Proteinase-activated PAR4 receptors and hemostasis in COVID-19: 616.24-002.153

Abstract

Summary. Background. Proteinase-activated receptors (PAR) are present on platelets, neutrophils, alveolar epithelium, and endothelial cells, which activation is essential in the development of thromboinflammation upon infection with the SARS-CoV-2 virus. Objectives: to study PAR4 level, the activity of neutrophil elastase, trypsin-like proteinases, and hemostasis parameters in community-acquired pneumonia under COVID-19. Patients/Methods. The study included 92 patients with community-acquired bilateral pneumonia under a novel coronavirus infection COVID-19. The control group consisted of 15 apparently healthy individuals with negative result of the polymerase chain reaction (PCR) for SARS-CoV-2 RNA, and without serum antibodies associated with SARS-CoV-2. PAR4 level, C-reactive protein (CRP), neutrophil elastase activity, trypsin-like proteinases, hemostasis parameters were determined in patients upon admission to the hospital and in practically healthy individuals undergoing preventive examination. Results. On admission, in 44 patients acute respiratory distress syndrome (ARDS) was diagnosed, glucocorticoids were prescribed to 19 patients. On the first day of hospitalization in patients with COVID-19, PAR4 level increased, especially in the presence of ARDS (pO2 < 95 mm Hg) and was 1.75 times higher than in practically healthy individuals. PAR4 increasing was accompanied by a 12-fold increasing of CRP, and by 8.6-fold increasing of trypsin-like proteinases. On the first day of infection in 20% of patients, a decrease in PAR4 level was detected, while CRP level increased by 17.8 times, trypsin-like proteinases — by 9.8 times, and the activity of neutrophil elastase increased by 3.7 times regarding healthy persons. PAR4 decreasing was accompanied by increasing of prothrombin time by 6.7 times and fibrinogen level by 2 times. Individuals with low PAR4 level at admission later developed severe COVID-19 with a fatal outcome at 2–3 weeks of infection. Conclusions. A change in PAR4 level on the first day of hospitalization may be an early sign of an unfavorable course of COVID-19. Increasing of PAR4 level is associated with the presence of ARDS before the onset of signs of impaired hemostasis. PAR4 decreasing is associated with a maximum increasing of CRP content, neutrophil elastase activity, trypsin-like proteinases, prothrombin time, and fibrinogen level in the early stages of the disease, followed by a fatal outcome.

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