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Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses
Katherine Owens, … , Shadisadat Esmaeili, Joshua T. Schiffer
Katherine Owens, … , Shadisadat Esmaeili, Joshua T. Schiffer
Published April 4, 2024
Citation Information: JCI Insight. 2024;9(9):e176286. https://doi.org/10.1172/jci.insight.176286.
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Research Article Infectious disease Virology

Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses

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Abstract

The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of interindividual variability. We identified 6 distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate, and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1,510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection as well as by an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during Omicron infection, following vaccination, and following reinfection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.

Authors

Katherine Owens, Shadisadat Esmaeili, Joshua T. Schiffer

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Figure 1

Viral kinetics by variant in the National Basketball Association cohort from June 2020 to January 2022.

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Viral kinetics by variant in the National Basketball Association cohort ...
In total, 1,510 SARS-CoV-2 infections are documented from this cohort. (A–D) Time series are stratified by variant with individual viral loads plotted in color, the median viral load plotted with a solid black line, and the 25th and 75th percentiles plotted in dashed black lines for prevariant of concern viruses (A), Alpha (B), Delta (C), and Omicron infections (D). (E) Bubble plot showing the relationship between variant of infection and vaccination status of the individual. Both the color and the size of the circle indicate the number of infections in each category. (F) Additional information about infections includes age, presence of symptoms, reinfection status, and preinfection antibody titer following vaccination.

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