Quantifying the Impact of Immune History and Variant on SARS-CoV-2 Viral Kinetics and Infection Rebound: A Retrospective Cohort Study

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Authors James A Hay, Stephen M Kissler, Joseph R Fauver, Christina Mack, Caroline G Tai, Radhika M Samant, Sarah Connolly, Deverick J Anderson, Gaurav Khullar, Matthew MacKay, Miral Patel, Shannan Kelly, April Manhertz, Isaac Eiter, Daisy Salgado, Tim Baker, Ben Howard, Joel T Dudley, Christopher E Mason, Manoj Nair, Yaoxing Huang, John DiFiori, David D Ho, Nathan D Grubaugh, Yonatan H Grad

The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions.

Among individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.3–53.6%) remained potentially infectious (Ct <30) 5 days post detection, with small differences across variants and vaccination status. Only seven viral rebounds (0.7%; N=999) were observed, with rebound defined as 3+days with Ct <30 following an initial clearance of 3+days with Ct ≥30. High antibody titers against the founder SARS-CoV-2 strain predicted lower peak viral loads and shorter durations of infection. Among Omicron BA.1 infections, boosted individuals had lower pre-booster antibody titers and longer clearance times than non-boosted individuals.

SARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines.