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Deciphering the state of immune silence in fatal COVID-19 patients

Bost P, De Sanctis F, Canè S, Ugel S, Donadello K, Castellucci M, Eyal D, Fiore A, Anselmi C, Barouni RM, Trovato R, Caligola S, Lamolinara A, Iezzi M, Facciotti F, Mazzariol A, Gibellini D, De Nardo P, Tacconelli E, Gottin L, Polati E, Schwikowski B, Amit I, Bronte V

Abstract: Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naïve lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6+ effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of 'immune silence' in patients with critical COVID-19.

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