Virologic characteristics of SARS-CoV-2 infection across evolving omicron subvariants

The SARS-CoV-2 virus has evolved subvariants since the emergence of the omicron variant in 2021. Whether these changes impact viral shedding and transmissibility is not known. POSITIVES is a prospective longitudinal cohort of individuals with mild SARS-CoV-2 infection. Ambulatory, immunocompetent participants who did not receive antivirals self-administered 6 anterior nasal swabs over 15 days. Samples were analyzed by qPCR to quantify viral RNA, semi-quantitative viral culture to detect shedding of replication-competent virus, and whole genome sequencing to classify subvariants. Our predictor of interest was omicron subvariant: BA.1x, BA.2x, BA.4/5x, XBB.x and JN.x. Outcomes included RNA levels and duration of shedding replication-competent virus. We additionally explored whether the duration and severity of symptom correlated with duration of viral shedding and whether symptoms are a valid marker for ending isolation. The median peak nasal SARS-CoV-2 RNA (6.0-6.3 log10 RNA copies/mL), median days to peak RNA (4-5 days), median days to undetectable viral RNA (10-12 days) and median days to negative viral culture (3.5-6 days) was similar across omicron subvariants. Number and severity of symptoms were also similar. For all subvariants, a sizeable percentage (range 28.2-52.0%) shed replication-competent virus after fever resolution and improvement of symptoms. Despite ongoing viral evolution, key aspects of viral dynamics of SARS-CoV-2 infection, including the duration of shedding replication-competent virus, have not substantially changed across omicron subvariants. Replication-competent shedding of these subvariants is detected for a large proportion of people who meet criteria for ending isolation. This work was supported by the National Institutes of Health (NIH), the Massachusetts Consortium on Pathogen Readiness, and the Massachusetts General Hospital Department of Medicine.