Infectious SARS-CoV-2 Virus in Symptomatic COVID-19 Outpatients: Host, Disease, and Viral Correlates
Katie R Mollan, Joseph J Eron, Taylor J Krajewski, Wendy Painter, Elizabeth R Duke, Caryn G Morse, Erin A Goecker, Lakshmanane Premkumar, Cameron R Wolfe, Laura J Szewczyk, Paul L Alabanza, Amy James Loftis, Emily J Degli-Angeli, Ariane J Brown, Joan A Dragavon, John J Won, Jessica Keys, Michael G Hudgens, Lei Fang, David A Wohl, Myron S Cohen, Ralph S Baric, Robert W Coombs, Timothy P Sheahan, William A Fischer 2nd, Katie R Mollan, Joseph J Eron, Taylor J Krajewski, Wendy Painter, Elizabeth R Duke, Caryn G Morse, Erin A Goecker, Lakshmanane Premkumar, Cameron R Wolfe, Laura J Szewczyk, Paul L Alabanza, Amy James Loftis, Emily J Degli-Angeli, Ariane J Brown, Joan A Dragavon, John J Won, Jessica Keys, Michael G Hudgens, Lei Fang, David A Wohl, Myron S Cohen, Ralph S Baric, Robert W Coombs, Timothy P Sheahan, William A Fischer 2nd
Abstract
Background: While SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection.
Methods: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay.
Results: Among 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001).
Conclusions: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion.
Clinicaltrialsgov identifier: NCT04405570.
Keywords: COVID-19; SARS-CoV-2; infectious virus; outpatient; serostatus.
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Source: PubMed