Pathophysiological mechanisms of disease severity in COVID-19: An update

The pandemic of COVID-19 has created a confounding global health crisis with more than 25 million cases and 870,000 deaths worldwide. The novel coronavirus, SARS-CoV-2, exploits the human ACE2 receptor and potential CD147 to invade a plethora of organ systems including cardiovascular, renal, endocrine, nervous, and gastrointestinal. The pathophysiological mechanisms of COVID-19 infection were found to be associated with the direct viral invasion, dysregulated renin-angiotensin-aldosterone system (RAAS), hypoxia, hyperinflammation, cytokine storm, endotheliopathy, and thrombosis. Emerging evidence suggests that the kinin-kallikrein system, iron dysregulation, and complement component C5a anaphylatoxin have roles in disease severity. In critical patients, the effects manifest as acute respiratory distress syndrome (ARDS), lymphopenia, acute kidney injury (AKI), disseminated intravascular coagulation (DIC), hypovolemic shock leading to multiorgan dysfunction syndrome (MODS). In this review, we provided an update on the pathophysiology of COVID-19 with an emphasis on the clinical outcomes in severe patients that will help facilitate a deeper understanding of the disease.