tetano
Editor, Senior Moderator
Cell Mol Life Sci
. 2022 Jun 16;79(7):365.
doi: 10.1007/s00018-022-04318-x.
Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19
Aiwei Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Fernando Real[SUP] #[/SUP][SUP] 1 [/SUP], Claude Capron[SUP] 2 3 [/SUP], Arielle R Rosenberg[SUP] 1 4 [/SUP], Aymeric Silvin[SUP] 5 [/SUP], Garett Dunsmore[SUP] 5 [/SUP], Jaja Zhu[SUP] 2 [/SUP], Andréa Cottoignies-Callamarte[SUP] 1 [/SUP], Jean-Marc Massé[SUP] 6 [/SUP], Pierre Moine[SUP] 7 [/SUP], Simon Bessis[SUP] 7 [/SUP], Mathieu Godement[SUP] 7 [/SUP], Guillaume Geri[SUP] 8 3 [/SUP], Jean-Daniel Chiche[SUP] 9 [/SUP], Silvana Valdebenito[SUP] 10 [/SUP], Sandrine Belouzard[SUP] 11 [/SUP], Jean Dubuisson[SUP] 11 [/SUP], Geoffroy Lorin de la Grandmaison[SUP] 12 [/SUP], Sylvie Chevret[SUP] 13 [/SUP], Florent Ginhoux[SUP] 14 15 16 [/SUP], Eliseo A Eugenin[SUP] 10 [/SUP], Djillali Annane[SUP] 7 [/SUP], Elisabeth Cramer Bordé[SUP] 3 [/SUP], Morgane Bomsel[SUP] 17 [/SUP]
Affiliations
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.
Keywords: COVID-19; Lung; Macrophages; Megakaryocytes; Platelets; SARS-CoV-2.
. 2022 Jun 16;79(7):365.
doi: 10.1007/s00018-022-04318-x.
Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19
Aiwei Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Fernando Real[SUP] #[/SUP][SUP] 1 [/SUP], Claude Capron[SUP] 2 3 [/SUP], Arielle R Rosenberg[SUP] 1 4 [/SUP], Aymeric Silvin[SUP] 5 [/SUP], Garett Dunsmore[SUP] 5 [/SUP], Jaja Zhu[SUP] 2 [/SUP], Andréa Cottoignies-Callamarte[SUP] 1 [/SUP], Jean-Marc Massé[SUP] 6 [/SUP], Pierre Moine[SUP] 7 [/SUP], Simon Bessis[SUP] 7 [/SUP], Mathieu Godement[SUP] 7 [/SUP], Guillaume Geri[SUP] 8 3 [/SUP], Jean-Daniel Chiche[SUP] 9 [/SUP], Silvana Valdebenito[SUP] 10 [/SUP], Sandrine Belouzard[SUP] 11 [/SUP], Jean Dubuisson[SUP] 11 [/SUP], Geoffroy Lorin de la Grandmaison[SUP] 12 [/SUP], Sylvie Chevret[SUP] 13 [/SUP], Florent Ginhoux[SUP] 14 15 16 [/SUP], Eliseo A Eugenin[SUP] 10 [/SUP], Djillali Annane[SUP] 7 [/SUP], Elisabeth Cramer Bordé[SUP] 3 [/SUP], Morgane Bomsel[SUP] 17 [/SUP]
Affiliations
- PMID: 35708858
- DOI: 10.1007/s00018-022-04318-x
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.
Keywords: COVID-19; Lung; Macrophages; Megakaryocytes; Platelets; SARS-CoV-2.