COVID-19-Associated Coagulopathy: An Exacerbated Immunothrombosis Response

Abstract

Since the onset of the global pandemic in early 2020, coronavirus disease 2019 (COVID-19) has posed a multitude of challenges to health care systems worldwide. In order to combat these challenges and devise appropriate therapeutic strategies, it becomes of paramount importance to elucidate the pathophysiology of this illness. Coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a dysregulated immune system and hypercoagulability. COVID-associated coagulopathy (CAC) was recognized based on profound d-dimer elevations and evidence of microthrombi and macrothrombi, both in venous and arterial systems. The underlying mechanisms associated with CAC have been suggested, but not clearly defined. The model of immunothrombosis illustrates the elaborate crosstalk between the innate immune system and coagulation. The rendering of a procoagulant state in COVID-19 involves the interplay of many innate immune pathways. The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system. Activated leukocytes potentiate a procoagulant state via release of intravascular tissue factor, platelet activation, NETosis, and inhibition of anticoagulant mechanisms. Additional pathways of specific relevance in CAC include cytokine release and complement activation. All these mechanisms have recently been reported in COVID-19. Immunothrombosis provides a comprehensive perspective of the several synergistic pathways pertinent to the pathogenesis of CAC.

Cutaneous Manifestations in Adult Patients with COVID-19 and Dermatologic Conditions Related to the COVID-19 Pandemic in Health Care Workers

“…Based on autopsy findings, SARS-CoV-2 infection causes both macrovascular and microvascular thrombi in organ system vasculature including the cardio-pulmonary, renal, central nervous, and integumentary systems [64][65][66]. One proposed mechanism involves a cytokine storm reaction in which macrophage-induced inflammation leads to a pro-thrombotic state [67].…”

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19

“…One of the most common complications is an acute respiratory distress syndrome (ARDS) resulting from the cytokine storm phenomenon, a violent and uncontrolled inflammatory reaction in response to the presence of the virus in the host organism [ 1 , 2 , 16 , 23 ]. However, the negative consequences of COVID-19 are also connected with other disorders of the respiratory system [ 1 , 16 , 26 , 27 ], with the cardiovascular system (for review, see [ 1 , 16 , 22 , 26 , 28 , 29 , 30 ]) and with dangerous hematological complications, particularly thromboembolism [ 1 , 16 , 31 , 32 , 33 , 34 , 35 , 36 ]. In addition, pathological changes in the renal [ 1 , 16 , 27 , 33 , 37 , 38 ], gastrointestinal, hepatic, pancreatic [ 1 , 16 , 27 , 31 , 39 , 40 ] and nervous systems [ 1 , 27 , 41 , 42 , 43 ] have been described.…”

“…There is a significant association between severe COVID-19 and the occurrence of thromboembolism (for review, see [ 1 , 16 , 32 , 33 , 34 , 35 , 36 ]). Unfortunately, only a few publications have addressed the influence of CBD on the components or parameters of hemostasis.…”

The immune response to SARS-CoV-2. Focus on severe COVID-19 pathogenesis

“…This is clinically present as ARDS or AKI [39]. Both diseases, when fully presented are difficult to control even in the ICU settings [40][41][42][43]. Therefore, many strategies focused on prevention of complement activation are proposed as important aspects of COVID-19 treatment.…”