SARS-CoV-2 infection, hypercoagulability and hereditary thrombophilia factors

ABSTRACT

Coronavirus disease (COVID-19) is a potentially fatal infectious disease caused by the SARS-CoV-2 virus, a virus of zoonotic origin (1). It has been observed that clinical manifestations of SARS-CoV-2 infection range from asymptomatic disease to severe viral pneumonia accompanied by severe respiratory failure and may result in death (2). The most common initial symptoms of COVID-19 disease are fever, cough, and fatigue. Transmission primarily occurs through direct contact or droplets spread from an infected person (1). The binding of a receptor expressed by host cells is the first step of viral infection. Lung epithelial cells are thought to be the primary target of the virus. Most of the used drugs are drugs used in the treatment of other diseases, and their effectiveness in the treatment of COVID-19 is still at the research level. Specific anti-infection drugs are under development for potential treatment in humans (1). Veklury (Remdesivir) is the first treatment for COVID-19 to receive FDA approval. It is used in adults and pediatric patients [12 years and older and at least 40 kilograms] for the treatment of COVID-19 requiring hospitalization (3). The treatment of COVID-19 in our country is carried out by the recommendations of the Ministry of Health's Guide 'COVID-19 (SARS-CoV-2 infection)' prepared by the recommendations of the Coronavirus Science Council and updated by the developments (4). All of the drugs recommended in the manual are used under the approval of the Ministry of Health within the framework of non-indication drug use. In this pandemic, where new waves are constantly coming, scientists have succeeded in developing a large number of COVID-19 vaccine types in a short time as a result of intensive studies. The mRNA-based Pfizer-BioNTech COVID-19 vaccine is the first FDA-approved vaccine [23.08.2021] (5). The information about the COVID-19 disease, which is spreading rapidly around the world, is increasing with new researches day by day. Thrombophilia is a hypercoagulable condition that predisposes patients to thrombosis. It is a multifactorial condition that can result from genetic factors, acquired factors, or a combination of both. The prothrombin gene (F2), factor V Leiden (F5), and PAI-1 are important biomarkers of thrombophilia. Patients with multiple gene defects have a high risk of thrombosis (6). It is known that thromboembolic events can develop in patients with COVID-19 and the incidence of death increases accordingly. Studies have shown that VTE can be induced in patients with COVID-19 and severe pneumonia, and the incidence of VTE in COVID-19 patients hospitalized in the intensive care unit due to severe pneumonia has been reported to be high (7). The risk of thrombosis and arterial and venous thromboembolic complications seen in 30% of hospitalized subjects due to Novel Coronavirus pneumonia has been reported in many studies, which can be explained by the prolonged inflammatory response, decreased physical activity during infection, and reduced oxygen levels in the circulation (6). Thrombotic and microangiopathic effects of the SARS-CoV-2 virus have been reported in COVID-19 patients (8). Circulatory disorders in the toes of COVID-19 patients are also reported as 'Covid toe (acro ischemia)' (9). Although it is reported that the disease progresses more severely in the elderly, patients with sub-diseases, and smoking history, it is also observed that the clinical course is severe and patient losses are experienced in young patients who do not have any underlying disease. The mechanisms of the development of thromboembolic events are the binding of the virus to the ACE-2 receptor and/or direct endothelial damage, activation of inflammatory and microthrombotic pathways as a result of endothelial damage by complement activation as in sepsis, and stasis due to hospitalization and immobility (10). DIC clinic may develop in patients with severe clinical course. The pathophysiology of DIC is reported to be complex and multifactorial, involving the interaction between the hemostatic system and components of the innate immune response to the infecting pathogen (11). However, there is no comprehensive research on inherited thrombophilia factors that may affect the hemostatic system. Severe clinical course in young patients, a similar clinical course in individuals from the same family even though they are in different cities, elderly patients recovering from the clinic safely and being discharged, VTE in different locations in COVID-19 patients, microangiopathic thrombus, etc. monitoring of the findings, the use of anticoagulants due to their positive contributions in treatment are included in the observations in this process. In the light of all this information, it is aimed to examine and reveal the possible relationship between the genetic variations evaluated in the thrombophilia panel and COVID-19 and presented with the literature data findings and recent studies. Gralinski et al. suggested that PAI-1 plays a protective role against infection in the viral pathogenesis studies of SARS-coronavirus disease (12). In another study, no statistically significant difference in thrombophilia polymorphic biomarkers between the severely ill COVID-19 group and the healthy population was found (6). Various studies that will provide new information on the subject are also actively continuing. In conclusion, thrombosis is frequently seen in severe COVID-19 patients. Essentially, the determination of the thrombophilia profile can assist in determining bleeding risk, mortality, ARDS incidence, and admission to the ICU. Latent genetic risk factors for thrombotic events may affect the outcome of COVID-19. Therefore, the identification of these factors may be useful for understanding the various COVID-19 outcomes and assessing COVID-19 patients' risk of thrombosis, severe disease, and vaccination policies.