Survival benefit of remdesivir in hospitalized COVID-19 patients with high SARS-CoV-2 viral loads and low-grade systemic inflammation.

OBJECTIVES: To assess the benefits of remdesivir in hospitalized COVID-19 patients receiving combined immunomodulatory therapy (CIT) with dexamethasone and tocilizumab. METHODS: This was a cohort study of microbiologically confirmed COVID-19 hospitalized patients. The primary outcome was all-cause 28 day mortality. Secondary outcomes were need for invasive mechanical ventilation (IMV) and IMV/death. Subgroup analyses according to SARS-CoV-2 cycle threshold (Ct) values and inflammation biomarkers were performed. Multivariable marginal structural Cox proportional hazards regression models were used to analyse the association between remdesivir therapy and the risk of outcomes of interest. RESULTS: Of 1368 hospitalized patients treated with corticosteroids, 1014 (74%) also received tocilizumab, 866 (63%) remdesivir and 767 (56%) tocilizumab + remdesivir. The 28 day mortality was 9% in the overall cohort, with an adjusted HR (aHR) of 0.32 (95% CI = 0.17-0.59) for patients receiving CIT. In the latter group, the 28 day mortality was 6.5%, with an aHR of 1.11 (95% CI = 0.57-2.16) for remdesivir use and there were no differences in secondary outcomes. The risk of primary and secondary outcomes with remdesivir differed by Ct and C-reactive protein (CRP) levels in patients receiving CIT: for 28 day mortality, the aHR was 0.48 (95% CI = 0.21-1.11) for Ct <25, 0.12 (95% CI = 0.02-0.66) for Ct <25 and <5 day symptom duration and 0.13 (95% CI = 0.03-0.50) for CRP <38 mg/L; for IMV and IMV/death, the aHR was 0.32 (95% CI = 0.13-0.77) and 0.33 (95% CI = 0.17-0.63), respectively, in patients with Ct <25. CONCLUSIONS: The benefits of remdesivir administered with dexamethasone and tocilizumab in hospitalized COVID-19 patients differ depending on Ct and CRP. Remdesivir decreases the risk of mortality and need for IMV in patients with high viral loads and low-grade systemic inflammation.

Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold (CT ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at CT values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions.