Open AccessCOVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes
Author(s) -
Adrianne L. Jenner,
Rosemary A. Aogo,
Sofia Alfonso,
Vivienne Crowe,
Xiaoyan Deng,
Amanda Smith,
Penelope A. Morel,
Courtney L. Davis,
Amber M. Smith,
Morgan Craig
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009753
Subject(s) - cohort , immune system , immunology , cd8 , disease , covid-19 , inflammation , monocyte , phenotype , medicine , biology , cohort study , genetics , infectious disease (medical specialty) , gene
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.