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

Authors :
Beeke Tappe
Chris D. Lauruschkat
Lea Strobel
Jezreel Pantaleón García
Oliver Kurzai
Silke Rebhan
Sabrina Kraus
Elena Pfeuffer-Jovic
Lydia Bussemer
Lotte Possler
Matthias Held
Kerstin Hünniger
Olaf Kniemeyer
Sascha Schäuble
Axel A. Brakhage
Gianni Panagiotou
P. Lewis White
Hermann Einsele
Jürgen Löffler
Sebastian Wurster
Source :
Frontiers in Immunology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

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.

Details

Language :
English
ISSN :
16643224
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.722827bb9fc46acb787b360a554ab51
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2022.954985