Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation

Abstract

Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.

The Effect of Long Coronavirus Disease on Obesity and the Role of Korean Medicine

“…SARS-CoV-2는 혈관 31,32) , 심장 33) , 간 34,35) , 췌장 36,37) , 신장 38,39) 등과 같은 다양한 대사 관련 장 기에 침입하여 장기의 기능을 저하시킨다 40,41) . 또한 혈관 손상으로 인해 혈전이 형성되어 미세혈관 기능 장애 및 전 신 염증을 유발한다 42) . 지방조직에는 지방세포 뿐만 아니라 대식세포를 비롯한 면역세포들이 존재하는데 전신 염증 상태에서 혈액 내에서 증가된 IL-1β, IL-6, tumor necrosis factor-alpha 등이 면역세포들을 활성화시켜 지방조직의 국 소적인 염증을 심화시키고 지방세포의 분화, 성숙, 사멸을 조절하며 전신적인 인슐린 저항성을 유발한다 2,29) .…”

“…저산소증 은 지방 조직에서 hypoxia-inducible factor 1 alpha를 통해 당 분해, 혈관 신생, 염증을 촉진시킴으로써 비만과 대사 기능에 큰 영향을 미친다 73,74) . 한편 SARS-CoV-2 감염으로 인한 혈관염과 전신 염증이 응고 장애를 유발, 혈전증과 그로 인한 저산소증이 속발되고 이는 롱코비드의 주요 병 리 기전으로 여겨진다 42) .…”

Childhood Immunity and Infections: Time to Consider Endothelial Cells and Platelets

“…In the Multisystem Inflammatory Syndrome (MIS-C), an exaggerated immune response leads to the development of a severe disease characterized by high fever, inflammatory markers, and a procoagulation state [ 6 ]. Moreover, growing evidence supports a primary role of the immune system and endothelial/coagulation pathways in the genesis of Long COVID in a subgroup of patients [ 7 ]. Last, differences in immune responses to vaccinations and infection are creating extremely variable susceptibility to reinfections in people of all age groups [ 8 ].…”

“…While COVID-19 was initially considered a respiratory disease, there is now evidence that this is a systemic inflammatory condition characterized by viral invasion potentially in most parts of the organism and endothelial inflammation. Laboratory parameters of endothelial phlogosis and activation of the coagulation cascade is a hallmark of the disease, which has thromboembolic events and myocarditis as a cornerstone of the infection [ 6 , 7 , 8 ]. Conversely, these events are much less frequent in children during COVID-19.…”

“…In the rare circumstance when children develop MIS-C after SARS-CoV-2 infection, D-Dimers are characteristically high, children have myocardial dysfunction or coronary involvement, and are mostly treated with anti-coagulants or anti-aggregants [ 6 ]. In Long COVID, chronic inappropriate endothelial and platelet activation, lung hypoperfusion and microclots have been clearly demonstrated [ 7 , 9 ]. Last, a specific group of people (young males) in a minority of cases can develop myocarditis as the main complication of mRNA anti-COVID vaccination [ 8 ], suggesting again a close relationship with cells interfacing with the blood.…”