Viral kinetics of SARS-CoV-2 following onset of COVID-19 in symptomatic patients infected with the ancestral strain and omicron BA.2 in Hong Kong: a retrospective observational study.

Background: Assessment of viral kinetics of SARS-CoV-2 can inform on host immune responses to the virus and on the viral transmission potential. We aimed to characterise viral shedding kinetics by age, virus type, and clinical outcome, and to examine the potential effect of vaccination on viral shedding.

Methods: In this retrospective observational study, we analysed longitudinal data on cycle threshold (Ct) values of reverse-transcription quantitative PCR (RT-qPCR) assays of upper respiratory tract samples from symptomatic patients with COVID-19. Patients who were confirmed with COVID-19 with at least one Ct value of the RT-qPCR test available within 28 days after symptom onset, and discharged or died at the time of the analysis, were included in the study. Patients were isolated in hospitals in Hong Kong during three major epidemic waves dominated by the ancestral strain or omicron BA.2. We modelled the temporal trajectories of viral burden in these patients. Electronic medical records of the patients with COVID-19 were retrieved and linked to the patients' epidemiological information obtained from contact tracing. Patients who were infected outside Hong Kong, infected with variants other than the ancestral strain or omicron BA.2, not reporting any COVID-19 related symptoms, still hospitalised at the time of analysis, missing information on age, time of symptom onset, infection severity, vaccination or clinical outcome, infected more than once, or treated with nirmatrelvir-ritonavir or molnupiravir were excluded from analysis. The main outcome of this study is the temporal change of SARS-CoV-2 viral burden measured by Ct values of RT-qPCR tests in symptomatic patients with COVID-19.

Findings: Among 22 461 symptomatic patients with COVID-19 confirmed from July 1, 2020, to May 22, 2022, the estimated viral burden from a random-effects model indicated a longer duration of viral shedding in patients with more severe outcomes of infection (mean difference 13·1 days, 95% CI 12·9-13·3, for fatal vs mild-to-moderate) and in older patients (5·2, 5·0-5·5, for age ≥80 years vs 0-18 years). Vaccinated individuals with a breakthrough infection with the omicron BA.2 variant had a generally lower viral burden and shorter durations of viral shedding (mean difference of 2-4 days) over 4 weeks after onset than unvaccinated individuals infected with omicron BA.2, particularly in patients whose last dose of COVID-19 vaccine was received ≤90 days before symptom onset. Marginal differences in viral burden following symptom onset and the duration of viral shedding were observed between unvaccinated individuals infected with the ancestral strain and omicron BA.2.

Interpretation: The viral kinetics since symptom onset characterised for symptomatic patients with COVID-19 in our study show that previously vaccinated or younger individuals, or those with a milder infection, shed fewer viruses in a shorter period, implying possible transmission dynamics of SARS-CoV-2 and protective mechanisms of vaccination against infection and severe outcomes.

Funding: Hong Kong Health and Medical Research Fund and Hong Kong Collaborative Research Fund.