TY - JOUR
T1 - COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
AU - Tappe, Beeke
AU - Lauruschkat, Chris D.
AU - Strobel, Lea
AU - Pantaleón García, Jezreel
AU - Kurzai, Oliver
AU - Rebhan, Silke
AU - Kraus, Sabrina
AU - Pfeuffer-Jovic, Elena
AU - Bussemer, Lydia
AU - Possler, Lotte
AU - Held, Matthias
AU - Hünniger, Kerstin
AU - Kniemeyer, Olaf
AU - Schäuble, Sascha
AU - Brakhage, Axel A.
AU - Panagiotou, Gianni
AU - White, P. Lewis
AU - Einsele, Hermann
AU - Löffler, Jürgen
AU - Wurster, Sebastian
N1 - Publisher Copyright:
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.
PY - 2022/8/16
Y1 - 2022/8/16
N2 - 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.
AB - 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.
KW - Aspergillus
KW - COVID-19
KW - granulocytes
KW - immune impairment
KW - Rhizopus
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=85137085355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85137085355&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.954985
DO - 10.3389/fimmu.2022.954985
M3 - Article
C2 - 36052094
AN - SCOPUS:85137085355
SN - 1664-3224
VL - 13
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 954985
ER -