COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
Abstract Patients suffering from coronavirus disease-2019 (COVID-19) are at high risk for deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM). 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 anex-vivowhole blood (WB) stimulation assay, we challenged blood from twelve COVID-19 patients withAspergillus fumigatusandRhizopus arrhizusantigens 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 weakenedA. fumigatus- andR. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, WB 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 toA. fumigatusandR. arrhizusantigens. 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..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 05. Feb. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Tappe, Beeke [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2022.04.21.22274082 |
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funding: |
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PPN (Katalog-ID): |
XBI036024333 |
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520 | |a Abstract Patients suffering from coronavirus disease-2019 (COVID-19) are at high risk for deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM). 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 anex-vivowhole blood (WB) stimulation assay, we challenged blood from twelve COVID-19 patients withAspergillus fumigatusandRhizopus arrhizusantigens 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 weakenedA. fumigatus- andR. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, WB 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 toA. fumigatusandR. arrhizusantigens. 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. | ||
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