The outbreak of Severe Acute Respiratory Syndromes Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with co-morbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of ACE2 receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed that during the receptor-recognition (beginning of infection), interferon, protease and followed by cytokine induction, hypoxia plays a significant role in the context of the balance of ACE/ACE2. It has also been very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.

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