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

BACKGROUNDSARS-CoV-2 has evolved subvariants since the emergence of the Omicron variant in 2021. Whether these changes impact viral shedding and transmissibility is not known.METHODSPOSITIVES 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, semiquantitative viral culture to detect shedding of replication-competent virus, and whole-genome sequencing to classify subvariants. Our predictor of interest was Omicron subvariants: 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 symptoms are a valid marker for ending isolation.RESULTSThe 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 (12-14 days), and median days to negative viral culture (4-8 days) were similar across Omicron subvariants. Number and duration of symptoms were also similar. For all subvariants, a sizeable percentage (range 27.5%-56.0%) shed replication-competent virus after fever resolution and improvement of symptoms.CONCLUSIONDespite 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.FUNDINGNIH (U19 AI110818, R01 AI176287, K24 HL166024), the Massachusetts Consortium on Pathogen Readiness, and the Massachusetts General Hospital Department of Medicine.