tetano
Editor, Senior Moderator
Front Immunol
. 2022 Aug 16;13:954985.
doi: 10.3389/fimmu.2022.954985. eCollection 2022.
COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
Beeke Tappe[SUP] 1 [/SUP], Chris D Lauruschkat[SUP] 1 [/SUP], Lea Strobel[SUP] 1 [/SUP], Jezreel Pantaleón García[SUP] 2 [/SUP], Oliver Kurzai[SUP] 3 4 [/SUP], Silke Rebhan[SUP] 1 [/SUP], Sabrina Kraus[SUP] 1 [/SUP], Elena Pfeuffer-Jovic[SUP] 5 [/SUP], Lydia Bussemer[SUP] 1 [/SUP], Lotte Possler[SUP] 6 [/SUP], Matthias Held[SUP] 5 [/SUP], Kerstin Hünniger[SUP] 3 4 [/SUP], Olaf Kniemeyer[SUP] 4 [/SUP], Sascha Schäuble[SUP] 4 [/SUP], Axel A Brakhage[SUP] 4 7 [/SUP], Gianni Panagiotou[SUP] 4 [/SUP], P Lewis White[SUP] 8 [/SUP], Hermann Einsele[SUP] 1 [/SUP], Jürgen Löffler[SUP] 1 [/SUP], Sebastian Wurster[SUP] 9 [/SUP]
Affiliations
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.
Keywords: Aspergillus; COVID-19; Rhizopus; T cells; granulocytes; immune impairment.
. 2022 Aug 16;13:954985.
doi: 10.3389/fimmu.2022.954985. eCollection 2022.
COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
Beeke Tappe[SUP] 1 [/SUP], Chris D Lauruschkat[SUP] 1 [/SUP], Lea Strobel[SUP] 1 [/SUP], Jezreel Pantaleón García[SUP] 2 [/SUP], Oliver Kurzai[SUP] 3 4 [/SUP], Silke Rebhan[SUP] 1 [/SUP], Sabrina Kraus[SUP] 1 [/SUP], Elena Pfeuffer-Jovic[SUP] 5 [/SUP], Lydia Bussemer[SUP] 1 [/SUP], Lotte Possler[SUP] 6 [/SUP], Matthias Held[SUP] 5 [/SUP], Kerstin Hünniger[SUP] 3 4 [/SUP], Olaf Kniemeyer[SUP] 4 [/SUP], Sascha Schäuble[SUP] 4 [/SUP], Axel A Brakhage[SUP] 4 7 [/SUP], Gianni Panagiotou[SUP] 4 [/SUP], P Lewis White[SUP] 8 [/SUP], Hermann Einsele[SUP] 1 [/SUP], Jürgen Löffler[SUP] 1 [/SUP], Sebastian Wurster[SUP] 9 [/SUP]
Affiliations
- PMID: 36052094
- PMCID: PMC9427195
- 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.
Keywords: Aspergillus; COVID-19; Rhizopus; T cells; granulocytes; immune impairment.