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

Abdul Muhaymin, Hyder Wajid Abbasi, Naeem Ullah, Adnan Haider, Syed Babar Jamal, Fazli Subhan, Muhammad Naeem


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.

Key Words: ACE2, COVID-19 Pathogenesis, Cytokines Storm, Extrapulmonary Manifestations.

How to cite this: Muhaymin A, Abbasi HW, Ullah N, Haider A, Ja,mal SB, Subhan F, Naeem M. Pathogenesis of COVID-19: ACE2, Cytokine Storm and Extrapulmonary Manifestations. Life and Science. 2021; 2(4): 189-197.  doi:

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