SARS-CoV-2 infectious virus, viral RNA in nasopharyngeal swabs, and serostatus of symptomatic COVID-19 outpatients in the United States

Mollan, Katie R.; Eron, Joseph J.; Krajewski, Taylor J.; Painter, Wendy; Duke, Elizabeth R.; Morse, Caryn G.; Goecker, Erin A.; Premkumar, Lakshmanane; Wolfe, Cameron R.; Szewczyk, Laura J.; Alabanza, Paul L.; Loftis, Amy James; Degli-Angeli, Emily J.; Brown, Ariane J.; Dragavon, Joan A.; Won, John J.; Keys, Jessica; Hudgens, Michael G.; Wohl, David A.; Cohen, Myron S.; Baric, Ralph S.; Coombs, Robert W.; Sheahan, Timothy P.; Fischer, William A.

BACKGROUND: SARS-CoV-2 infectious virus isolation in the upper airway of COVID-19 patients is associated with higher levels of viral RNA. However, comprehensive evaluation of the relationships between host and disease factors and infectious, replication competent virus is needed. METHODS: Symptomatic COVID-19 outpatients were enrolled from the United States. 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. FINDINGS: Among 204 participants within one week of reported symptom onset (median=5, IQR 4–5 days), median age was 40 (min-max: 18–82 years), median nasopharyngeal viral RNA was 6.5 (IQR 4.7–7.6 log(10) copies/mL), and 26% had detectable SARS-CoV-2 antibodies at baseline. Infectious virus was recovered in 7% of participants with 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 log(10), 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). INTERPRETATION: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA are likely more reliable markers of infectious virus suppression than subjective measure of COVID-19 symptoms. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. FUNDING: Ridgeback Biotherapeutics, LP and NIH CLINICALTRIALS.GOV IDENTIFIER: NCT04405570