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Clin Infect Dis . Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates

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  • Clin Infect Dis . Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates


    Clin Infect Dis


    . 2021 Nov 23;ciab968.
    doi: 10.1093/cid/ciab968. Online ahead of print.
    Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates


    Katie R Mollan 1 2 3 , Joseph J Eron 1 2 3 , Taylor J Krajewski 1 3 , Wendy Painter 4 , Elizabeth R Duke 5 , Caryn G Morse 6 , Erin A Goecker 7 , Lakshmanane Premkumar 2 , Cameron R Wolfe 8 , Laura J Szewczyk 4 , Paul L Alabanza 3 , Amy James Loftis 2 , Emily J Degli-Angeli 7 , Ariane J Brown 1 , Joan A Dragavon 7 , John J Won 1 , Jessica Keys 3 , Michael G Hudgens 1 3 , Lei Fang 9 , David A Wohl 2 , Myron S Cohen 1 2 3 , Ralph S Baric 1 , Robert W Coombs 7 , Timothy P Sheahan 1 , William A Fischer 2 10



    Affiliations

    Abstract

    Background: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (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 COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, 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 (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .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 < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001).
    Conclusions: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. 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.
    Clinical trials registration: NCT04405570.

    Keywords: COVID-19; SARS-CoV-2; infectious virus; outpatient; serostatus.

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