Coronavirus COVID-19 Update for March 3, 2021

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Clinical Reports

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts
Authors conducted two cohort studies from 1 March to 14 June 2020, using routine clinical data in England linked to death data. In study 1, people with an NSAID prescription in the last 3 years from the general population were identified. In study 2, people with rheumatoid arthritis/osteoarthritis were identified. Exposure was defined as current NSAID prescription within the 4 months before 1 March 2020. Cox regression was used to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, 536 423 current NSAID users and 1 927 284 non-users in the general population were included. No evidence of difference in risk of COVID-19 related death was associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, 1 708 781 people with rheumatoid arthritis/osteoarthritis were included, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with the current use of NSAID versus non-use was observed. No evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths was observed. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.
Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
Authors conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalization. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. 146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care. Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.
Effect of a Single High Dose of Vitamin D3on Hospital Length of Stay in Patients With Moderate to Severe COVID-19
In this randomized clinical trial that involved 240 hospitalized patients with moderate to severe COVID-19, a single dose of 200 000 IU of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay (median of 7.0 vs 7.0 days; unadjusted hazard ratio for hospital discharge, 1.07). The study does not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19 in hospitalized patients.
Sequelae in Adults at 6 Months After COVID-19 Infection
A longitudinal prospective cohort of adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was enrolled at the University of Washington with a concurrent cohort of healthy patients in a control group. Electronic informed consent was obtained, and the study was approved by the University of Washington human participants, institutional review board. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline. COVID-19 symptom data were obtained at the time of acute illness or retrospectively recounted at a 30-day enrollment visit. A total of 234 participants with COVID-19 were contacted between August and November 2020 to complete a single follow-up questionnaire between 3 and 9 months after illness onset. Statistical tests for this descriptive analysis were not performed because of the small numbers in each subgroup.

Antiviral Therapeutics and Vaccines

Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine
Authors show that the antibody response to the first vaccine dose in individuals with pre-existing immunity is equal to or even exceeds the titers found in naïve individuals after the second dose. They also show that the reactogenicity is significantly higher in individuals who have been infected with SARS-CoV-2 in the past. Changing the policy to give these individuals only one dose of vaccine would not negatively impact on their antibody titers, and could free up many urgently needed vaccine doses.
Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19
Authors determined the effect of early treatment with antispike neutralizing antibodies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). In the phase 2 portion of a randomized phase 2/3 clinical trial with 577 patients, there was no significant difference in change in viral load with 3 different doses of bamlanivimab monotherapy compared with placebo; treatment with a combination of bamlanivimab and etesevimab significantly decreased SARS-CoV-2 log viral load at day 11 compared with placebo (between-group difference, –0.57 [95% CI, –1.00 to –0.14], P = .01). Treatment with bamlanivimab and etesevimab combination therapy, but not bamlanivimab monotherapy, resulted in a reduction in SARS-CoV-2 log viral load at day 11 in patients with mild to moderate COVID-19.
Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results
World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). Patients were randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.

Diagnostics

Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes —United States, 2020
Using published SARS-CoV-2 transmission parameters, the fraction of SARS-CoV-2 transmissions prevented through serial testing (weekly, every three days, or daily) and isolation of asymptomatic persons compared to symptom-based testing and isolation was evaluated through mathematical modeling using a Reed-Frost model to estimate the percentage of cases prevented (i.e., “effectiveness”) through either outbreak testing alone or outbreak plus non-outbreak testing. The potential effect of simultaneous decreases (by 10%) in the effectiveness of isolating infected individuals when instituting testing strategies was also evaluated. Modeling suggests that outbreak testing could prevent 54% (weekly testing with 48-hour test turnaround) to 92% (daily testing with immediate results and 50% relative sensitivity) of SARS-CoV-2 infections. Adding non-outbreak testing could prevent up to an additional 8% of SARS-CoV-2 infections (depending on test frequency and turnaround time). However, added benefits of non-outbreak testing were mostly negated if accompanied by decreases in infection control practice. When combined with high-quality infection control practices, outbreak testing could be an effective approach to preventing COVID-19 in nursing homes, particularly if optimized through increased test frequency and use of tests with rapid turnaround.

Environmental Studies

Maximizing Fit for Cloth and Medical Procedure Masks to Improve Performance and Reduce SARS-CoV-2 Transmission and Exposure, 2021
CDC conducted experiments to assess two ways of improving the fit of medical procedure masks: fitting a cloth mask over a medical procedure mask, and knotting the ear loops of a medical procedure mask and then tucking in and flattening the extra material close to the face. Each modification substantially improved source control and reduced wearer exposure. These experiments highlight the importance of a good fit to maximize mask performance. There are multiple simple ways to achieve a better fit of masks to more effectively slow the spread of COVID-19.