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- Title
Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19.
- Authors
Janssen, Nico A F; Grondman, Inge; Nooijer, Aline H de; Boahen, Collins K; Koeken, Valerie A C M; Matzaraki, Vasiliki; Kumar, Vinod; He, Xuehui; Kox, Matthijs; Koenen, Hans J P M; Smeets, Ruben L; Joosten, Irma; Brüggemann, Roger J M; Kouijzer, Ilse J E; Hoeven, Hans G van der; Schouten, Jeroen A; Frenzel, Tim; Reijers, Monique H E; Hoefsloot, Wouter; Dofferhoff, Anton S M
- Abstract
The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-γ, interleukin-17, and interleukin-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity.
- Subjects
COVID-19; HEPATOCYTE growth factor; MONONUCLEAR leukocytes; IMMUNE response; STEM cell factor; LYMPHOPENIA
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 8, p1322
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab065