Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19
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Publication date
2021-04-23
Authors
Janssen, Nico A.F.
Grondman, Inge
de Nooijer, Aline H.
Boahen, Collins K.
Koeken, Valerie A.C.M.
Matzaraki, Vasiliki
Kumar, Vinod
He, Xuehui
Kox, Matthijs
Koenen, Hans J.P.M.
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Article
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taverne
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.
Keywords
adaptive immunity, biomarkers, COVID-19, cytokines, disease severity, exhaustion markers, flow cytometry, innate immunity, proteomics, Humans, Middle Aged, Cytokines/immunology, Male, COVID-19/blood, Lymphopenia/blood, Inflammation/blood, Biomarkers/blood, Female, Cytokine Release Syndrome/blood, Severity of Illness Index, Immunity, Innate/immunology, Adaptive Immunity/immunology, SARS-CoV-2/immunology, Leukocytes, Mononuclear/immunology, Aged, Taverne, Infectious Diseases, Immunology and Allergy, Journal Article
Citation
Janssen, N A F, Grondman, I, de Nooijer, A H, Boahen, C K, Koeken, V A C M, Matzaraki, V, Kumar, V, He, X, Kox, M, Koenen, H J P M, Smeets, R L, Joosten, I, Brüggemann, R J M, Kouijzer, I J E, van der Hoeven, H G, Schouten, J A, Frenzel, T, Reijers, M H E, Hoefsloot, W, Dofferhoff, A S M, van Apeldoorn, M J, Blaauw, M J T, Veerman, K, Maas, C, Schoneveld, A H, Hoefer, I E, Derde, L P G, van Deuren, M, van der Meer, J W M, van Crevel, R, Giamarellos-Bourboulis, E J, Joosten, L A B, van den Heuvel, M M, Hoogerwerf, J, de Mast, Q, Pickkers, P, Netea, M G & van de Veerdonk, F L 2021, 'Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19', The Journal of infectious diseases, vol. 223, no. 8, pp. 1322-1333. https://doi.org/10.1093/infdis/jiab065