SARS-CoV-2 Receptors are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients

Abstract

Coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of anti-platelet agents in attenuating thrombosis is unknown. We aimed to determine if human platelets express the known SARS-CoV-2 receptor-protease axis on their cell surface and assess whether the anti-platelet effect of aspirin may mitigate risk of myocardial infarction (MI), cerebrovascular accident (CVA), and venous thromboembolism (VTE) in COVID-19. Expression of ACE2 and TMPRSS2 on human platelets were detected by immunoblotting and confirmed by confocal microscopy. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. However, both aspirin and NSAID therapies were associated with increased risk of the combined thrombotic endpoint of (MI), (CVA), and (VTE). Thus, while platelets clearly express ACE2-TMPRSS2 receptor-protease axis for SARS-CoV-2 infection, aspirin does not prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appears distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

Pericardial Diseases in COVID19: a Contemporary Review

“…Observational studies on the use of aspirin in COVID19 patients have shown conflicting results. Chow et al [76] reported decreased mortality, ICU admission, and mechanical ventilation, but Sahai et al [77] found no change in mortality and an increased thrombotic risk in COVID19 patients taking aspirin. Current World Health Organization and Food and Drug Administration guidelines do not recommend stopping NSAIDs in symptomatic COVID19 patients [78,79].…”

Pleiotropic Effects of Acetylsalicylic Acid after Coronary Artery Bypass Grafting—Beyond Platelet Inhibition

“…Accumulating data prove the relationship between COVID-19 and thrombosis [ 84 ]. The clinical and autopsy studies indicate that the risks of microvascular thrombosis, venous thromboembolism, and ischemic stroke are higher in COVID-19 patients [ 85 , 86 ]. Also, it was found that platelets have high affinity receptors for SARS-CoV-2, suggesting that platelets may participate in the development of COVID-19 [ 85 ].…”

“…The clinical and autopsy studies indicate that the risks of microvascular thrombosis, venous thromboembolism, and ischemic stroke are higher in COVID-19 patients [ 85 , 86 ]. Also, it was found that platelets have high affinity receptors for SARS-CoV-2, suggesting that platelets may participate in the development of COVID-19 [ 85 ]. Thus, the application of antiplatelet drugs in the prophylaxis and treatment of COVID-19 and related complications might be a viable treatment strategy.…”

Application of an evidence-based, out-patient treatment strategy for COVID-19: Multidisciplinary medical practice principles to prevent severe disease

“…Unless formal anticoagulation is indicated, (per guidelines contingent upon D-Dimer levels), we recommend 1 baby aspirin daily (81 mg) for purposes of reducing clot and sludging via platelet inhibition (unless aspirin in the patient is contraindicated). [68][69][70][71][72][73][74][75][76][77]…”