Coronavirus COVID-19 Update for February 22, 2021

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Clinical Reports

Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study
The objective of this study was to evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.
Multisystem Inflammatory Syndrome in Children (MIS-C) Interim Guidance
The CDC issued a Health Advisory on May 14, 2020, that outlines the following case definition for MIS-C:

- An individual aged <21 years presenting with fever,1 laboratory evidence of inflammation,2 and evidence of clinically severe illness requiring hospitalization, with multisystem (≥2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological); AND

- No alternative plausible diagnoses; AND

- Positive for current or recent SARS-CoV-2 (COVID-19) infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms.

Antiviral Therapeutics and Vaccines

Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 InfectionThe COVID A to Z Randomized Clinical Trial
There is limited evidence regarding early treatment of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to mitigate symptom progress. The objective of this study was to examine whether high-dose zinc and/or high-dose ascorbic acid reduce the severity or duration of symptoms compared with usual care among ambulatory patients with SARS-CoV-2 infection. This multicenter, single health system randomized clinical factorial open-label trial enrolled 214 adult patients with a diagnosis of SARS-CoV-2 infection confirmed with a polymerase chain reaction assay who received outpatient care in sites in Ohio and Florida. The trial was conducted from April 27, 2020, to October 14, 2020. Patients were randomized in a 1:1:1:1 allocation ratio to receive either 10 days of zinc gluconate (50 mg), ascorbic acid (8000 mg), both agents, or standard of care. The primary endpoint was the number of days required to reach a 50% reduction in symptoms, including severity of fever, cough, shortness of breath, and fatigue (rated on a 4-point scale for each symptom). Secondary end points included days required to reach a total symptom severity score of 0, cumulative severity score at day 5, hospitalizations, deaths, adjunctive prescribed medications, and adverse effects of the study supplements. A total of 214 patients were randomized, with a mean (SD) age of 45.2 (14.6) years and 132 (61.7%) women. The study was stopped for a low conditional power for benefit with no significant difference among the 4 groups for the primary end point. Patients who received usual care without supplementation achieved a 50% reduction in symptoms at a mean (SD) of 6.7 (4.4) days compared with 5.5 (3.7) days for the ascorbic acid group, 5.9 (4.9) days for the zinc gluconate group, and 5.5 (3.4) days for the group receiving both (overall P = .45). There was no significant difference in secondary outcomes among the treatment groups. In this randomized clinical trial of ambulatory patients diagnosed with SARS-CoV-2 infection, treatment with high-dose zinc gluconate, ascorbic acid, or a combination of the 2 supplements did not significantly decrease the duration of symptoms compared with standard of care.
D ecreased SARS-CoV-2 viral load following vaccination
Beyond their substantial protection of individual vaccines, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. In this preprint the authors analyze positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine. They find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.

Epidemiology

Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence
After initially containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many European and Asian countries had a resurgence of COVID-19 consistent with a large proportion of the population remaining susceptible to the virus after the first epidemic wave. By contrast, in Manaus, Brazil, a study of blood donors indicated that 76% (95% CI 67–98) of the population had been infected with SARS-CoV-2 by October, 2020. High attack rates of SARS-CoV-2 were also estimated in population-based samples from other locations in the Amazon Basin—eg, Iquitos, Peru 70%. The estimated SARS-CoV-2 attack rate in Manaus would be above the theoretical herd immunity threshold (67%), given a basic case reproduction number (R0) of 3. In this context, the abrupt increase in the number of COVID-19 hospital admissions in Manaus during January 2021 (3431 in Jan 1–19, 2021, vs 552 in Dec 1–19, 2020) is unexpected and of concern. After a large epidemic that peaked in late April, 2020, COVID-19 hospitalizations in Manaus remained stable and fairly low for 7 months from May to November, despite the relaxation of COVID-19 control measures during that period. This commentary provides four non-mutually exclusive possible explanations for these observations.

Environmental Studies

Operational Considerations for Schools
Schools play an important role in educating students about disease prevention within their homes and communities. Additionally, many children and adolescents rely on key services provided by schools, such as school meal programs, psychosocial support, disability services, and outreach for vulnerable populations. Schools are considered safe havens for children who might be experiencing various forms of abuse or violence. This document provides suggestions for mitigating risks for COVID-19 transmission in schools in low-resource international settings and describes considerations associated with each mitigation measure, including considerations for secondary impacts such as food insecurity and exposure to violence and for students who are at high risk for dropping out of school, so that schools may safely resume and sustain operations. The proposals are presented by mitigation practice (respiratory hygiene (use of masks), hand hygiene, and physical distancing). This document does not supersede any national or local government laws, regulations, or mandates; rather, it is intended to complement existing or proposed mitigation measures.