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Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery
Steven Tiwen Chen; Matthew D Park; Diane Marie Del Valle; Mark Buckup; Alexandra Tabachnikova; Nicole W Simons; Konstantinos Mouskas; Brian Lee; Daniel Geanon; Travis Dawson; Robert Marvin; Kai Nie; Ryan Thompson; Zhen Zhao; Jessica LeBerichel; Christie Chang; Hajra Jamal; Udit Chaddha; Kusum Mathews; Samuel Acquah; Stacey-Ann Brown; Michelle Reiss; Timothy Harkin; Marc Feldmann; Charles A Powell; Jaime Hook; Seunghee Kim-Schulze; Adeeb H Rahman; Brian Brown; - The COVID-19 Biobank Team; Noam D Beckmann; Sacha Gnjatic; Ephraim Kenigsberg; Alexander Charney; Miriam Merad.
Afiliación
  • Steven Tiwen Chen; Icahn School of Medicine at Mount Sinai
  • Matthew D Park; Icahn School of Medicine at Mount Sinai
  • Diane Marie Del Valle; Icahn School of Medicine at Mount Sinai
  • Mark Buckup; Icahn School of Medicine at Mount Sinai
  • Alexandra Tabachnikova; Icahn School of Medicine at Mount Sinai
  • Nicole W Simons; Icahn School of Medicine at Mount Sinai
  • Konstantinos Mouskas; Icahn School of Medicine at Mount Sinai
  • Brian Lee; Icahn School of Medicine at Mount Sinai
  • Daniel Geanon; Icahn School of Medicine at Mount Sinai
  • Travis Dawson; Icahn School of Medicine at Mount Sinai
  • Robert Marvin; Icahn School of Medicine at Mount Sinai
  • Kai Nie; Icahn School of Medicine at Mount Sinai
  • Ryan Thompson; Icahn School of Medicine at Mount Sinai
  • Zhen Zhao; Icahn School of Medicine at Mount Sinai
  • Jessica LeBerichel; Icahn School of Medicine at Mount Sinai
  • Christie Chang; Icahn School of Medicine at Mount Sinai
  • Hajra Jamal; Icahn School of Medicine at Mount Sinai
  • Udit Chaddha; Icahn School of Medicine at Mount Sinai
  • Kusum Mathews; Icahn School of Medicine at Mount Sinai
  • Samuel Acquah; Icahn School of Medicine at Mount Sinai
  • Stacey-Ann Brown; Icahn School of Medicine at Mount Sinai
  • Michelle Reiss; Icahn School of Medicine at Mount Sinai
  • Timothy Harkin; Icahn School of Medicine at Mount Sinai
  • Marc Feldmann; University of Oxford
  • Charles A Powell; Icahn School of Medicine at Mount Sinai
  • Jaime Hook; Icahn School of Medicine at Mount Sinai
  • Seunghee Kim-Schulze; Icahn School of Medicine at Mount Sinai
  • Adeeb H Rahman; Icahn School of Medicine at Mount Sinai
  • Brian Brown; Icahn School of Medicine at Mount Sinai
  • - The COVID-19 Biobank Team; -
  • Noam D Beckmann; Icahn School of Medicine at Mount Sinai
  • Sacha Gnjatic; Icahn School of Medicine at Mount Sinai
  • Ephraim Kenigsberg; Icahn School of Medicine at Mount Sinai
  • Alexander Charney; Icahn School of Medicine at Mount Sinai
  • Miriam Merad; Icahn School of Medicine at Mount Sinai
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-475918
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 (MoM{Phi}). 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.
Licencia
cc_by_nc
Texto completo: Disponible Colección: Preprints Base de datos: bioRxiv Tipo de estudio: Estudio pronóstico Idioma: Inglés Año: 2022 Tipo del documento: Preprint
Texto completo: Disponible Colección: Preprints Base de datos: bioRxiv Tipo de estudio: Estudio pronóstico Idioma: Inglés Año: 2022 Tipo del documento: Preprint
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