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

Aiwei Zhu, Fernando Real, Claude Capron, Arielle R. Rosenberg, Aymeric Silvin, Garett Dunsmore, Jaja Zhu, Andréa Cottoignies-Callamarte, Jean Marc Massé, Pierre Moine, Simon Bessis, Mathieu Godement, Guillaume Geri, Jean Daniel Chiche, Silvana Valdebenito, Sandrine Belouzard, Jean Dubuisson, Geoffroy Lorin de la Grandmaison, Sylvie Chevret, Florent GinhouxEliseo A. Eugenin, Djillali Annane, Elisabeth Cramer Bordé, Morgane Bomsel

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Article number365
JournalCellular and Molecular Life Sciences
Volume79
Issue number7
DOIs
StatePublished - Jul 2022
Externally publishedYes

Keywords

  • COVID-19
  • Lung
  • Macrophages
  • Megakaryocytes
  • Platelets
  • SARS-CoV-2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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