Indicators of the innate immune system in patients with severe COVID-19 and their role in the development of coagulopathy

SARS-CoV-2 is one of the few viruses that cause blood coagulation disorders. The pathogenesis of coagulopathies in COVID-19 is polyetiological: cytokine storm, NETosis, dysfunction of the renin-angiotensin system, thrombotic microangiopathy, disseminated intravascular coagulation (DIC), and hypofibrinolysis. However, the role of the immune system in the development of these disorders remains insufficiently described.

The aim. To characterize the role of the innate immune system in the development of coagulopathies in patients with severe COVID-19.

Methods. The study included a cohort of 103 patients with severe COVID-19 receiving anticoagulant therapy and undergoing treatment in Chita, Russia. Hemostasis was assessed using thrombodynamics testing, as well as measurement of fibrinogen, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1). All patients with SARS-CoV-2 were stratified into four subgroups based on their hemostatic status. Levels of tissue factor (TF), D-dimer, tPA, PAI-1, myeloperoxidase (MPO), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and cystatin C were determined by flow cytometry.

Results. In the pronounced hypercoagulation and hypercoagulation groups, elevated fibrinogen levels were observed, along with a parallel increase in tPA concentration and a sharp rise in PAI-1 levels. Meanwhile, maximal TF-values were recorded in patients with hypocoagulation. MMP-2 levels were lower than those in the control group in all COVID-19 patients, but progressively increased from normocoagulation to hypocoagulation, reaching a maximum in the latter group. MMP-9 and MPO concentrations were elevated across all groups, peaking in the normocoagulation group. Cystatin C concentration was increased in all patients.

Conclusion. Severe COVID-19 is associated with the development of thrombotic coagulopathy, driven by the formation of a vicious cycle of “thromboinflammation,” in which hemostatic disorders and systemic inflammatory response mutually reinforce each other.

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