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Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19
- Source :
- Cellular and Molecular Life Sciences, Cellular and Molecular Life Sciences, 2022, ⟨10.1007/s00018-022-04318-x⟩, Cellular and Molecular Life Sciences, 2022, 79 (7), ⟨10.1007/s00018-022-04318-x⟩
- Publication Year :
- 2022
- Publisher :
- Springer Verlag, 2022.
-
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.
Details
- Language :
- English
- ISSN :
- 1420682X and 14209071
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences, Cellular and Molecular Life Sciences, 2022, ⟨10.1007/s00018-022-04318-x⟩, Cellular and Molecular Life Sciences, 2022, 79 (7), ⟨10.1007/s00018-022-04318-x⟩
- Accession number :
- edsair.doi.dedup.....94ef83302801406e66d95c231b0dda82