tetano
Editor, Senior Moderator
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[SUP] 1 2 3 [/SUP], Joseph J Eron[SUP] 1 2 3 [/SUP], Taylor J Krajewski[SUP] 1 3 [/SUP], Wendy Painter[SUP] 4 [/SUP], Elizabeth R Duke[SUP] 5 [/SUP], Caryn G Morse[SUP] 6 [/SUP], Erin A Goecker[SUP] 7 [/SUP], Lakshmanane Premkumar[SUP] 2 [/SUP], Cameron R Wolfe[SUP] 8 [/SUP], Laura J Szewczyk[SUP] 4 [/SUP], Paul L Alabanza[SUP] 3 [/SUP], Amy James Loftis[SUP] 2 [/SUP], Emily J Degli-Angeli[SUP] 7 [/SUP], Ariane J Brown[SUP] 1 [/SUP], Joan A Dragavon[SUP] 7 [/SUP], John J Won[SUP] 1 [/SUP], Jessica Keys[SUP] 3 [/SUP], Michael G Hudgens[SUP] 1 3 [/SUP], Lei Fang[SUP] 9 [/SUP], David A Wohl[SUP] 2 [/SUP], Myron S Cohen[SUP] 1 2 3 [/SUP], Ralph S Baric[SUP] 1 [/SUP], Robert W Coombs[SUP] 7 [/SUP], Timothy P Sheahan[SUP] 1 [/SUP], William A Fischer[SUP] 2 10 [/SUP]
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.
. 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[SUP] 1 2 3 [/SUP], Joseph J Eron[SUP] 1 2 3 [/SUP], Taylor J Krajewski[SUP] 1 3 [/SUP], Wendy Painter[SUP] 4 [/SUP], Elizabeth R Duke[SUP] 5 [/SUP], Caryn G Morse[SUP] 6 [/SUP], Erin A Goecker[SUP] 7 [/SUP], Lakshmanane Premkumar[SUP] 2 [/SUP], Cameron R Wolfe[SUP] 8 [/SUP], Laura J Szewczyk[SUP] 4 [/SUP], Paul L Alabanza[SUP] 3 [/SUP], Amy James Loftis[SUP] 2 [/SUP], Emily J Degli-Angeli[SUP] 7 [/SUP], Ariane J Brown[SUP] 1 [/SUP], Joan A Dragavon[SUP] 7 [/SUP], John J Won[SUP] 1 [/SUP], Jessica Keys[SUP] 3 [/SUP], Michael G Hudgens[SUP] 1 3 [/SUP], Lei Fang[SUP] 9 [/SUP], David A Wohl[SUP] 2 [/SUP], Myron S Cohen[SUP] 1 2 3 [/SUP], Ralph S Baric[SUP] 1 [/SUP], Robert W Coombs[SUP] 7 [/SUP], Timothy P Sheahan[SUP] 1 [/SUP], William A Fischer[SUP] 2 10 [/SUP]
Affiliations
- PMID: 35022711
- DOI: 10.1093/cid/ciab968
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.