Περίληψη:
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. © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Συγγραφείς:
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.
Λέξεις-κλειδιά:
biological marker; cytokine, adaptive immunity; aged; blood; cytokine release syndrome; female; human; immunology; inflammation; innate immunity; lymphocytopenia; male; middle aged; mononuclear cell; severity of illness index; virology, Adaptive Immunity; Aged; Biomarkers; COVID-19; Cytokine Release Syndrome; Cytokines; Female; Humans; Immunity, Innate; Inflammation; Leukocytes, Mononuclear; Lymphopenia; Male; Middle Aged; SARS-CoV-2; Severity of Illness Index
