COVID-19 virtual patient cohort suggests immune mechanisms driving disease outcomes
| Autor: | Penelope A. Morel, Rosemary A. Aogo, Vivienne Crowe, Amber M. Smith, Morgan Craig, Amanda P. Smith, Xiaoyan Deng, Adrianne L. Jenner, Courtney L. Davis, Sofia Alfonso |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 medicine.medical_treatment Immunology Inflammation Microbiology 03 medical and health sciences 0302 clinical medicine Immune system Virtual patient Virology Severity of illness Genetics medicine Biology (General) Molecular Biology business.industry Immunosuppression RC581-607 030104 developmental biology 030220 oncology & carcinogenesis Cohort Parasitology medicine.symptom Immunologic diseases. Allergy business CD8 Cohort study |
| Zdroj: | PLoS Pathogens, Vol 17, Iss 7, p e1009753 (2021) |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | 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 thesein silicopatients, 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. |
| Databáze: | OpenAIRE |
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