Role of antibodies in platelet response to SARS-CoV-2 and its variants

Boilard, Eric | $261,700

Quebec Université Laval 2021 CIHR Operating Grant

Billions of platelets patrol blood vessels on the ready to prevent the loss of blood when a vessel is injured. The prevention of bleedings is the primarily recognized role of platelets, known since their first description in the late 19th century. When microbes such as a virus or its molecules enters the blood circulation, it generates multiple reactions such as fever, loss of blood pressure, alteration of heart rate and respiration. The virus that causes COVID‑19 firstly infects the lungs. During COVID-19, there is obstruction of blood vessels by blood clots. With their abundance in blood, platelets are chiefly positioned to interact with viruses in blood. How platelets mediate the blood vessel obstructions in COVID‑19 is however unknown. Our work has revealed that platelets are activated in COVID‑19 patients (Zaid et al. Circulation Research, 2020), which is consistent with accumulating evidence from other laboratories. Here, we will thus determine how platelets are affected by the virus. We will use very innovative technologies and compelling functional assays that we have developed to study platelets in response to the virus that causes COVID-19. We will study platelets in humans and mice, and will uncover how they can modulate the expression of inflammatory molecules in COVID- 19. Given that more and more people are immunized for the virus that causes COVID-19, we will moreover aim to understand how antibodies may either protect from, or promote, platelet activation in COVID‑19 taking in consideration emerging variants. We will thus elucidate the interplay between platelets and the virus that causes COVID-19, thereby providing new therapeutic targets, informing on potency of variants to induce thrombosis, and improving safety of vaccination.

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