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Cell Rep Med . RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity

tetano

Editor, Senior Moderator
Cell Rep Med


. 2023 Nov 6:101266.
doi: 10.1016/j.xcrm.2023.101266. Online ahead of print. RAGE engagement by SARS-CoV-2 enables monocyte infection and underlies COVID-19 severity

Roberta Angioni[SUP] 1 [/SUP], Matteo Bonfanti[SUP] 2 [/SUP], Nicolò Caporale[SUP] 3 [/SUP], Ricardo Sánchez-Rodríguez[SUP] 1 [/SUP], Fabio Munari[SUP] 1 [/SUP], Aurora Savino[SUP] 2 [/SUP], Sebastiano Pasqualato[SUP] 2 [/SUP], Damiano Buratto[SUP] 4 [/SUP], Isabel Pagani[SUP] 5 [/SUP], Nicole Bertoldi[SUP] 1 [/SUP], Carlo Zanon[SUP] 6 [/SUP], Paolo Ferrari[SUP] 2 [/SUP], Eugenia Ricciardelli[SUP] 2 [/SUP], Cristina Putaggio[SUP] 7 [/SUP], Silvia Ghezzi[SUP] 5 [/SUP], Francesco Elli[SUP] 8 [/SUP], Luca Rotta[SUP] 9 [/SUP], Alessandro Scardua[SUP] 2 [/SUP], Janine Weber[SUP] 2 [/SUP], Valentina Cecatiello[SUP] 2 [/SUP], Francesco Iorio[SUP] 2 [/SUP], Francesco Zonta[SUP] 10 [/SUP], Anna Maria Cattelan[SUP] 7 [/SUP], Elisa Vicenzi[SUP] 5 [/SUP], Alessandro Vannini[SUP] 2 [/SUP], Barbara Molon[SUP] 1 [/SUP], Carlo Emanuele Villa[SUP] 11 [/SUP], Antonella Viola[SUP] 12 [/SUP], Giuseppe Testa[SUP] 13 [/SUP]



Affiliations
Abstract

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges because of subsequent waves and long-term consequences of great concern. Here, we chart the molecular basis of COVID-19 pathogenesis by analyzing patients' immune responses at single-cell resolution across disease course and severity. This approach confirms cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identifies a severity-associated activation of the receptor for advanced glycation endproducts (RAGE) pathway in monocytes. In vitro THP1-based experiments indicate that monocytes bind the SARS-CoV-2 S1-receptor binding domain (RBD) via RAGE, pointing to RAGE-Spike interaction enabling monocyte infection. Thus, our results demonstrate that RAGE is a functional receptor of SARS-CoV-2 contributing to COVID-19 severity.


 
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