Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19

Zhu, Aiwei; Real, Fernando; Capron, Claude; Rosenberg, Arielle R.; Silvin, Aymeric; Dunsmore, Garett; Zhu, Jaja; Cottoignies-Callamarte, Andrea; Masse, Jean-Marc; Moine, Pierre; Bessis, Simon; Godement, Mathieu; Geri, Guillaume; Chiche, Jean-Daniel; Valdebenito, Silvana; et. al.

Abstract

SARS-CoV-2, although not being a circulatory virus, spread from the respiratory tract resulting in multiorgan failures and thrombotic complications, the hallmarks of fatal COVID-19. A convergent contributor could be platelets that beyond hemostatic functions can carry infectious viruses. Here, we profiled 52 patients with severe COVID-19 and demonstrated that circulating platelets of 19 out 20 non-survivor patients contain SARS-CoV-2 in robust correlation with fatal outcome. Platelets containing SARS-CoV-2 might originate from bone marrow and lung megakaryocytes (MKs), the platelet precursors, which were found infected by SARS-CoV-2 in COVID-19 autopsies. Accordingly, MKs undergoing shortened differentiation and expressing anti-viral IFITM1 and IFITM3 RNA as a sign of viral sensing were enriched in the circulation of deadly COVID-19. Infected MKs reach the lung concomitant with a specific MK-related cytokine storm rich in VEGF, PDGF and inflammatory molecules, anticipating fatal outcome. Lung macrophages capture SARS-CoV-2-containing platelets in vivo. The virus contained by platelets is infectious as capture of platelets carrying SARS-CoV-2 propagates infection to macrophages in vitro, in a process blocked by an anti-GPIIbIIIa drug. Altogether, platelets containing infectious SARS-CoV-2 alter COVID-19 pathogenesis and provide a powerful fatality marker. Clinical targeting of platelets might prevent viral spread, thrombus formation and exacerbated inflammation at once and increase survival in COVID-19.

Más información

Título según WOS: ID WOS:000812256600001 Not found in local WOS DB
Título de la Revista: CELLULAR AND MOLECULAR LIFE SCIENCES
Volumen: 79
Número: 7
Editorial: SPRINGER BASEL AG
Fecha de publicación: 2022
DOI:

10.1007/s00018-022-04318-x

Notas: ISI