Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program (preprint)

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.

A PANDEMIC WITHIN AN EPIDEMIC: EVALUATION OF COVID-19 IN THE OBESE POPULATION

B Conclusion: b This supports the growing body of evidence that obesity has the potential to serve as an independent predictor for outcomes of COVID-19 patients. Evidence has shown increased morbidity and mortality among obese COVID-19 patients. Patients were stratified into healthy weight (BMI < 25), overweight (BMI 25 - 29.9), obese (BMI 30 -39.9), and morbidly obese (BMI > 40) categories. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration (preprint)

The empirically-observed dependence on blood IgG anti-receptor binding domain antibody concentration of SARS-CoV-2 vaccine efficacy against infection has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity and with the observed dependence of vaccine efficacy on antibody concentration and thus is a useful tool in the development of models to relate, for an individual person, risk of breakthrough infection given measured antibody concentration

Individual vaccine efficacy variation with time since mRNA BNT162b2 vaccination estimated by rapid, quantitative antibody measurements from a finger-prick sample (preprint)

We show that an individual’s immune status to Covid-19 can be monitored through quantitative antibody measurements using a method based on centrifugal microfluidics, specifically designed for speed to result (20 min), high throughput (8 samples simultaneously) and accuracy from a finger-prick blood sample. Anti-Receptor Binding Domain (RBD) IgG concentration showed a log-normal distribution with mean decreasing with time following the second vaccination with mRNA BNT162b2 (Pfizer). Using a model for an individual’s antibody concentration-dependent vaccine efficacy allowed comparison with literature data on changing vaccine efficacy against symptomatic disease across a population. Even though the trial was small ( n = 100) the computed population vaccine efficacy was in reasonable agreement with that obtained from a large population survey. The derived parameters for the vaccine efficacy model were in good agreement with those expected from previous studies and from a simple theoretical model. The results and modelling show that the major proportion of breakthrough infections are for people whose antibody concentration is in the tail of the distribution. The results provide strong support for personalized booster programmes that, by targeting people in the tail of the distribution, should be more effective at diminishing breakthrough infection and optimising booster dose supply than a program that simply mandates a booster at a specific post-vaccination time point.

COVID 19 breakthrough infection risk: a simple physical model describing the dependence on antibody concentration (preprint)

The empirically-observed dependence of SARS-CoV-2 vaccine efficacy on antibody concentration has a rational explanation in the statistics of binding of antibody to spike proteins on the virus surface: namely that the probability of protection is the probability of antibody binding to more than a critical number of the spike proteins protruding from the virus. The model is consistent with the observed antibody concentrations required to induce immunity.

The failure of private health services: COVID-19 induced crises in low- and middle-income country (LMIC) health systems.

For decades, governments and development partners promoted neoliberal policies in the health sector in many LMICs, largely motivated by the belief that governments in these countries were too weak to provide all the health services necessary to meet population needs. Private health markets became the governance and policy solution to improve the delivery of health services which allowed embedded forms of market failure to persist in these countries and which were exposed during the COVID-19 pandemic. In this article, we analyse the manifestations of these market failures using data from an assembled database of COVID-19 related news items sourced from the Global Database of Events, Language, and Tone. Specifically, we identify how pre-existing market failure and failures of redistribution have led to the rise of three urgent crises in LMICs: a financial and liquidity crisis among private providers, a crisis of service provision and pricing, and an attendant crisis in state-provider relations. The COVID-19 pandemic has therfore exposed important failures of the public-private models of health systems and provides an opportunity to rethink the future orientation of national health systems and commitments towards Universal Health Coverage.

Validation and Testing of a Method for Detection of SARS-CoV-2 RNA in Healthy Human Stool (preprint)

Background: Fecal shedding of SARS-CoV-2 has raised concerns about transmission through fecal microbiota transplantation (FMT) procedures. While many tests have been authorized for diagnosis of COVID-19 using respiratory samples, no fully validated stool tests for detection of SARS-CoV-2 are currently available. We sought to adapt and validate an available test specifically for detection of SARS-CoV-2 in human stool.Methods: Stool samples were spiked with inactivated SAR-CoV-2 virus for development and validation of the assay. A modified version of the CDC rRT-PCR SARS-CoV-2 test was used for detection of virus. Analytical sensitivity, assay reproducibility, and sample stability under a variety of storage conditions were assessed. We also performed the assay on stool samples collected from known COVID positive individuals.Findings: The lower limit of detection (LoD) of the assay was found to be 3000 viral RNA copies per gram of original stool sample, with 100% detection across 20 replicates assessed at this concentration. Samples were relatively stable in all buffers tested at both 4 o C and ambient temperature, with the exception of storage in STAR buffer at ambient temperature. Assay sensitivity was slightly diminished in low-copy-number samples after a single freeze-thaw cycle at -80°C. Thirty contrived SARS-CoV-2 samples were tested by a second laboratory and were correctly identified as positive or negative in at least one of two rounds of testing. Additionally, we detected SARS-CoV-2 RNA in the stool of known COVID-19 positive individuals using this method.Interpretation: This is a sensitive, reproducible, and validated assay for detection of SARS-CoV-2 RNA in human stool with potential uses in FMT donor screening, sewage monitoring, and further research into the impact of fecal shedding on the epidemiology of this pandemic.Funding: National Institute for Allergy and Infectious Diseases, NIH. Center for Biologics Evaluation and Research, FDA.Declaration of Interests: None to declare.

Recognition and Treatment of Severe COVID-19 in Pregnancy: Lessons from a Cohort of 69 Infected Women and an Evidence-Based Guideline (preprint)

Objectives: To determine clinical and laboratory features of pregnant woman with COVID-19 who require respiratory support. To recommend a management strategy that optimises maternal and fetal outcomes. Design: An observational cohort study of 7000 maternities between 1st March and 1st July 2020. Setting: Five maternity centres across a maternal medicine network in north-central London, UK Population: 69 pregnant women with confirmed acute SARS-COV2 Methods: Review of electronic healthcare records Main Outcome Measures: Clinical and laboratory features, maternal and fetal outcomes. Results: Respiratory support was needed by 15/69 . This cohort was more likely to present with dyspnoea (10/15 vs 10/54, p<0.001), a lower lymphocyte count (0.90.1 vs 1.40.1 x 109 cells/L; p<0.01) and hypokalaemia (3.80.1 vs 4.00.1 mmol/l, p<0.05). Radiological evidence of lung consolidation did not identify women in need of respiratory support. Women on respiratory support underwent childbirth at an earlier gestation than those who did not (36+4 vs 39+5 weeks, p<0.001), and required emergency c-section (6/15 vs 8/54, p<0.05). Childbirth did not improve respiratory function in those with severe disease, with 3 women remaining on invasive ventilation despite childbirth. Conclusions: Routine clinical data can identify pregnant women at risk of severe COVID-19. Pregnant women should be offered the same treatment as non-pregnant patients but iatrogenic childbirth should not be the default for women with severe disease. We propose a management pathway for pregnant women with severe COVID-19.

Validation and testing of a method for detection of SARS-CoV-2 RNA in healthy human stool (preprint)

Background Fecal shedding of SARS-CoV-2 has raised concerns about transmission through fecal microbiota transplantation (FMT) procedures. While many tests have been authorized for diagnosis of COVID-19 using respiratory samples, no fully validated stool tests for detection of SARS-CoV-2 are currently available. We sought to adapt and validate an available test specifically for detection of SARS-CoV-2 in human stool. Methods Stool samples were spiked with inactivated SAR-CoV-2 virus for development and validation of the assay. A modified version of the CDC rRT-PCR SARS-CoV-2 test was used for detection of virus. Analytical sensitivity, assay reproducibility, and sample stability under a variety of storage conditions were assessed. We also performed the assay on stool samples collected from known COVID positive individuals. Findings The lower limit of detection (LoD) of the assay was found to be 3000 viral RNA copies per gram of original stool sample, with 100% detection across 20 replicates assessed at this concentration. Samples were relatively stable in all buffers tested at both 4{degrees}C and ambient temperature, with the exception of storage in STAR buffer at ambient temperature. Assay sensitivity was slightly diminished in low-copy-number samples after a single freeze-thaw cycle at -80{degrees}C. Thirty contrived SARS-CoV-2 samples were tested by a second laboratory and were correctly identified as positive or negative in at least one of two rounds of testing. Additionally, we detected SARS-CoV-2 RNA in the stool of known COVID-19 positive individuals using this method. Interpretation This is a sensitive, reproducible, and validated assay for detection of SARS-CoV-2 RNA in human stool with potential uses in FMT donor screening, sewage monitoring, and further research into the impact of fecal shedding on the epidemiology of this pandemic. Funding National Institute for Allergy and Infectious Diseases, NIH. Center for Biologics Evaluation and Research, FDA.