Title :

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

Author(s) :

Zhu, Aiwei [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Real, Fernando [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Capron, Claude C. [Auteur]
Université de Versailles Saint-Quentin-en-Yvelines [UVSQ]
Hôpital Ambroise Paré [AP-HP]
Rosenberg, Arielle R. [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Hôpital Cochin [AP-HP]
Silvin, Aymeric [Auteur]
Immunologie anti-tumorale et immunothérapie des cancers [ITIC]
Institut Gustave Roussy [IGR]
Dunsmore, Garett [Auteur]
Immunologie anti-tumorale et immunothérapie des cancers [ITIC]
Institut Gustave Roussy [IGR]
Zhu, Jaja [Auteur]
Hôpital Ambroise Paré [AP-HP]
Cottoignies-Callamarte, Andréa [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Massé, Jean Marc [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Moine, Pierre [Auteur]
Infection et inflammation [2I]
UFR Sciences de la santé Simone Veil [UVSQ Santé]
Bessis, Simon [Auteur]
Infection et inflammation [2I]
UFR Sciences de la santé Simone Veil [UVSQ Santé]
Godement, Mathieu [Auteur]
Infection et inflammation [2I]
UFR Sciences de la santé Simone Veil [UVSQ Santé]
Geri, Guillaume [Auteur]
Université de Versailles Saint-Quentin-en-Yvelines [UVSQ]
Hôpital Ambroise Paré [AP-HP]
Chiche, Jean Daniel [Auteur]
Hôpital Cochin [AP-HP]
Valdebenito, Silvana [Auteur]
The University of Texas Medical Branch [UTMB]
Belouzard, Sandrine [Auteur]
Institut Pasteur de Lille
Dubuisson, Jèan [Auteur]
Institut Pasteur de Lille
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Lorin de la Grandmaison, Geoffroy Lorin [Auteur]
Hôpital Raymond Poincaré (Garches) [GHU AP-HP Université Paris-Saclay]
Chevret, Sylvie [Auteur]
Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) [SBIM]
Ginhoux, Florent [Auteur]
Singapore Immunology Network [SIgN]
Shanghai Jiao Tong University School of Medicine
Eugenin, Eliseo Alberto [Auteur]
The University of Texas Medical Branch [UTMB]
Annane, Djillali [Auteur]
Infection et inflammation [2I]
Hôpital Raymond Poincaré (Garches) [GHU AP-HP Université Paris-Saclay]
Bordé, Elisabeth M. [Auteur]
Université de Versailles Saint-Quentin-en-Yvelines [UVSQ]
Bomsel, Morgane [Auteur correspondant]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]

Journal title :

Cellular and Molecular Life Sciences

Publisher :

Springer Verlag

Publication date :

2022-06-16

ISSN :

1420-682X

English keyword(s) :

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

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL