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

TL;DR

This study found that despite evolving Omicron subvariants of SARS-CoV-2, viral shedding and infection dynamics remain largely unchanged.

Contribution

The study provides empirical evidence that Omicron subvariants do not significantly alter viral shedding or infectiousness duration.

Findings

Viral RNA levels and shedding duration were similar across Omicron subvariants.

A significant proportion of individuals shed replication-competent virus after symptom resolution.

Symptoms are not reliable indicators of infectiousness for ending isolation.

Abstract

SARS-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.

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, 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.

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 (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.

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.

NIH (U19 AI110818, R01 AI176287, K24 HL166024), the Massachusetts Consortium on Pathogen Readiness, and the Massachusetts General Hospital Department of Medicine.

The course of COVID-19 infection, including duration of likely infectiousness and symptoms, has not changed across Omicron variants. Symptoms, which form the basis for current public health guidance, are not a reliable reflection of likely infectiousness.

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