TY - JOUR
T1 - Infection of lung megakaryocytes and platelets by SARS-CoV-2 anticipate fatal COVID-19
AU - Zhu, Aiwei
AU - Real, Fernando
AU - Capron, Claude
AU - Rosenberg, Arielle R.
AU - Silvin, Aymeric
AU - Dunsmore, Garett
AU - Zhu, Jaja
AU - Cottoignies-Callamarte, Andréa
AU - Massé, Jean Marc
AU - Moine, Pierre
AU - Bessis, Simon
AU - Godement, Mathieu
AU - Geri, Guillaume
AU - Chiche, Jean Daniel
AU - Valdebenito, Silvana
AU - Belouzard, Sandrine
AU - Dubuisson, Jean
AU - Lorin de la Grandmaison, Geoffroy
AU - Chevret, Sylvie
AU - Ginhoux, Florent
AU - Eugenin, Eliseo A.
AU - Annane, Djillali
AU - Bordé, Elisabeth Cramer
AU - Bomsel, Morgane
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - COVID-19
KW - Lung
KW - Macrophages
KW - Megakaryocytes
KW - Platelets
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85132078452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85132078452&partnerID=8YFLogxK
U2 - 10.1007/s00018-022-04318-x
DO - 10.1007/s00018-022-04318-x
M3 - Article
C2 - 35708858
AN - SCOPUS:85132078452
SN - 1420-682X
VL - 79
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 7
M1 - 365
ER -