When an organism is exposed to a viral infection, a variety of pathologies develop over a long period and across multiple organs. This involves factors on the viral side, those on the host side, and social factors. Viral factors are defined by viral genome information, including viral genome mutations. Factors on the host side include epigenomic modifications acquired through aging and environmental factors, in addition to human whole-genome information. Social factors include lifestyle changes, such as exercise, diet, and conversation, due to epidemics of viral infections. In the chronic phase, more than 200 sequelae　(e.g., Long COVID) occur, including neurological symptoms (depression, cognitive impairment, and sleep disturbances). By integration of the basic, clinical, and systems biological analyses, we have shown the operating principles of host life systems in response to viral infection with coronaviruses (SARS-CoV and SARS-CoV2) and influenza viruses. In the present time, I would like to talk about the pathogenesis of severe viral infections and sequelae, and the possibility of drug discovery, focusing on our findings.