOCTORS have discovered the symptoms of Covid that can last for two years or more. 

Their research has shown that half of patients admitted to hospital are still likely to have at least one persistent problem two years later.

The study, published in The Lancet Respiratory Medicine, has the longest follow-up period of patients to date. 

Researchers are only able to analyse what symptoms exist after two years given the coronavirus emerged in late 2019.

So it’s possible problems like fatigue and anxiety could stick around even longer.

Lead author Professor Bin Cao, of the China-Japan Friendship Hospital, China, said: “Our findings indicate that for a certain proportion of hospitalised Covid-19 survivors, while they may have cleared the initial infection, more than two years is needed to recover fully from Covid-19.”

The study involved almost 1,200 patients, aged 57 on average, who were infected with the bug in the early phase of the pandemic.

They had all been treated in Wuhan, China, then assessed six months, 12 months and two years after discharge.

Researchers looked at their walking abilities, mental health, quality of life and more.

Covid patients were generally found to be in poorer health than those in the general population two years after infection.

They reported:

  • Fatigue or muscle weakness (31 per cent of Covid patients compared to five per cent in the general population)
  • Sleep difficulties (51 per cent compared with 14 per cent)
  • Pain or discomfort (23 per cent compared with five per cent)
  • Anxiety or depression (12 per cent compared with five per cent)

Joint pain, palpitations, dizziness, and headaches were also more common among previously hospitalised Covid patients.

Not all of those hospitalised were affected, however.

More than half (55 per cent) of participants had at least one symptom of Covid at two years, and were therefore considered “long Covid” patients.

The researchers then compared the long Covid group with the group of participants who had endured Covid, but gotten better. 

Those with long Covid had more pain (35 per cent vs 10 per cent), and mobility issues (five per cent vs one per cent) than their fully recovered counterparts.

Some 13 per cent showed symptoms of anxiety and 11 per cent depression, compared with three per cent and one per cent in non-long Covid patients, respectively. 

The researchers said it’s not possible to say whether problems like these are specific to Covid, or whether other hospital patients experience them.

Long Covid is defined as someone who still battles symptoms beyond four weeks in the UK.

It may be defined as ongoing Covid (four to 12 weeks), or post-Covid syndrome (more than 12 weeks) by medics.

The symptoms may include fatigue, a cough, breathlessness, muscle or joint pain, loss of taste of smell and brain fog.

Post Covid-19 complications: Skin issues, joint pain becoming increasingly common, say experts

People should seek good rehabilitative care, exercise every day, maintain good posture, and follow a healthy diet to manage joint and muscle pain

Authors: By: Lifestyle Desk | New Delhi |

The list of post-Covid complications seems to be only increasing with doctors now saying that there has also been an increase in skin conditions like herpes, and joint pains in patients

What is causing joint issues?

There is about four-five per cent increase in arthritis cases post Covid-19 infection, said Dr Narendra Vaidya, joint replacement surgeon and managing director, Lokmanya Hospital Pune.

“During Covid, inflammatory molecules break muscle protein and decrease its synthesis causing muscle fatigue; this also damages cartilage, causing arthritis. Arthritis can also arise as sequele of steroid and antiviral drugs used to treat Covid-19. Musculoskeletal symptoms like stiffness of joints, muscle pain are commonly seen in post-Covid patients along with decreased muscle strength. Many people complain of joint and muscle pain, and have also come with new onset of autoimmune arthritis,” he said.

According to Dr Vaidya, patients complain of joint pain or arthralgia, muscle pain or myalgia, extreme fatigue, reactive arthritis, and vasculitis (inflammation of the blood vessels). “Joint pain can be temporary or continue for months,” he said.

One more reason to develop joint pain could be the overdose of steroids or a faster. This might develop osteonecrosis of bones, leading to faster degeneration and joint pains, said Dr Richa Kulkarni, chief consulting physiotherapist, KINESIS – Sports Rehab and Physiotherapy Clinic, Pune.

How to prevent and treat the condition?

People should seek good rehabilitative care, exercise every day, maintain good posture, and follow a healthy diet to manage joint and muscle pain, said Dr Vaidya.

What are the skin conditions?

Covid has induced many autoimmune and dormant infections in people with low immunity, such as herpes and warts. “Treatment with monoclonal anti–TNF alpha antibodies can cause herpes. Since the beginning of the pandemic, many people reported herpes, joint pain, and even warts. These problems are commonly seen in females when compared to males. People come with complaints like skin rash, redness, shingles around eyes nose, lips. These infections are common among senior citizens, and pregnant women. Herpes and other skin complications are getting triggered in patients who have a previous history. Do not ignore any signs like rashes, redness of the skin, and patches, seek immediate medical attention,” said Dr Vishwajeet Chavan, orthopedic surgeon, Apollo Spectra Pune.

Dr Saurabh Shah, dermatologist at Bhatia Hospital Mumbai has been seeing about one case of herpes zoster (covid related) every week. “The reason could be low immunity since  Covid attacks the immune system of the body. Herpes Zoster (also known as shingles) virus (Varicella Zoster virus) is present in the body of almost every individual. When our immunity gets compromised or jeopardised, herpes zoster, which lies dormant in the body (dorsal nerve root ganglion), becomes active and flares up. Usually this skin infection is seen in patients with poorly controlled diabetes, patients with chronic renal failure, patients on chemotherapy, post medical and surgical illness and other diseases that compromise our immunity,” he explained.

There is also an uncanny increase in the incidence of urticaria in a lot of patients, said Dr Shah. “These rashes appear as itchy, red, evanescent raised areas on most parts of the body, usually after an infection (post-Covid). These invariably disappear in a few hours,” Dr Shah told indianexpress.com.

By: Lifestyle Desk | New Delhi |
Updated: February 21, 2022 4:22:15 pm

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.”

Vaccinated Up to 15X MORE LIKELY Than Unvaxxed to Develop Heart Inflammation Requiring Hospitalization: Peer Reviewed Study

Authors:  Julian Conradson Published April 25, 2022 at 4:14pm

A new study out of Europe has revealed that cases of heart inflammation that required hospitalization were much more common among vaccinated individuals compared to the unvaccinated.

A team of researchers from health agencies in Finland, Denmark, Sweden, and Norway found that rates of myocarditis and pericarditis, two forms of potentially life-threatening heart inflammation, were higher in those who had received one or two doses of either mRNA-based vaccine – Pfizer’s or Moderna’s.

In all, researchers studied a total of 23.1 million records on individuals aged 12 or older between December 2020 and October 2021. In addition to the increased rate overall, the massive study confirmed the chances of developing the heart condition increased with a second dose, which mirrors other data that has been uncovered in recent months.

From the *peer-reviewed study, which was published by the Journal of the American Medical Association (JAMA):

“Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273.

The risks of myocarditis and pericarditis were highest within the first 7 days of being vaccinated, were increased for all combinations of mRNA vaccines, and were more pronounced after the second dose.”

Also mirroring other data, the study confirmed that young people, especially young males, are the ones who are suffering the worst effects of the experimental jab. Young men, aged 16-24 were an astounding 5-15X more likely to be hospitalized with heart inflammation than their unvaccinated peers.

But it isn’t just young men, all age groups across both sexes – except for men over 40 and girls aged 12-15 – experienced a higher rate of heart inflammation post-vaccination when compared to the unvaxxed.

From The Epoch Times, who spoke with one of the study’s main researchers, Dr. Rickard Ljung:

“‘These extra cases among men aged 16–24 correspond to a 5 times increased risk after Comirnaty and 15 times increased risk after Spikevax compared to unvaccinated,’ Dr. Rickard Ljung, a professor and physician at the Swedish Medical Products Agency and one of the principal investigators of the study, told The Epoch Times in an email.

Comirnaty is the brand name for Pfizer’s vaccine while Spikevax is the brand name for Moderna’s jab.

Rates were also higher among the age group for those who received any dose of the Pfizer or Moderna vaccines, both of which utilize mRNA technology. And rates were elevated among vaccinated males of all ages after the first or second dose, except for the first dose of Moderna’s shot for those 40 or older, and females 12- to 15-years-old.”

Although the peer-reviewed study found a direct link between mRNA based vaccines and increased incident rate of heart inflammation, the researchers claimed that the “benefits” of the experimental vaccines still “outweigh the risks of side effects,” because cases of heart inflammation are “very rare,” in a press conference about their findings earlier this month.

However, while overall case numbers may be low in comparison to the raw numbers and thus technically “very rare,” the rate at which individuals are developing this serious condition has increased by a whopping amount. When considering the fact that 5-15X more, otherwise healthy, young men will come down with the condition – especially since the chances of Covid-19 killing them at that age are effectively zero (99.995% recovery rate) – it’s downright criminal for governments across the world to continue pushing mass vaccinations for everyone.

Dr. Peter McCullough, a world-renowned Cardiologist who has been warning about the long-term horror show that is vaccine-induced myocarditis in young people, certainly thinks so. In his expert opinion, the study does anything but give confidence that the benefits of the vaccine outweigh the risks. In “no way” is that the case, he says. Actually, it’s quite the opposite.

From McCullough, via The Epoch Times:

“In cardiology we spend our entire career trying to save every bit of heart muscle. We put in stents, we do heart catheterization, we do stress tests, we do CT angiograms. The whole game of cardiology is to preserve heart muscle. Under no circumstances would we accept a vaccine that causes even one person to stay sustain heart damage. Not one. And this idea that ‘oh, we’re going to ask a large number of people to sustain heart damage for some other theoretical benefit for a viral infection,’ which for most is less than a common cold, is untenable. The benefits of the vaccines in no way outweigh the risks.”

It’s also worth pointing out that the new study’s findings could be an indicator as to what is driving the massive spike in the excess death rates in the United States and across the world. Correlating exactly with the rollout of the experimental mRNA Covid-19 vaccines, people have been dying at record-breaking rates, especially millennials, who experienced a jaw-dropping 84% increase in excess deaths (compared to pre-pandemic) in the final four months of 2021.

With all the data that has been made available up to this point, there is no denying that the vaccine is at least partially to blame for the spike in severe illness and death, if not entirely. Nevertheless, the CDC, Fauci, Biden, and the rest of the corrupt establishment continue to push mass vaccines, just approved another booster jab (with plans for another already in the works), and are licking their chops to unleash another round of Covid hysteria and crippling restrictions come this fall.

Factors Associated with Post-Acute Sequelae of SARS-CoV-2 (PASC) After Diagnosis of Symptomatic COVID-19 in the Inpatient and Outpatient Setting in a Diverse Cohort

Authors: Sun M. Yoo MD, MPHTeresa C. Liu MD, MPHYash Motwani BSMyung S. Sim DrPH

Nisha Viswanathan MDNathan Samras MDFelicia Hsu MD & Neil S. Wenger MD, MPH 

Journal of General Internal Medicine (2022)

ABSTRACT

Background

The incidence of persistent clinical symptoms and risk factors in Post-Acute Sequelae of SARS-CoV-2 (PASC) in diverse US cohorts is unclear. While there are a disproportionate share of COVID-19 deaths in older patients, ethnic minorities, and socially disadvantaged populations in the USA, little information is available on the association of these factors and PASC.

Objective

To evaluate the association of demographic and clinical characteristics with development of PASC.

Design

Prospective observational cohort of hospitalized and high-risk outpatients, April 2020 to February 2021.

Participants

One thousand thirty-eight adults with laboratory-confirmed symptomatic COVID-19 infection.

Main Measures

Development of PASC determined by patient report of persistent symptoms on questionnaires conducted 60 or 90 days after COVID-19 infection or hospital discharge. Demographic and clinical factors associated with PASC.

Key Results

Of 1,038 patients with longitudinal follow-up, 309 patients (29.8%) developed PASC. The most common persistent symptom was fatigue (31.4%) followed by shortness of breath (15.4%) in hospitalized patients and anosmia (15.9%) in outpatients. Hospitalization for COVID-19 (odds ratio [OR] 1.49, 95% [CI] 1.04–2.14), having diabetes (OR, 1.39; 95% CI 1.02–1.88), and higher BMI (OR, 1.02; 95% CI 1–1.04) were independently associated with PASC. Medicaid compared to commercial insurance (OR, 0.49; 95% CI 0.31–0.77) and having had an organ transplant (OR 0.44, 95% CI, 0.26–0.76) were inversely associated with PASC. Age, race/ethnicity, Social Vulnerability Index, and baseline functional status were not associated with developing PASC.

Conclusions

Three in ten survivors with COVID-19 developed a subset of symptoms associated with PASC in our cohort. While ethnic minorities, older age, and social disadvantage are associated with worse acute COVID-19 infection and greater risk of death, our study found no association between these factors and PASC.

INTRODUCTION

As millions of people recover from COVID-19 amidst the global pandemic, many continue to report an array of persistent symptoms after infection, termed post-acute sequelae of SARS-CoV-2 (PASC). Commonly reported PASC symptoms range from fatigue and dyspnea to “brain fog” and anosmia, with ongoing disability and disruption of work, social, and home lives.1,2,3,4 Centers for Disease Control and Prevention classify the array of symptoms lasting 4 or more weeks after COVID-19 infection as a Post-COVID Condition, which may include long-haul COVID, long COVID, or PASC. Most efforts to describe PASC and factors associated with PASC have focused on hospitalized adult patients1,2,4 and more recently on patient with mild COVID-19 infection treated in the outpatient setting up to 9 months after infection.5,6 Although there are studies that have looked at factors associated with PASC,7 there are no prospective cohort studies to our knowledge that have evaluated the association of ethnicity, social vulnerability, and insurance status with developing PASC. Although COVID-19 has disproportionately impacted racial and ethnic minority groups, previously studied PASC cohorts in the USA have small proportions of Latinx, Black or African American, and Asian American and Pacific Islander (AAPI) patients.5

In April 2020, University of California Los Angeles (UCLA) Health created a COVID Ambulatory Monitoring Program to clinically care for the diverse group of COVID-19 patients discharged from the hospital as well as high-risk COVID-19 patients cared for in the outpatient setting. Patients were eligible from all parts of the UCLA Health system, which includes more than 40 primary care clinics and 20 UCLA Hospitalist services in hospitals across southern California. This COVID-19 program collected standardized clinical data to guide the approach to monitoring and care. Using these patient-reported data combined with clinical information from the electronic health record (EHR), we describe a population-based cohort of patients with symptomatic COVID-19, characterize the timeline of persistent clinical symptoms, and identify factors associated with PASC.

PASC terminology is in evolution and can include a wide range of clinical manifestations including psychiatric manifestations and evidence of organ dysfunction as a result of SARS-CoV-2, including new symptoms or clinical findings that were not evident at the time of acute COVID-19 infection. For our evaluation, we focused on a subset of symptoms associated with PASC as described in the Clinical and Functional Survey (available in Appendix), which we will reference as PASC in our paper.

METHODS

A longitudinal, prospective cohort of adults with laboratory confirmed SARS-CoV-2 infection was enrolled in the UCLA COVID Ambulatory Program starting April 2020. Standardized follow-up was performed to monitor patients with COVID-19 discharged from the two UCLA hospitals, UCLA patients discharged from 20 other local hospitals, and UCLA outpatients who were referred by their primary care providers. COVID-19 patients discharged from the general ward services were approached post-discharge to enroll them in the program. Outpatients with new infections deemed clinically high risk by their primary care providers were referred for enrollment. A questionnaire administered by nurses over the telephone collected information on functional status prior to COVID-19 infection and post-COVID clinical symptoms. Follow-up monitoring continued at 30, 60, and 90 days after hospital discharge for post-discharge patients or date of positive COVID-19 test for outpatients to evaluate for persistent symptoms. A multidisciplinary team of primary care physicians and specialists followed patients to address persistent symptoms or clinical deterioration. The study was approved by the UCLA institutional review board (IRB#20-001358).

A monitoring questionnaire (available in the Appendix) assessed whether the patient felt that his or her health was back to normal. The survey queried baseline function by asking about maximal exertion level prior to COVID-19 infection: vigorous activities such as running, lifting heavy objects, and participating in strenuous sports; moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf; climbing one flight of stairs; walking one block; lifting or carrying groceries; bathing or dressing yourself.8 Functional limitation over the past 4 weeks was assessed using this item during each survey. Perceived cognitive deficits were evaluated with three questions modified from the Perceived Deficits Questionnaire-59 that ask whether patients in the last 4 weeks had trouble getting things organized, had trouble concentrating on things, or forgetting what the patient talked about after a telephone conversation. Lastly, patients were asked about the following symptoms over the past 4 weeks: fever, chills or night sweats; loss of smell or taste; fatigue; shortness of breath; chest pain; numbness or tingling; nausea, vomiting, or diarrhea; muscle aches; and rash.

Demographic characteristics (age, gender, race, ethnicity) were obtained from the EHR, as were a history of diabetes mellitus or organ transplant, body mass index (BMI), Elixhauser comorbidity index,10 and level of medical care required for the initial COVID-19 illness (ambulatory care, emergency room, hospital, and intensive care unit [ICU]). Insurance was collapsed into commercial, Medicare, Medicaid, and none/other. Social Vulnerability Index (SVI) was calculated and split into quartiles.11

Baseline demographic characteristics, functional status, and clinical characteristics were evaluated in the full cohort and compared among patients treated initially in the outpatient setting, in the inpatient setting, and in the ICU. Patients were characterized as having PASC if they noted persistent COVID-19 symptoms on the 90-day post-discharge survey (or the 60-day survey if the 90-day survey was incomplete). Survey attrition flow diagram is included in the Appendix (Supplemental Figure 1). Baseline characteristics of PASC patients in the inpatient and outpatient settings were compared to patients without persisting post-acute symptoms. Among patients with PASC, symptoms were compared at the time of acute infection, 30 days, 60 days, and 90 days, presented separately for patients with PASC who received their initial COVID-19 treatment in the inpatient versus outpatient setting.

Statistical Analysis

Summary statistics (i.e., mean, standard deviation SD, and percentage) for demographics and clinical characteristics are reported for the full cohort. We performed t-tests for a difference in means between groups for age, BMI, and Elixhauser Comorbidity Index and used chi-square tests to test differences in proportions between groups for sex, race/ethnicity, diabetes, transplant, payor status, and baseline functional status. We used a multivariable logistic regression model to evaluate the factors associated with the development of PASC. The pre-specified factors included in the model were demographics (age, sex, race), clinical characteristics (diabetes, BMI, transplant status), insurance type, SVI, COVID-19 care venue, and baseline function. We performed 5 multiple imputations (MI) for Elixhauser (6.0% missingness, and 10.3% unknown) and performed logistic regression analysis for each imputed set. We did not include Elixhauser in the final logistic regression model after finding that it was not statistically significant in those MI sets and the inclusion of imputed Elixhauser in the model did not affect the estimates of odds ratios (ORs) of other factors. In order to further characterize clinical factors associated with PASC, we disaggregated the components of the Elixhauser index and evaluated their individual relationships with PASC using chi-square and Fisher’s exact tests. Factors included in the final model were selected regardless of their statistical significance considering the clinical importance and to examine the effect of socioeconomic status on the PASC outcome. Two-sided P value <0.05 was considered statistically significant and analyses were done using SAS 9.4 (Cary, NC).

RESULTS

Participant Characteristics

Of the 1,296 enrolled in the program between April 2020 to February 2021, 1,038 patients (80.1%) completed follow-up surveys at 30, 60, or 90 days after hospital discharge or outpatient diagnosis and were included in the study. Of the 800 patients treated for COVID-19 in the hospital, 152 (19%) received treatment in the ICU. Of the 238 patients treated as outpatients, 36 (15.1%) received care in the emergency department. The mean age of the cohort was 60 years (interquartile range, 37 to 83) with an even split by gender overall, but more women receiving outpatient care. Thirty percent were White and 42% Latinx. More than one-third of the cohort had diabetes, over 10% had received a solid organ transplant, and mean BMI was nearly 30. Forty-two percent of patients had commercial insurance and mean SVI was 0.46 (interquartile range 0.16 to 0.76). At baseline, most patients could complete vigorous or moderate activities. Men, patients with diabetes, and Latinx patients were more likely to have been admitted to the hospital or the ICU (Table 1).Table 1 Demographics and Clinical Characteristics of COVID-19 PatientsFull size table

Persistent Symptoms

Of the 1038 patients, 309 (29.8%) reported persistent symptoms on the follow-up survey at least 60 days after the acute illness, defined as PASC in this cohort. Of the 800 patients who received treatment for COVID-19 in the hospital, 246 (30.8%) developed PASC whereas 63 (26.5%) of the 238 treated as high-risk outpatients developed PASC.

Symptoms during the acute period of COVID-19 illness were reported on the 30-day survey. Of the PASC patients who completed the 30-day survey (n=231), the most commonly reported symptoms were fatigue in 169 patients (73.2%) followed by shortness of breath in 147 patients (63.6%), fevers and chills in 119 (51.5%), and muscle aches in 117 patients (50.6%). In terms of persistent symptoms at least 60 days after infection, fatigue was the most commonly reported symptom (31.4%), followed by shortness of breath (13.9%), and loss of taste or smell (9.8%). Persistent fever (1.9%) and rash (< 1%) were rare. When comparing hospitalized to outpatient PASC patients, fatigue was the most common persistent symptom in both groups. The next most common symptom in hospitalized patients was shortness of breath (15.4%), whereas it was loss of taste or smell (15.9%) in outpatients (Figure 1A, B).

figure 1
Figure 1

Factors Associated with PASC

In bivariate analyses, factors associated with PASC were different among patients treated for COVID-19 in the inpatient versus outpatient setting. In the outpatient setting, PASC patients were younger, more likely to be White, women, and commercially insured. In the inpatient setting, age and race were unrelated to PASC, and women were more likely to report symptoms consistent with PASC. In both settings, transplant patients were less likely to develop PASC and baseline functional status prior to COVID-19 infection was not related (Table 2).Table 2 Demographics and Characteristics of COVID-19 PASC Cohort and Non-PASC Cohort by Highest Level of CareFull size table

In adjusted analyses, hospitalization for COVID-19 (OR 1.49, 95% confidence interval [CI] 1.04–2.14), having diabetes (OR, 1.39; 95% CI 1.02–1.88), and higher BMI (OR, 1.02; 95% CI 1.0002–1.04) were independently associated with developing PASC. Having Medicaid compared to commercial insurance (OR, 0.49; 95% CI 0.31–0.77) or a history of organ transplant (OR 0.44, 95% CI, 0.26–0.76) was inversely associated with developing PASC. Age, race/ethnicity, SVI, and baseline functional status were not associated with developing PASC (Fig. 2).

figure 2
Figure 2

DISCUSSION

In this prospective cohort of individuals with COVID-19 infection, 30% of patients developed a subset of symptoms associated with PASC. This large, diverse cohort achieved a longitudinal follow-up of 80% of patients after the acute COVID-19 illness. Studying a diverse population treated in a single health system, we are able to control for factors such as access and quality of care often lacking in existing studies.5,12 This health system-based COVID-19 population reveals the startling findings that age, race, and economic disadvantage appear unassociated with development of PASC. This contrasts with COVID-19 infection rates, hospitalizations, and deaths that are disproportionately higher in racial and ethnic minority communities and older people.13,14

Existing prospective studies have not evaluated race and ethnicity and its association with PASC. Sudre et al. found increasing age, female gender, hospitalization, and more than five symptoms in the first week of illness to be associated with PASC, but were unable to analyze the impact of ethnicity due to incomplete data.7 Other studies have described hospitalized patients as more likely to be older, not White, and with lower household incomes compared to outpatients,12 but evaluation of the association between race/ethnicity, SVI, insurance, and PASC were not done.

Current data indicate that ethnic minorities represent a disproportionate number of COVID-19 cases, hospitalizations, and deaths in the USA.13,14,15 Ethnic minorities in the USA diagnosed with COVID-19 were likely to have a greater number of underlying clinical comorbidities,16 lower socioeconomic status,17 loss of health insurance during the pandemic,18,19 and poor access to healthcare. In cohort studies of patients hospitalized for COVID-19, race and ethnicity were not independently associated with in-hospital mortality after adjusting for factors such as age, sex, comorbidities, insurance, and neighborhood deprivation.16,20 This suggests that access to care is an important factor in COVID-19 outcomes. In our study, race and ethnicity was not associated with developing PASC. One possible explanation is that patients had access to the same health system with standardized follow-up. Another possible explanation is that factors that contribute to risks of contracting COVID-19 are not as important in the COVID-19 recovery process and development of PASC. Another factor to consider is whether report of symptoms and expectations for recovery differ across socioeconomic, ethnic, and racial groups and whether the tools used to detect PASC equitably capture these reports.

Existing literature suggests that women were more likely than men to develop PASC,7 whereas our data found a non-statistically significant trend in this direction. It has been suggested this may be due to differences in immunity with a higher prevalence of autoimmune disease in women.21 Diabetes and elevated BMI were associated with developing PASC, which may be due to increased inflammation seen in SARS-CoV-222 potentially leading to microvascular and macrovascular complications.23,24 Interestingly, surviving transplant patients were less likely to develop PASC. The dampened host inflammatory response to COVID-19 for those on immunosuppression agents may play a role, as suggested by a prior study showing solid organ transplant recipients had a faster decline in disease severity over time.25

Surprisingly, patients with commercial insurance had double the likelihood of developing PASC compared to patients with Medicaid. This association will be important to explore further to understand if insurance status in this group is representing unmeasured demographic factors or exposures.

In the acute period of illness, the most commonly reported clinical symptoms among patients who fit our PASC definition were fatigue then shortness of breath, in line with existing studies.1,2 Although fatigue was the most common persistent symptom in hospitalized and non-hospitalized patients, this was followed by loss of sense of smell in outpatients and shortness of breath in inpatients, which is in line with previous studies.3,5 This variation in symptoms at presentation and over time suggests differences in the clinical phenotypes of those with mild to moderate COVID-19 treated in the outpatient setting compared to those with severe COVID-19 requiring hospitalization.

Strengths of our study include a large diverse cohort of COVID-19 patients prospectively followed in a single health system with a large number of organ transplant patients, and standardized longitudinal data to assess symptom evolution over time. Study limitations include potential bias from subjective rating of symptoms and functional status, evaluation of a limited subset of symptoms encapsulated by PASC, not having a comparator group of patients with persistent symptoms after non-COVID hospital admissions, and limited information about pre-existing conditions in our patient population. In addition, survivorship bias may exist where the analysis was limited to individuals that survived to at least 30 days after COVID-19 diagnosis, and referral bias in the outpatient cohort, as only patients deemed clinically high risk were referred to the program, which may affect the generalizability in the outpatient cohort.

CONCLUSION

In this diverse prospective cohort of symptomatic COVID-19 patients treated in the inpatient and outpatient setting, nearly one-third developed a subset of symptoms associated with PASC. The most common symptoms that persisted were different in outpatients compared to inpatients, with fatigue and anosmia in outpatients and fatigue and dyspnea in inpatients. Finally, the lack of relationship between factors related to more serious COVID-19 illness (age, ethnicity, baseline function, and socioeconomic vulnerability) suggests that the long-term effects of COVID-19 may vary from those producing acute illness. These findings, along with variation by insurance status and the protective nature of transplantation, should stimulate additional study to understand the pathophysiologic factors underlying PASC, as well as the tools and methods used to detect PASC. Understanding the effects of long COVID will allow for more effective education among patients and providers, and allow for appropriate healthcare resource utilization in the evaluation and treatment of PASC.

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Only 29% of hospitalized COVID-19 patients fully well one year on: Study

Authors: CNA 24 Apr 2022 08:02AM

PARIS: Not even one in three people have completely recovered from COVID-19 a full year after being hospitalized with the disease, a United Kingdom study indicated on Sunday (Apr 24), warning that long COVID could become a common condition.

The study involving more than 2,300 people also found that women were 33 per cent less likely to fully recover than men.

It also found that obese people were half as likely to fully recover, while those who needed mechanical ventilation were 58 per cent less likely.

The study looked at the health of people who were discharged from 39 British hospitals with COVID-19 between March 2020 and April 2021, then assessed the recovery of 807 of them five months and one year later.

Just 26 per cent reported a full recovery after five months, and that number rose only slightly to 28.9 per cent after a year, according to the study published in the Lancet Respiratory Medicine journal.

“The limited recovery from five months to one year after hospitalisation in our study across symptoms, mental health, exercise capacity, organ impairment and quality of life is striking,” said study co-leader Rachel Evans of the National Institute for Health and Care Research.

The most common long COVID symptoms were fatigue, muscle pain, poor sleep, slowing down physically and breathlessness.

“Without effective treatments, long COVID could become a highly prevalent new long-term condition,” said study co-lead Christopher Brightling of the University of Leicester.

The study, which will be presented at the European Congress of Clinical Microbiology and Infectious Diseases, is ongoing, and will continue to monitor the patients’ health.

Longest Covid infection lasted more than 16 months, tests show

Authors: Michelle Roberts

UK doctors believe they have documented the longest Covid infection on record – a patient they treated who had detectable levels of the virus for more than 16 months, or 505 days, in total.

The unnamed individual had other underlying medical conditions and died in hospital in 2021.

Persistent infections such as this are still rare, say the London medics.

Most people naturally clear the virus, but the patient in question had a severely weakened immune system.

Chronic infections like these need studying to improve our understanding of Covid and the risks it can pose, say experts.

The patient first caught Covid in early 2020. They had symptoms and the infection was confirmed with a PCR test.

They were in and out of hospital many times over the next 72 weeks, for both routine checks and care.

On each occasion – about 50 in all – they tested positive, meaning they still had Covid.

The doctors, from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, say detailed lab analysis revealed it was the same, persistent infection, rather than repeated bouts.

The patient could not shake the infection, even after being given antiviral drugs.

This is different to “long Covid”, where symptoms persist after the infection has gone.

One of the medics who will be presenting the findings at a medical conference – the European Congress of Clinical Microbiology and Infectious Diseases – is Dr Luke Blagdon Snell.

He told the BBC: “These were throat swab tests that were positive each time. The patient never had a negative test. And we can tell it was one continuous infection because the genetic signature of it – the information we got from sequencing the viral genome – was unique and constant in that patient.”

Prolonged infections are rare but important, say the researchers, because they might give rise to new variants of Covid – although that did not happen in this case, or other ones that they studied.

Dr Snell said: “The virus is still adapting to the human host when people are infected for a long time. It might provide an opportunity for Covid to accrue new mutations.

“Some of these patients that we have studied have mutations that have been seen in some of the variants of concern.”

He stressed that none of the nine patients they checked had spawned a new dangerous variant.

Someone with a chronic infection might not be contagious to others, he added.

Dr David Strain from the University of Exeter Medical School, said: “We know that every time the virus replicates, it must reproduce its RNA – equivalent to manually copying a text book. We know if we were to transcribe an entire book we would make mistakes, so too does the virus. Every copy will produce mutations.

“Although Omicron did not arise in these particular individuals, this demonstrates a very clear pathway by which vaccine resistant variants may arise. Whereas with BA.2 we have got lucky, that the mutation is associated with a less severe illness, there is no guarantee that the next iteration will be the same.”