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

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.

• Authors: 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 Ginhoux, Eliseo A Eugenin, Djillali Annane, Elisabeth Cramer Bordé, Morgane Bomsel
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 79 Issue 7 Pg. 365 (Jun 16 2022) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 35708858 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• IFITM3 protein, human
• Membrane Proteins
• RNA-Binding Proteins

Topics

• Blood Platelets
• COVID-19
• Humans
• Lung
• Megakaryocytes
• Membrane Proteins
• RNA-Binding Proteins
• SARS-CoV-2
• Thrombosis