SandBox

Pathophysiology

• Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions.
• Among patients with COVID-19, there is a high prevalence of the cardiovascular disease, and >7% of patients experience myocardial injury from the infection.
• Myocarditis is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause.
• The major cause of myocarditis in the United States and other developed countries is viral. Number of cases of myocarditis have been reported in COVID19 patients.
• It has also been reported as the cause of death in some COVID19 patients.

• SARS-CoV-2 infection is caused by binding of the viral surface spike protein (primed by TMPRSS2, which is a trans-membrane protease, serine 2) to the human angiotensin-converting enzyme 2 (ACE2) receptor.
• ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry.
• ACE2 is highly expressed in the heart as well.
• Naive T lymphocytes can be primed for viral antigens via antigen-presenting cells and cardio-tropism by the heart-produced hepatocyte growth factor (HGF) which binds c-Met, an HGF receptor on T lymphocytes.
• The viral RNAs of Middle East Respiratory Syndrome coronavirus (MERS-CoV) and SARS-CoV were found in the heart tissues of infected animals, suggesting that these corona viruses possess cardio-tropism.
• The primed CD 8+ T lymphocytes migrate to the cardiomyocytes and through cell-mediated cytotoxicity, cause myocardial inflammation.
• In the cytokine storm syndrome, pro-inflammatory cytokines such as Interleukin-6 (IL-6) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines.
• This results in a positive feedback loop of immune activation and myocardial damage.