COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
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..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 13(2022) vom: 16., Seite 954985 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tappe, Beeke [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Adrenal Cortex Hormones |
|---|
| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 15.09.2022 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2022.954985 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM345693612 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM345693612 | ||
| 003 | DE-627 | ||
| 005 | 20231226205219.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2022.954985 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1152.xml |
| 035 | |a (DE-627)NLM345693612 | ||
| 035 | |a (NLM)36052094 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tappe, Beeke |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.09.2022 | ||
| 500 | |a Date Revised 15.09.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Aspergillus | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Rhizopus | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a granulocytes | |
| 650 | 4 | |a immune impairment | |
| 650 | 7 | |a Adrenal Cortex Hormones |2 NLM | |
| 650 | 7 | |a Cytokines |2 NLM | |
| 700 | 1 | |a Lauruschkat, Chris D |e verfasserin |4 aut | |
| 700 | 1 | |a Strobel, Lea |e verfasserin |4 aut | |
| 700 | 1 | |a Pantaleón García, Jezreel |e verfasserin |4 aut | |
| 700 | 1 | |a Kurzai, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Rebhan, Silke |e verfasserin |4 aut | |
| 700 | 1 | |a Kraus, Sabrina |e verfasserin |4 aut | |
| 700 | 1 | |a Pfeuffer-Jovic, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Bussemer, Lydia |e verfasserin |4 aut | |
| 700 | 1 | |a Possler, Lotte |e verfasserin |4 aut | |
| 700 | 1 | |a Held, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Hünniger, Kerstin |e verfasserin |4 aut | |
| 700 | 1 | |a Kniemeyer, Olaf |e verfasserin |4 aut | |
| 700 | 1 | |a Schäuble, Sascha |e verfasserin |4 aut | |
| 700 | 1 | |a Brakhage, Axel A |e verfasserin |4 aut | |
| 700 | 1 | |a Panagiotou, Gianni |e verfasserin |4 aut | |
| 700 | 1 | |a White, P Lewis |e verfasserin |4 aut | |
| 700 | 1 | |a Einsele, Hermann |e verfasserin |4 aut | |
| 700 | 1 | |a Löffler, Jürgen |e verfasserin |4 aut | |
| 700 | 1 | |a Wurster, Sebastian |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 13(2022) vom: 16., Seite 954985 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2022 |g day:16 |g pages:954985 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2022.954985 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2022 |b 16 |h 954985 | ||