Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19 - Institut Gustave Roussy Accéder directement au contenu
Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2022

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

Aiwei Zhu
  • Fonction : Auteur
Fernando Real
  • Fonction : Auteur
Jean Marc Massé
  • Fonction : Auteur
Morgane Bomsel

Résumé

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.
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hal-03775756 , version 1 (06-06-2023)

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Aiwei Zhu, Fernando Real, Claude C. Capron, Arielle R. Rosenberg, Aymeric Silvin, et al.. Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19. Cellular and Molecular Life Sciences, 2022, 79 (7), ⟨10.1007/s00018-022-04318-x⟩. ⟨hal-03775756⟩
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