COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Tappe B, Lauruschkat CD, Strobel L, Pantaleón García J, Kurzai O, Rebhan S, Kraus S, Pfeuffer-Jovic E, Bussemer L, Possler L, Held M, Hünniger K, Kniemeyer O, Schäuble S, Brakhage AA, Panagiotou G, White PL, Einsele H, Löffler J, Wurster S (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 13

Article Number: 954985

DOI: 10.3389/fimmu.2022.954985

Abstract

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.

Involved external institutions

Universitätsklinikum Würzburg DE Germany (DE) University of Texas MD Anderson Cancer Center US United States (USA) (US) Julius-Maximilians-Universität Würzburg DE Germany (DE) Klinikum Würzburg Mitte DE Germany (DE) Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (Hans-Knöll-Institut (HKI)) / Leibniz Institute for Natural Product Research and Infection Biology DE Germany (DE) Public Health Wales GB United Kingdom (GB)

How to cite

APA:

Tappe, B., Lauruschkat, C.D., Strobel, L., Pantaleón García, J., Kurzai, O., Rebhan, S.,... Wurster, S. (2022). COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.954985

MLA:

Tappe, Beeke, et al. "COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds." Frontiers in Immunology 13 (2022).

BibTeX: Download