Pathogenic Basis of Thromboinflammation and Endothelial Injury in COVID-19: Current Findings and Therapeutic Implications

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with a great impact on social and economic activities, as well as public health. In most patients, the symptoms of COVID-19 are a high-grade fever and a dry cough, and spontaneously resolve within ten days. However, in severe cases, COVID-19 leads to atypical bilateral interstitial pneumonia, acute respiratory distress syndrome, and systemic thromboembolism, resulting in multiple organ failure with high mortality and morbidity. SARS-CoV-2 has immune evasion mechanisms, including inhibition of interferon signaling and suppression of T cell and B cell responses. SARS-CoV-2 infection directly and indirectly causes dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction, which interact with each other and are exacerbated by cardiovascular risk factors. In this review, we summarize current knowledge on the pathogenic basis of thromboinflammation and endothelial injury in COVID-19. We highlight the distinct contributions of dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction to the pathogenesis of COVID-19. In addition, we discuss potential therapeutic strategies targeting these mechanisms.

Yasutomi Higashikuni, M.D., Ph.D., FESC

Assistant Professor of Cardiovascular and Genetic Research

My research interests include homeostatic inflammation, RNA metabolism and modification, and synthetic biology.

Wenhao Liu, M.D.

Graduate Student

My research interests include inflammation, RNA metabolism, synthetic biology and heart failure with preserved ejection fraction.

Takumi Obana

Technical Assistant

My research interests include artificial organs, biomaterials, and extremophiles.