| Literature DB >> 33524124 |
Nico A F Janssen1, Inge Grondman1, Aline H de Nooijer1, Collins K Boahen1, Valerie A C M Koeken1, Vasiliki Matzaraki1, Vinod Kumar1,2, Xuehui He3, Matthijs Kox4, Hans J P M Koenen3, Ruben L Smeets3,5, Irma Joosten3, Roger J M Brüggemann6, Ilse J E Kouijzer1, Hans G van der Hoeven4, Jeroen A Schouten4, Tim Frenzel4, Monique H E Reijers7, Wouter Hoefsloot7, Anton S M Dofferhoff8, Marjan J van Apeldoorn9, Marc J T Blaauw10, Karin Veerman11, Coen Maas12, Arjan H Schoneveld12, Imo E Hoefer12, Lennie P G Derde13, Marcel van Deuren1, Jos W M van der Meer1, Reinout van Crevel1, Evangelos J Giamarellos-Bourboulis14, Leo A B Joosten1, Michel M van den Heuvel7, Jacobien Hoogerwerf1, Quirijn de Mast1, Peter Pickkers4, Mihai G Netea1,15, Frank L van de Veerdonk1.
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.Entities:
Keywords: COVID-19; adaptive immunity; biomarkers; cytokines; disease severity; exhaustion markers; flow cytometry; innate immunity; proteomics
Year: 2021 PMID： 33524124 PMCID： PMC7928798 DOI： 10.1093/infdis/jiab065
Source DB: PubMed Journal: J Infect Dis ISSN： 0022-1899 Impact factor: 5.226