ABSTRACT
Background: Guidelines for SARS-CoV-2 have relied on limited data on duration of viral infectiousness and correlation with COVID-19 symptoms and diagnostic testing. Methods: We enrolled ambulatory adults with acute SARS-CoV-2 infection and performed serial measurements of COVID-19 symptoms, nasal swab viral RNA, nucleocapsid (N) and spike (S) antigens, and replication-competent SARS-CoV-2 by culture. We determined average time from symptom onset to a first negative test result and estimated risk of infectiousness, as defined by a positive viral culture. Results: Among 95 adults, median [interquartile range] time from symptom onset to first negative test result was 9 [5] days, 13 [6] days, 11 [4] days, and >19 days for S antigen, N antigen, viral culture growth, and viral RNA by RT-PCR, respectively. Beyond two weeks, viral cultures and N antigen titers were rarely positive, while viral RNA remained detectable among half (26/51) of participants tested 21-30 days after symptom onset. Between 6-10 days from symptom onset, N antigen was strongly associated with viral culture positivity (relative risk=7.61, 95% CI: 3.01-19.2), whereas neither viral RNA nor symptoms were associated with culture positivity. During the 14 days following symptom onset, presence of N antigen (adjusted relative risk=7.66, 95% CI: 3.96-14.82), remained strongly associated with viral culture positivity, regardless of COVID-19 symptoms. Conclusions: Most adults have replication-competent SARS-CoV-2 for 10-14 after symptom onset, and N antigen testing is a strong predictor of viral infectiousness. Within two weeks from symptom onset, N antigen testing, rather than absence of symptoms or viral RNA, should be used to safely discontinue isolation.