COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infecte...

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Bibliographic Details
Published in:PLoS pathogens 2021-07, Vol.17 (7), p.e1009753-e1009753
Main Authors: Jenner, Adrianne L, Aogo, Rosemary A, Alfonso, Sofia, Crowe, Vivienne, Deng, Xiaoyan, Smith, Amanda P, Morel, Penelope A, Davis, Courtney L, Smith, Amber M, Craig, Morgan
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Biomarkers
CD8 antigen
Clinical trials
Coronaviruses
COVID-19
Cytokine storm
Depletion
Granulocytes
Hospitalization
Immune response
Infections
Inflammatory diseases
Interferon
Interleukin 6
Kinetics
Lymphocytes
Lymphocytes T
Macrophages
Mathematical models
Medicine and Health Sciences
Monocytes
Neutrophils
Parameter estimation
Patients
Phenotypes
Robustness (mathematics)
Severe acute respiratory syndrome coronavirus 2
Viral infections
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Summary:To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009753