The spatial landscape of lung pathology during COVID-19 progression

André F. Rendeiro, Hiranmayi Ravichandran, Yaron Bram, Vasuretha Chandar, Junbum Kim, Cem Meydan, Jiwoon Park, Jonathan Foox, Tyler Hether, Sarah Warren, Youngmi Kim, Jason Reeves, Steven Salvatore, Christopher E. Mason, Eric C. Swanson, Alain C. Borczuk (), Olivier Elemento () and Robert E. Schwartz ()
Additional contact information
André F. Rendeiro: Weill Cornell Medicine
Hiranmayi Ravichandran: Weill Cornell Medicine
Yaron Bram: Weill Cornell Medicine
Vasuretha Chandar: Weill Cornell Medicine
Junbum Kim: Weill Cornell Medicine
Cem Meydan: Weill Cornell Medicine
Jiwoon Park: Weill Cornell Medicine
Jonathan Foox: Weill Cornell Medicine
Tyler Hether: NanoString Technologies, Inc
Sarah Warren: NanoString Technologies, Inc
Youngmi Kim: NanoString Technologies, Inc
Jason Reeves: NanoString Technologies, Inc
Steven Salvatore: Weill Cornell Medicine
Christopher E. Mason: Weill Cornell Medicine
Eric C. Swanson: Fluidigm Inc., Markham
Alain C. Borczuk: Weill Cornell Medicine
Olivier Elemento: Weill Cornell Medicine
Robert E. Schwartz: Weill Cornell Medicine

Nature, 2021, vol. 593, issue 7860, 564-569

Abstract: Abstract Recent studies have provided insights into the pathology of and immune response to COVID-191–8. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry9 that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution. These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage. We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue. Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general.

Date: 2021
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DOI: 10.1038/s41586-021-03475-6

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