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Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery.
Chen, Steven T; Park, Matthew D; Del Valle, Diane Marie; Buckup, Mark; Tabachnikova, Alexandra; Simons, Nicole W; Mouskas, Konstantinos; Lee, Brian; Geanon, Daniel; D'Souza, Darwin; Dawson, Travis; Marvin, Robert; Nie, Kai; Thompson, Ryan C; Zhao, Zhen; LeBerichel, Jessica; Chang, Christie; Jamal, Hajra; Chaddha, Udit; Mathews, Kusum; Acquah, Samuel; Brown, Stacey-Ann; Reiss, Michelle; Harkin, Timothy; Feldmann, Marc; Powell, Charles A; Hook, Jaime L; Kim-Schulze, Seunghee; Rahman, Adeeb H; Brown, Brian D; Beckmann, Noam D; Gnjatic, Sacha; Kenigsberg, Ephraim; Charney, Alexander W; Merad, Miriam.
Affiliation
  • Chen ST; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Park MD; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Del Valle DM; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Buckup M; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Tabachnikova A; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Simons NW; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Mouskas K; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Lee B; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Geanon D; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • D'Souza D; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Dawson T; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Marvin R; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Nie K; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Thompson RC; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Zhao Z; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • LeBerichel J; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Chang C; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Jamal H; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Chaddha U; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Mathews K; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Acquah S; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Brown SA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Reiss M; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Harkin T; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Feldmann M; Icahn Institute of Data Science and Genomics Technology, New York, NY, 10029, USA.
  • Powell CA; Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Hook JL; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Kim-Schulze S; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Rahman AH; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Brown BD; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Beckmann ND; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Gnjatic S; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Kenigsberg E; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Charney AW; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
  • Merad M; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
bioRxiv ; 2022 Jan 12.
Article in En | MEDLINE | ID: mdl-35043110
ABSTRACT
Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative therapies to treat COVID-19 and other inflammatory diseases which remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and death to develop tailored immunotherapy strategies to halt disease progression. Here we assembled the Mount Sinai COVID-19 Biobank which was comprised of ~600 hospitalized patients followed longitudinally during the peak of the pandemic. Moderate disease and survival were associated with a stronger antigen (Ag) presentation and effector T cell signature, while severe disease and death were associated with an altered Ag presentation signature, increased numbers of circulating inflammatory, immature myeloid cells, and extrafollicular activated B cells associated with autoantibody formation. Strikingly, we found that in severe COVID-19 patients, lung tissue resident alveolar macrophages (AM) were not only severely depleted, but also had an altered Ag presentation signature, and were replaced by inflammatory monocytes and monocyte-derived macrophages (MoMΦ). Notably, the size of the AM pool correlated with recovery or death, while AM loss and functionality were restored in patients that recovered. These data therefore suggest that local and systemic myeloid cell dysregulation is a driver of COVID-19 severity and that modulation of AM numbers and functionality in the lung may be a viable therapeutic strategy for the treatment of critical lung inflammatory illnesses.

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: BioRxiv Year: 2022 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: BioRxiv Year: 2022 Document type: Article Affiliation country: