Anticoagulant protein S in COVID-19: low activity, and associated with outcome

Introduction. COVID-19 disease was associated with both thrombo-embolic events and in-situ thrombi formation in small vessels. Antiphospholipidic antibodies were found in some studies. Aim. Assessment of protein S activity in patients with COVID-19 as a cause of this prothrombotic state, and of the association of protein S activity with worse outcome. Methods. All patients admitted for COVID-19 disease in a university hospital between 15th of May and 15th of July 2020 were prospectively enrolled into this cohort study. Patients treated with antivitamin K anticoagulants and with liver disease were excluded. All patients had protein S activity determined at admission. The main outcome was survival, while secondary outcomes were clinical severity and lung damage. Results. 91 patients were included, of which 21 (23.3%) died. Protein S activity was decreased in 65% of the patients. Death was associated with lower activity of protein S (median 42% vs. 58%, p < 0.001), and the association remained after adjustment for age, inflammation markers and ALAT. There was a dose-response relationship between protein S activity and clinical severity (Kendall_tau coefficient = -0.320, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001) or pulmonary damage on CT scan (Kendall_tau coefficient = -0.290, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001). High neutrophil count was also independently associated with death (p = 0.002). Conclusion. Protein S activity was lower in COVID-19 patients, and its level was associated with survival and disease severity, suggesting that it may have a role in the thrombotic manifestations of the disease.