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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
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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 5

Mechanistic underpinning of more rapid clearance of SARS-CoV-2 during reinfection versus initial infection.

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Mechanistic underpinning of more rapid clearance of SARS-CoV-2 during re...
Initial infection and reinfection were documented for 67 individuals in the NBA cohort. (A) Examples of data and model fits for infection and reinfection in the same individual. (B) As measured from the data, peak viral load of reinfection against peak viral load of first infection. In all cases, the variant causing the reinfection was Omicron, and the variant causing the first infection was either Delta or a pre-Delta variant. The mean peak viral load was around 0.5 log lower for second infection (t test statistic = 2.26, P = 0.0254). (C) Proportion of infections cleared for reinfection (blue) and first infections (gray) over time, as measured from the data. Median time to clearance is 7.5 versus 12 days since detection. (D) Box plots of estimated individual parameters for infection and reinfection that are significantly different between the 2 groups (P < 0.05 for Mann-Whitney U test with Bonferroni adjustment for multiple comparisons). During reinfection with Omicron, the rate that susceptible cells convert to a refractory state is higher and the onset of the late immune response occurs significantly earlier. (E–H) Mean viral load (E), number of refractory cells (F), number of susceptible cells (G), and late clearance rates over time (H) for the 2 groups as predicted by mechanistic model.

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