tetano
Editor, Senior Moderator
Circ Res
. 2020 Sep 17.
doi: 10.1161/CIRCRESAHA.120.317703. Online ahead of print.
Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19
Younes Zaid[SUP] 1 [/SUP], Florian Puhm[SUP] 2 [/SUP], Isabelle Allaeys[SUP] 3 [/SUP], Abdallah Naya[SUP] 4 [/SUP], Mounia Oudghiri[SUP] 4 [/SUP], Loubna Khalki[SUP] 5 [/SUP], Youness Limami[SUP] 1 [/SUP], Nabil Zaid[SUP] 6 [/SUP], Khalid Sadki[SUP] 7 [/SUP], Rafiqua Ben El Haj[SUP] 8 [/SUP], Wissal Mahir[SUP] 8 [/SUP], Lamiae Belayachi[SUP] 8 [/SUP], Bouchra Belefquih[SUP] 8 [/SUP], Amina Benouda[SUP] 8 [/SUP], Amine Cheikh[SUP] 9 [/SUP], Marc-Andr? Langlois[SUP] 10 [/SUP], Yahia Cherrah[SUP] 8 [/SUP], Louis Flamand[SUP] 2 [/SUP], Fadila Guessous[SUP] 11 [/SUP], Eric Boilard[SUP] 12 [/SUP]
Affiliations
Abstract
Rationale: In addition to the overwhelming lung inflammation that prevails in COVID-19, hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19. Objective: To evaluate the contribution of platelets to inflammation and thrombosis in COVID-19 patients. Methods and Results: Blood was collected from 115 consecutive COVID-19 patients presenting non-severe (n=71) and severe (n=44) respiratory symptoms. We document the presence of SARS-CoV-2 RNA associated with platelets of COVID-19 patients. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both non-severe and severe COVID-19 patients, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both non-severe and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in non-severe, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting non-severe and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Conclusions: Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.
Keywords: SARS-CoV-2.
. 2020 Sep 17.
doi: 10.1161/CIRCRESAHA.120.317703. Online ahead of print.
Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19
Younes Zaid[SUP] 1 [/SUP], Florian Puhm[SUP] 2 [/SUP], Isabelle Allaeys[SUP] 3 [/SUP], Abdallah Naya[SUP] 4 [/SUP], Mounia Oudghiri[SUP] 4 [/SUP], Loubna Khalki[SUP] 5 [/SUP], Youness Limami[SUP] 1 [/SUP], Nabil Zaid[SUP] 6 [/SUP], Khalid Sadki[SUP] 7 [/SUP], Rafiqua Ben El Haj[SUP] 8 [/SUP], Wissal Mahir[SUP] 8 [/SUP], Lamiae Belayachi[SUP] 8 [/SUP], Bouchra Belefquih[SUP] 8 [/SUP], Amina Benouda[SUP] 8 [/SUP], Amine Cheikh[SUP] 9 [/SUP], Marc-Andr? Langlois[SUP] 10 [/SUP], Yahia Cherrah[SUP] 8 [/SUP], Louis Flamand[SUP] 2 [/SUP], Fadila Guessous[SUP] 11 [/SUP], Eric Boilard[SUP] 12 [/SUP]
Affiliations
- PMID: 32938299
- DOI: 10.1161/CIRCRESAHA.120.317703
Abstract
Rationale: In addition to the overwhelming lung inflammation that prevails in COVID-19, hypercoagulation and thrombosis contribute to the lethality of subjects infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Platelets are chiefly implicated in thrombosis. Moreover, they can interact with viruses and are an important source of inflammatory mediators. While a lower platelet count is associated with severity and mortality, little is known about platelet function during COVID-19. Objective: To evaluate the contribution of platelets to inflammation and thrombosis in COVID-19 patients. Methods and Results: Blood was collected from 115 consecutive COVID-19 patients presenting non-severe (n=71) and severe (n=44) respiratory symptoms. We document the presence of SARS-CoV-2 RNA associated with platelets of COVID-19 patients. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in both non-severe and severe COVID-19 patients, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents in both non-severe and severe forms of COVID-19. In comparison to concentrations measured in healthy volunteers, phosphatidylserine-exposing platelet extracellular vesicles were increased in non-severe, but not in severe cases of COVID-19. Levels of D-dimers, a marker of thrombosis, failed to correlate with any measured indicators of platelet activation. Functionally, platelets were hyperactivated in COVID-19 subjects presenting non-severe and severe symptoms, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Conclusions: Taken together, the data suggest that platelets are at the frontline of COVID-19 pathogenesis, as they release various sets of molecules through the different stages of the disease. Platelets may thus have the potential to contribute to the overwhelming thrombo-inflammation in COVID-19, and the inhibition of pathways related to platelet activation may improve the outcomes during COVID-19.
Keywords: SARS-CoV-2.