Chatterjee, B and Sandhu, HS and Dixit, NM (2022) Modeling recapitulates the heterogeneous outcomes of SARS-CoV-2 infection and quantifies the differences in the innate immune and CD8 T-cell responses between patients experiencing mild and severe symptoms. In: PLoS Pathogens, 18 (6).
|
PDF
PLoS_pat_18-6_2022.pdf - Published Version Download (3MB) | Preview |
Abstract
SARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. Empirical evidence points to the prominent roles of innate immune and CD8 T-cell responses in determining the outcomes. However, how these immune arms act in concert to elicit the outcomes remains unclear. Here, we developed a mathematical model of within-host SARS-CoV-2 infection that incorporates the essential features of the innate immune and CD8 T-cell responses. Remarkably, by varying the strengths and timings of the two immune arms, the model recapitulated the entire spectrum of outcomes realized. Furthermore, model predictions offered plausible explanations of several confounding clinical observations, including the occurrence of multiple peaks in viral load, viral recrudescence after symptom loss, and prolonged viral positivity. We applied the model to analyze published datasets of longitudinal viral load measurements from patients exhibiting diverse outcomes. The model provided excellent fits to the data. The best-fit parameter estimates indicated a nearly 80-fold stronger innate immune response and an over 200-fold more sensitive CD8 T-cell response in patients with mild compared to severe infection. These estimates provide quantitative insights into the likely origins of the dramatic inter-patient variability in the outcomes of SARS-CoV-2 infection. The insights have implications for interventions aimed at preventing severe disease and for understanding the differences between viral variants.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLoS Pathogens |
| Publisher: | Public Library of Science |
| Additional Information: | The copyright for this article belongs to the Author(s). |
| Keywords: | apoptosis; Article; basic reproduction number; CD8+ T lymphocyte; cell killing; cell proliferation; coronavirus disease 2019; human; immune response; in vivo study; innate immunity; mathematical model; nasopharyngeal swab; Severe acute respiratory syndrome coronavirus 2; viral clearance; virus load; virus replication; virus strain; CD8+ T lymphocyte; innate immunity, CD8-Positive T-Lymphocytes; COVID-19; Humans; Immunity, Innate; SARS-CoV-2; Viral Load |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Chemical Engineering |
| Date Deposited: | 22 Sep 2022 09:28 |
| Last Modified: | 22 Sep 2022 09:28 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76626 |
Actions (login required)
 |
View Item |
