Platelets in COVID-19: “innocent by-standers” or active participants?

Abstract

One of the most dangerous features of the new coronavirus infection caused by the SARS-CoV-2 virus is the tendency of the hemostasis system of patients to excessive thrombus formation. Among the possible causes of this pathology, both the activation of vascular endothelial cells, leading to the exposure of tissue factor by these cells, and direct activation of the plasma hemostasis were named. Besides, there is a significant change in platelet responses to activation, which is not accompanied by significant thrombocytopenia. The mechanism of platelet dysfunction is rather controversial. On the one hand, there are suggestions that platelets can act as a direct “container” for the virus, thus spreading it throughout the body. On the other hand, the presence of viral RNA in platelets has been demonstrated in only one study, while other authors have obtained the opposite result. Another mechanism of the virus's direct effect on platelets is the penetration of the virus into megakaryocytes and the subsequent violation of thrombocytopoiesis. However, three of the four published works show that platelets from patients with SARS-CoV-2 are in an activated state (the so-called platelet pre-activation). This phenomenon can be caused by the direct influence of the virus and the effect of thromboinflammation in the lungs on platelet functions. Here we review the known data and possible causes of the platelet functionality changes observed in patients with SARS-CoV-2.

Dissecting thrombus-directed chemotaxis and random movement in neutrophil near-thrombus motion in flow chambers

“…It is sometimes mixed with immunothrombosis-a process of thrombus formation at the site of immune cell accumulation and activation [8,9]. Platelets are anucleate fragments of megakaryocytes that circulate in human blood and play critical roles in both hemostasis and immunity [5,10]. When platelets are activated at the site of injury or inflammation, they release their granules, which contain P-selectin, fibrinogen, von Willebrand factor (VWF), growth factors, and chemoattractants for leukocytes [11][12][13].…”

Longitudinal multiparametric characterization of platelet dysfunction in COVID-19: Effects of disease severity, anticoagulation therapy and inflammatory status

“…It is believed that this coagulopathy originates from COVID-19induced cytokine storm [7,8], a significant increase of the amounts of inflammatory cytokines (IL-1b, IL-6, IL-8) in blood [9]. It has been demonstrated multiple times that cytokine storm is mediated by monocytes and neutrophils, which infiltrate patient lungs upon SARS-CoV-2 infection [2,10], release cytokines and cause endothelial dysfunction and subsequent activation of blood coagulation [11,12].…”

A strong correlation exists between platelet consumption and platelet hyperactivation in COVID-19 patients. Pilot study of the patient cohort from CCH RAS Hospital (Troitsk).

“…In patients with the severe form of the disease, there is an association with interstitial pneumonia, thrombosis, and subsequent pulmonary failure [2], [3]. Thrombocytopenia was also shown to be common in COVID-19 patients, and lower platelet count correlated with disease severity and higher mortality rates [4]- [6]. COVID-19 is known to cause a strong inflammatory response, the cytokine storm characterized by increased concentrations of interleukins 1β, 6, and 8, among others [7].…”

“…The angiotensin-converting enzyme 2 (ACE-2) receptor [8] is the key route for SARS-CoV-2 entrance into human cells. However, it is not clear if this receptor is present on platelets [3], [6], [29], [30]. However, ACE2 presence on platelets is controversial, as there are both works confirming [29], [31] and denying [3] it.…”