Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients

BackgroundSustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. MethodsNinety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. ResultsViral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI [≥] 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

Effectiveness of remdesivir with and without dexamethasone in hospitalized patients with COVID-19

RationaleRemdesivir and dexamethasone reduced the severity of COVID-19 in clinical trials. However, their individual or combined effectiveness in clinical practice remains unknown. ObjectivesTo examine the effectiveness of remdesivir with or without dexamethasone. MethodsWe conducted a multicenter, retrospective cohort study between March 4 and August 29, 2020. Eligible COVID cases were hospitalized patients treated with remdesivir with or without dexamethasone. We applied a Cox proportional hazards model with propensity score matching to estimate the effect of these treatments on clinical improvement by 28 days (discharge or a 2-point decrease in WHO severity score) and 28-day mortality. Measurements and Main ResultsOf 2485 COVID-19 patients admitted between March 4 and August 29, 2020, 342 received remdesivir and 157 received remdesivir plus dexamethasone. Median age was 60 years; 45% were female; 81% were non-white. Remdesivir recipients on room air or nasal cannula oxygen had a faster time to clinical improvement (median 5.0 days [IQR 4.0, 8.0], remdesivir vs. 7.0 days [IQR 5.0, 12.0], control; adjusted hazard ratio (aHR) 1.55 [1.28; 1.87]), yet those requiring higher levels of respiratory support did not benefit. Remdesivir recipients had lower, but statistically insignificant, 28-day mortality (7.6% [23 deaths], remdesivir vs. 14.9% [45 deaths], control). Adding dexamethasone trended toward lower 28-day mortality compared to remdesivir alone (5.1% [8 deaths] vs. 9.2% [17 deaths]; aHR 0.14 [0.02; 1.03]). ConclusionsRemdesivir offered a significantly faster time to clinical improvement among a cohort of predominantly non-white patients hospitalized with COVID-19, particularly with mild-moderate disease. Remdesivir plus dexamethasone may reduce mortality.

Patient trajectories and risk factors for severe outcomes among persons hospitalized for COVID-19 in the Maryland/DC region

BackgroundRisk factors for poor outcomes from COVID-19 are emerging among US cohorts, but patient trajectories during hospitalization ranging from mild-moderate, severe, and death and the factors associated with these outcomes have been underexplored. MethodsWe performed a cohort analysis of consecutive COVID-19 hospital admissions at 5 Johns Hopkins hospitals in the Baltimore/DC area between March 4 and April 24, 2020. Disease severity and outcomes were classified using the WHO COVID-19 disease severity ordinal scale. Cox proportional-hazards regressions were performed to assess relationships between demographics, clinical features and progression to severe disease or death. Results832 COVID-19 patients were hospitalized; 633 (76.1%) were discharged, 113 (13.6%) died, and 85 (10.2%) remained hospitalized. Among those discharged, 518 (82%) had mild/moderate and 116 (18%) had severe illness. Mortality was statistically significantly associated with increasing age per 10 years (adjusted hazard ratio (aHR) 1.54; 95%CI 1.28-1.84), nursing home residence (aHR 2.13, 95%CI 1.41-3.23), Charlson comorbidity index (1.13; 95% CI 1.02-1.26), respiratory rate (aHR 1.13; 95%CI 1.09-1.17), D-dimer greater than 1mg/dL (aHR 2.79; 95% 1.53-5.09), and detectable troponin (aHR 2.79; 95%CI 1.53-5.09). In patients under 60, only male sex (aHR 1.7;95%CI 1.11-2.58), increasing body mass index (BMI) (aHR1.25 1.14-1.37), Charlson score (aHR 1.27; 1.1-1.46) and respiratory rate (aHR 1.16; 95%CI 1.13-1.2) were associated with severe illness or death. ConclusionsA combination of demographic and clinical features on admission is strongly associated with progression to severe disease or death in a US cohort of COVID-19 patients. Younger patients have distinct risk factors for poor outcomes.