What Role Does Microthrombosis Play in Long COVID?

Abstract

Soon after the outbreak of coronavirus disease 2019 (COVID-19), unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness were reported in patients who had recovered from acute COVID-19 infection. This abnormal condition has been recognized as “long COVID (postacute sequelae of COVID-19 [PASC])” with a prevalence estimated to be from 10 to 20% of convalescent patients. Although the pathophysiology of PASC has been studied, the exact mechanism remains obscure. Microclots in circulation can represent one of the possible causes of PASC. Although hypercoagulability and thrombosis are critical mechanisms of acute COVID-19, recent studies have reported that thromboinflammation continues in some patients, even after the virus has cleared. Viral spike proteins and RNA can be detected months after patients have recovered, findings that may be responsible for persistent thromboinflammation and the development of microclots. Despite this theory, long-term results of anticoagulation, antiplatelet therapy, and vascular endothelial protection are inconsistent, and could not always show beneficial treatment effects. In summary, PASC reflects a heterogeneous condition, and microclots cannot explain all the presenting symptoms. After clarification of the pathomechanisms of each symptom, a symptom- or biomarker-based stratified approach should be considered for future studies.

Editorial Compilation—XV

“…For the current compilation issue, we start with the contribution from Iba and colleagues. 1 As already noted, unexplained sustained fatigue, cognitive disturbance, and muscle ache/weakness are reported in patients who have recovered from an acute COVID-19 infection. This adverse condition, termed long-COVID or PASC, has a prevalence estimated to be around 10 to 20% of convalescent patients.…”

“…This issue begins with several manuscripts still focused on COVID-19 (coronavirus disease 2019) or its potential aftermath, a condition colloquially called “long-COVID,” and otherwise known as “post-acute sequelae of COVID-19 (PASC).” 1 2 3 Long-COVID represents a heterogeneous clinical syndrome characterized by a pathologic continuum of signs, symptoms, and also laboratory/radiologic abnormalities that may persist for a long time after recovering from an acute SARS-CoV-2 (severe acute respiratory syndrome-coronavirus disease 2) infection. Among the various components of this post-viral condition, the risk of venous thromboembolism (VTE) in patients hospitalized for COVID-19 remains considerably higher after discharge, especially in the earlier period (i.e., within the first 6–12 months), in older individuals, in men, in patients with longer hospital stays and more aggressive clinical management (e.g., mechanical ventilation and/or intensive care), when thromboprophylaxis is not used, and in those with a persistent pro-thrombotic state.…”

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Evolving from the Post COVID-19 Syndrome

“…A recent study identified a disturbed retinal microcirculation to be strongly associated with PCS and ME/CFS, which may serve as a potential marker for microcirculatory disorders [10,42]. Notably, the thrombo-inflammatory status persists months after the patient has recovered and the virus has cleared [5,40,43]. Therefore, malformed blood cells, microclots, and thrombo-inflammation can potentially impede capillary perfusion and promote a microcirculatory disorder and thus impair organ blood supply via capillary obstruction [9].…”

The Effect of Antiplatelet Therapy on COVID-19

“…Predominant roles of platelets contributing to the development of vaccine-induced immune thrombotic thrombocytopenia (VITT) are also recognized in conjunction with the polyanion from the vaccine component 3) (Figure 1). Moreover, there is speculation about the potential involvement of activated platelets in the pathogenesis of the condition known as 'Long COVID' 4) .…”