Whole blood assays demonstrate reduced platelet function in early SARS-CoV-2 infection

Background : Patients with COVID-19 frequently present with hypercoagulability. It has been shown that an increased reactivity of platelets might contribute to this prothrombotic disposition. However, previous studies were mostly performed with purified platelets and focused on severe COVID-19 patients. Aims : To assess platelet function in early SARS-CoV-2 infection using whole blood assays. Methods : We performed whole blood impedance aggregometry in 20 SARS-CoV-2 positive patients and 58 SARS-CoV-2 negative patients from an all-comers cohort presenting with suspected or confirmed COVID-19 at our emergency department. 15 healthy volunteers were included as controls. Thrombin receptor activating peptide 6 (TRAP-6), adenosine diphosphate (ADP) and arachidonic acid (AA) were used as agonists. In a subset of SARS-CoV-2 positive patients ( n = 14), SARS-CoV-2 negative patients ( n = 7) and healthy controls ( n = 7), we investigated the expression of typical surface platelet activation markers (P-selectin, active GPIIb/IIIa) using flow cytometry. One-way ANOVA and Bonferroni's multiple comparisons test were used for statistical analyses. The study complies with the Declaration of Helsinki and was approved by the ethical committee of the University of Freiburg. Written informed consent was obtained from all participants. Results : Surprisingly, platelet aggregation was significantly reduced in SARS-CoV-2 positive patients in response to all agonists tested compared to SARS-CoV-2 negative patients (TRAP: P < 0.01;ADP: P < 0.05;AA: P < 0.01). The difference was even more pronounced when comparing with healthy controls (TRAP: P < 0.0001;ADP: P < 0.001;AA: P < 0.001). P-selectin surface expression was not different between groups. However, GPIIb/IIIa activation was decreased in SARS-CoV-2 positive patients compared to healthy controls (TRAP: P < 0.01;ADP: P < 0.05). Conclusions : In contrast to previous findings, our study revealed decreased platelet reactivity in patients with COVID-19. This discrepancy could be due to the use of different methodological approaches for testing platelet function and different severity levels of COVID-19 patients. We conclude that anti-platelet medication is not required in early SARS-CoV-2 infection.