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In lack of obvious clinical evidences when it comes to pathogenesis of COVID-19, comparative analysis of earlier pandemic HCoVs linked immunological reactions can provide insights into COVID-19 pathogenesis. In this review, we summarize the possible source and transmission mode of CoVs in addition to current comprehension from the viral genome integrity of known pandemic virus against SARS-CoV-2. We also consider the host protected response and viral evasion based on offered medical evidence