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

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 12081
• Main Authors: Higashikuni, Yasutomi, Liu, Wenhao, Obana, Takumi, Sata, Masataka
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 08.11.2021; MDPI
• Subjects: Cardiovascular diseases; Coronaviruses; Cough; COVID-19; endothelial injury; Fever; Impact analysis; inflammation; Interferon; Kinases; Lymphocytes; Lymphocytes T; Middle East respiratory syndrome; Morbidity; Pathogenesis; platelet activation; Public health; Respiratory distress syndrome; Review; Risk analysis; Risk factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; therapeutics; Thromboembolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222112081

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.