학술논문
COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds.
Document Type
Academic Journal
Author
Tappe B; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Lauruschkat CD; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Strobel L; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Pantaleón García J; Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.; Kurzai O; Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; Rebhan S; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Kraus S; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Pfeuffer-Jovic E; Department of Pulmonary Medicine, Missionsärztliche Klinik Würzburg, Würzburg, Germany.; Bussemer L; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Possler L; Department of Internal Medicine, Main-Klinik Ochsenfurt, Würzburg, Germany.; Held M; Department of Pulmonary Medicine, Missionsärztliche Klinik Würzburg, Würzburg, Germany.; Hünniger K; Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; Kniemeyer O; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; Schäuble S; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; Brakhage AA; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; Department of Microbiology and Molecular Biology, Institute of Microbiology, Friedrich Schiller University, Jena, Germany.; Panagiotou G; Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans -Knöll- Institute, Jena, Germany.; White PL; Public Health Wales, Microbiology Cardiff, Wales, United Kingdom.; Einsele H; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Löffler J; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.; Wurster S; Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
Source
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
Subject
Language
English
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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Tappe, Lauruschkat, Strobel, Pantaleón García, Kurzai, Rebhan, Kraus, Pfeuffer-Jovic, Bussemer, Possler, Held, Hünniger, Kniemeyer, Schäuble, Brakhage, Panagiotou, White, Einsele, Löffler and Wurster.)
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Tappe, Lauruschkat, Strobel, Pantaleón García, Kurzai, Rebhan, Kraus, Pfeuffer-Jovic, Bussemer, Possler, Held, Hünniger, Kniemeyer, Schäuble, Brakhage, Panagiotou, White, Einsele, Löffler and Wurster.)