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The outbreak of the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) all over the world has caused global public health emergencies, international concern and economic crises. The systemic SARS-CoV-2 disease (COVID-19) can lead to death through causing unrestrained cytokines-storm and subsequent pulmonary shutdown among the elderly and patients with pre-existing comorbidities. Additionally, in comparison with poor nations without primary health care services, in developed countries with advanced healthcare system we can witness higher number of infections per one million people. In this review, we summarize the latest studies on genes associated with SARS-CoV-2 pathogenesis and propose possible mechanisms of the virus replication cycle and its triggered signaling pathways to encourage researchers to investigate genetic and immune profiles of the disease and try strategies for its treatment. Our review shows that immune response in people with different genetic background might vary as African and then Asian populations have lowest number of affected cases compared with European and American nations. Considering SARS-CoV-2 pathogenesis, we put forward some potentially important genetic gateways to COVID-19 infection including genes involved in the entry and replication of SARS-CoV-2 and the regulation of host immune response which might represent explanation for its spread, severity, and morality. Finally, we suggest that genetic alterations within these gateways could be critical factors in influencing geographical discrepancies of the virus, so it is essential to fully study them and design appropriated and reliable therapeutic agents against COVID-19.
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