Pathogenesis of COVID-19: ACE2, Cytokine Storm and Extrapulmonary Manifestations

Abstract

The coronavirus disease 19 (COVID-19) is a global pandemic of the twenty-first century and currently fourth
wave is creating fear and panic worldwide. It is caused by severe acute respiratory syndrome coronavirus 2
(SARS-COV-2), a highly contagious viral infection of humans. The COVID-19 can be spread mainly through
respiratory droplet particles and in contact with a COVID-19 infected person. Clinical manifestation of COVID-19
patients includes cough, fever, diarrhea, loss of taste and smell. In critical cases of COVID-19, the development
of pneumonia and dyspnea leads to acute respiratory distress syndrome that may cause the death of the
patient. It is well established that Angiotensin-Converting Enzyme 2 (ACE2) receptors on alveolar cells act as an
entry gate for the SARS-COV-2. However, ACE2 is also highly expressed in multiple extrapulmonary vital organs
such as the gastrointestinal system, cardiovascular system, kidney, etc. Therefore, the direct viral entry in these
organs can be a likely pathway of injury. In addition, decoupling of immune responses leads to the cytokines
storm, which might contribute to the injury of extrapulmonary organs. In this review, we report the multiple
organ pathogenesis and clinical manifestations of COVID-19 patients, which could aid clinicians and researchers
in prioritizing therapeutics remedies and developing research for all vital body systems involved.