tetano
Editor, Senior Moderator
Nat Med
. 2021 Nov 15.
doi: 10.1038/s41591-021-01576-3. Online ahead of print.
Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19
Sarthak Sinha[SUP] #[/SUP][SUP] 1 [/SUP], Nicole L Rosin[SUP] #[/SUP][SUP] 2 [/SUP], Rohit Arora[SUP] 1 [/SUP], Elodie Labit[SUP] 1 [/SUP], Arzina Jaffer[SUP] 1 [/SUP], Leslie Cao[SUP] 1 [/SUP], Raquel Farias[SUP] 3 4 [/SUP], Angela P Nguyen[SUP] 3 4 [/SUP], Luiz G N de Almeida[SUP] 5 6 [/SUP], Antoine Dufour[SUP] 5 6 [/SUP], Amy Bromley[SUP] 7 [/SUP], Braedon McDonald[SUP] 3 4 [/SUP], Mark R Gillrie[SUP] 3 8 9 [/SUP], Marvin J Fritzler[SUP] 3 9 [/SUP], Bryan G Yipp[SUP] 10 11 [/SUP], Jeff Biernaskie[SUP] 12 13 14 15 [/SUP]
Affiliations
Abstract
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN[SUP]active[/SUP] neutrophils, downregulated interferon-stimulated genes and activated IL-1R2[SUP]+[/SUP] neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN[SUP]active[/SUP] neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
. 2021 Nov 15.
doi: 10.1038/s41591-021-01576-3. Online ahead of print.
Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19
Sarthak Sinha[SUP] #[/SUP][SUP] 1 [/SUP], Nicole L Rosin[SUP] #[/SUP][SUP] 2 [/SUP], Rohit Arora[SUP] 1 [/SUP], Elodie Labit[SUP] 1 [/SUP], Arzina Jaffer[SUP] 1 [/SUP], Leslie Cao[SUP] 1 [/SUP], Raquel Farias[SUP] 3 4 [/SUP], Angela P Nguyen[SUP] 3 4 [/SUP], Luiz G N de Almeida[SUP] 5 6 [/SUP], Antoine Dufour[SUP] 5 6 [/SUP], Amy Bromley[SUP] 7 [/SUP], Braedon McDonald[SUP] 3 4 [/SUP], Mark R Gillrie[SUP] 3 8 9 [/SUP], Marvin J Fritzler[SUP] 3 9 [/SUP], Bryan G Yipp[SUP] 10 11 [/SUP], Jeff Biernaskie[SUP] 12 13 14 15 [/SUP]
Affiliations
- PMID: 34782790
- DOI: 10.1038/s41591-021-01576-3
Abstract
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN[SUP]active[/SUP] neutrophils, downregulated interferon-stimulated genes and activated IL-1R2[SUP]+[/SUP] neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN[SUP]active[/SUP] neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.