Platelets can contain SARS-CoV-2 RNA and are hyperactivated in COVID-19

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: We document the presence of SARS-CoV-2 RNA in platelets of COVID-19 patients. Exhaustive assessment of cytokines in plasma and in platelets revealed the modulation of platelet-associated cytokine levels in COVID-19, pointing to a direct contribution of platelets to the plasmatic cytokine load. Moreover, we demonstrate that platelets release their alpha- and dense-granule contents and phosphatidylserine-exposing extracellular vesicles. Functionally, platelets were hyperactivated in COVID-19 subjects, with aggregation occurring at suboptimal thrombin concentrations. Furthermore, platelets adhered more efficiently onto collagen-coated surfaces under flow conditions. Conclusions: These data suggest that platelets could participate in the dissemination of SARS-CoV-2 and in the overwhelming thrombo-inflammation observed in COVID-19. Thus, blockade of platelet activation pathways may improve outcomes in this disease.

SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19

“…Actually, the COVID-19 virus can induce ACE2 internalization and subsequent degradation, evidenced by our study of SARS-CoV-2-induced ACE2 degradation in platelets (Additional file 1: Online Figure 5) and the other studies on SARS-CoV-2-induced ACE2 degradation [30]. Moreover, a recent study indicated that SARS-CoV-2 infection could downregulate ACE2 at the mRNA level and this effect requires action directly on the ACE2 promoter [71]. In consistent with the identification of platelet ACE2 in our results, Zaid et al also found that ACE2 mRNA was presented in platelets from both healthy people and COVID-19 patients [72].…”

Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction

“…Indeed, this hypothesis is supported by pre-publication evidence reporting the presence of SARS-CoV-2 RNA in platelets of COVID-19 patients, which were shown to be hyperactivated and aggregated at a lower threshold of in vitro thrombin stimulation (125). Platelets from COVID-19 degranulate, which correlates with reduced platelet factor 4 and serotonin levels, and release extracellular vesicles to participate in coagulation (125). Consequently, platelet reprogramming could facilitate the transmission of SARS-CoV-2 and promote thrombo-inflammation.…”

“…Platelets from COVID-19 patients induces ex vivo expression of tissue factor (TF) in monocytes (124), indicating a likely reprogramming event during SARS-CoV-2 infection. Indeed, this hypothesis is supported by pre-publication evidence reporting the presence of SARS-CoV-2 RNA in platelets of COVID-19 patients, which were shown to be hyperactivated and aggregated at a lower threshold of in vitro thrombin stimulation (125). Platelets from COVID-19 degranulate, which correlates with reduced platelet factor 4 and serotonin levels, and release extracellular vesicles to participate in coagulation (125).…”

Is there a role for the ACE2 receptor in SARS‐CoV‐2 interactions with platelets?

“…Recently, several independent studies have demonstrated that platelets are activated in COVID‐19 patients 9‐14 . Platelets from COVID‐19 patients are hyperreactive in comparison to healthy donors when activated with traditional platelet agonists such as adenosine diphospate, collagen, and thrombin.…”