Dysregulated Innate and Adaptive Immune Responses Discriminate Disease Severity in COVID-19
The Journal of Infectious Diseases, 2021
Janssen N., Grondman I., de Nooijer A., Boahen C., Koeken V., Matzaraki V., Kumar V., He X., Kox M., Koenen H., Smeets R., Joosten I., Brüggemann R., Kouijzer I., van der Hoeven H., Schouten J., Frenzel T., Reijers M., Hoefsloot W., Dofferhoff A., van Apeldoorn M., Blaauw M., Veerman K., Maas C., Schoneveld A., Hoefer I., Derde L., van Deuren M., van der Meer J., van Crevel R., Giamarellos-Bourboulis E., Joosten L., van den Heuvel M., Hoogerwerf J., de Mast Q., Pickkers P., Netea M., van de Veerdonk F.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
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.