Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Effect of Early Treatment with Ivermectin among Patients with COVID-19
Researchers conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2–positive adults recruited from 12 public health clinics in Brazil. Patients who had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19.

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19A Randomized Clinical Trial
In this bayesian randomized clinical trial that included 1557 patients, antiplatelet therapy with either aspirin or a P2Y12 inhibitor, compared with no antiplatelet therapy, resulted in a 95.7% posterior probability of futility with regard to the odds of improvement in organ support–free days within 21 days. Among critically ill patients with COVID-19, there was a low likelihood that treatment with an antiplatelet agent provided improvement in organ support–free days within 21 days.
Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19
The objective of this study is to evaluate if early aspirin use in hospitalized patients with moderate COVID-19 is associated with lower odds of in-hospital mortality. In a cohort study of 112,269 patients with moderate COVID-19, early aspirin use during the first day of hospitalization was associated with lower 28-day in-hospital mortality and pulmonary embolism incidence when compared with patients who did not receive early aspirin. This study suggests that early aspirin use may be associated with lower odds of in-hospital mortality among hospitalized patients with moderate COVID-19; these findings warrant further study in a randomized clinical trial that includes diverse patients with cardiovascular comorbidities.
Prone positioning of patients with moderate hypoxaemia due to covid-19: multicenter pragmatic randomized trial (COVID-PRONE)
The objective of this study was to assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomized and 248 were included in the analysis. Patients were randomized 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomization was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomization. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomized to prone positioning and standard of care. Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning

Antiviral Therapeutics and Vaccines

U.S. Food and Drug Administration authorized a second booster dose of either the Pfizer-BioNTech or the Moderna COVID-19 vaccines for older people and certain immunocompromised individuals.
The U.S. Food and Drug Administration authorized a second booster dose of either the Pfizer-BioNTech or the Moderna COVID-19 vaccines for older people and certain immunocompromised individuals. The FDA previously authorized a single booster dose for certain immunocompromised individuals following completion of a three-dose primary vaccination series. This action will now make a second booster dose of these vaccines available to other populations at higher risk for severe disease, hospitalization and death. Emerging evidence suggests that a second booster dose of an mRNA COVID-19 vaccine improves protection against severe COVID-19 and is not associated with new safety concerns.
Second Booster Vaccine and Covid-19 Mortality in Adults 60 to 100 Years Old
The rapid emergence of the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus-2 led to a global resurgence of coronavirus disease 2019 (Covid-19). Israeli authorities approved a 4th Covid-19 vaccine dose (second-booster) for individuals aged 60 and above who received a first booster dose four or more months earlier. Evidence regarding the effectiveness of a second-booster dose in reducing mortality due to Covid-19 is warranted. This retrospective cohort study included all members of Clalit Health Services, aged 60 to 100, eligible for the second-booster. Mortality due to Covid-19 among participants who received the second-booster was compared with participants who received one booster dose. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between the second-booster and death due to Covid-19 while adjusting for demographic factors and coexisting illnesses. A total of 563,465 participants met the eligibility criteria. Of those, 328,597 (58%) received a second-booster dose during the 40-day study period. Death due to Covid-19 occurred in 92 second-booster recipients and in 232 participants who received one booster dose (adjusted hazard ratio 0.22; 95% confidence interval 0.17 to 0.28). This study demonstrates a substantial reduction in Covid-19 mortality by the second-booster in eligible subjects.
Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults — VISION
Vaccine effectiveness against COVID-19–associated emergency department/urgent care visits was 24% after 1 Jansen dose, 54% after 2 Jansen doses, and 79% after 1 Janssen/1 mRNA dose, compared to 83% after 3 mRNA doses. Vaccine effectiveness for the same strategies against COVID-19–associated hospitalization was 31%, 67%, 78%, and 90% respectively. All eligible persons should receive recommended COVID-19 booster doses to prevent moderate to severe COVID-19. Adult Janssen primary vaccine recipients should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later.
Efficacy of Bacillus Calmette-Guérin vaccination against respiratory tract infections in the elderly during the Covid-19 pandemic
In this multicenter, placebo-controlled trial, study researchers randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval, .65–2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval, .71–1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection.
Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes
This study examined whether SARS-CoV-2 vaccination during pregnancy was associated with adverse pregnancy outcomes. In this population-based retrospective cohort study that included 157,521 deliveries in Sweden and Norway, SARS-CoV-2 vaccination during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with risk of preterm birth (adjusted hazard ratio [aHR], 0.98), stillbirth (aHR, 0.86), small for gestational age (adjusted odds ratio [aOR], 0.97), low Apgar score (aOR, 0.97), or neonatal care admission (aOR, 0.97). In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy was not associated with an increased risk of adverse pregnancy outcomes.

Diagnostics

Use of At-Home COVID-19 Tests — United States, August 23, 2021–March 12, 2022
A rapid increase in U.S. at-home test use occurred between the SARS-CoV-2 Delta- and Omicron-predominant periods; at-home test use was lower among persons who self-identified as Black, were aged ≥75 years, had lower incomes, and had a high school level education or less. Commonly reported reasons for using at-home tests included exposure concerns and symptoms. COVID-19 testing, including at-home tests, along with prevention measures such as quarantine and isolation when warranted, wearing a well-fitted mask when recommended after a positive test or known exposure, and staying up to date with vaccination can help reduce the spread of COVID-19. Providing reliable and low-cost or free at-home test kits to underserved populations with otherwise limited access to COVID-19 testing could assist with continued prevention efforts.