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

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.

The Antiviral Mechanism of Action of Molnupiravir in Humans with COVID-19

“…On visit day 1, levels of viral RNA in NP swabs were higher than that in AN (p = 0.0007) and OP swabs (p = 0.0002), and viral RNA levels tended to be higher in AN swab compared to OP swab (p=0.0593). Similar to our previous studies, viral RNA levels were predictive of Culture-PCR positivity in samples from all three compartments (NP, p = < 0.0001; AN, p = 0.0002; OP p = 0.0007) (Figure 1C) 13 . NP swabs had the greatest proportion of infectious virus positive samples on all visit days assessed (Figure1D).…”

“…The clinical samples utilized in our study were obtained from a previously described Phase 2a randomized, double-blind, placebo-controlled study of multiple doses of molnupiravir in non-hospitalized adults with recently diagnosed COVID-19 9 . The patient population was comprised of unvaccinated adults 18 years of age and older with mild to moderate COVID-19 symptom onset within 7 days and who were PCR positive for SARS-CoV-2 infection within 96 hours at the time of enrollment (day 1) 13 . We evaluated nasopharyngeal (NP) swabs collected on days 1 (baseline), 3 and 5 from 175 participants.…”

Predictors of SARS-CoV-2 RNA From Nasopharyngeal Swabs and Concordance With Other Compartments in Nonhospitalized Adults With Mild to Moderate COVID-19

“…Concerning predictors of viral RNA levels, we found in this population enrolled in the first year of the pandemic (ie, prior to widespread exposure to SARS-CoV-2 or vaccination), shorter prior symptom duration and seronegativity at the time of RNA measurement and older age were all associated with higher NP RNA levels. The association of prior symptom duration and serostatus with NP RNA levels has been observed in other large COVID-19 therapeutics trials conducted early in the pandemic [ 20–22 ], but analyses of associations with age have shown conflicting results [ 21 , 23–26 ]. The association of older age with higher NP RNA even among seropositive participants may reflect unmeasured immune deficiencies with aging such as decreased mucosal interferon responses [ 27–30 ] or less robust or functional humoral responses not captured by examining serostatus as a blunt qualitative measure.…”

Kinetics of SARS-CoV-2 infection biomarkers in a household transmission study

“…However, there are many reasons why the converse (inability to grow virus in culture implying non-infectiousness) may not be true, such as the presence of substances in the specimen that interfere with cultured cell viability or of the ability of virus to infect the cells (e.g. anti-SARS-CoV-2 antibodies 35 ), as well as the relative quantity of the angiotensin converting enzyme-2 receptor, cellular proteases required for virus entry (e.g. TMPRSS-2 36 , 37 ), or other factors that impact the permissiveness of the cultured cells used.…”