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What Role Does Microthrombosis Play in Long COVID?
Toshiaki Iba1, Jean M Connors2, Jerrold H Levy3
1Department of Emergency and Disaster Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Insights
Long COVID, or post-acute sequelae of COVID-19 (PASC), affects 10-20% of patients. While microclots are a potential cause, PASC is complex and requires symptom-specific treatments.
Area of Science:
- Medical Research
- Infectious Diseases
- Pathophysiology
Background:
- Post-acute sequelae of COVID-19 (PASC), commonly known as long COVID, affects 10-20% of recovered patients.
- Persistent symptoms include fatigue, cognitive issues, and muscle weakness.
- The exact pathophysiological mechanisms underlying PASC remain largely unknown.
Purpose of the Study:
- To explore the potential role of persistent microclots in the development of long COVID.
- To review the current understanding of PASC pathophysiology and treatment strategies.
Main Methods:
- Review of existing literature on COVID-19 pathophysiology, thromboinflammation, and PASC.
- Analysis of studies investigating microclots, viral persistence, and treatment outcomes.
Main Results:
- Hypercoagulability and thrombosis are key in acute COVID-19, with ongoing thromboinflammation possibly linked to persistent viral elements.
- Microclots are hypothesized to contribute to PASC symptoms, but evidence is inconclusive.
- Current treatments targeting coagulation and vascular protection show inconsistent benefits.
Conclusions:
- Post-acute sequelae of COVID-19 (PASC) is a heterogeneous condition, not solely explained by microclots.
- Future research should focus on clarifying the pathomechanisms of individual symptoms.
- A stratified approach based on symptoms or biomarkers is recommended for effective PASC management.
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.
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