This brief analytical review is devoted to spreading, etiology, pathogenesis, prophylaxis, and treatment of COVID-19 and "swine flu" causing pandemics in the 21st century. Both pandemics were caused by respiratory viruses belonging to different families, i.e., Coronaviridae (SARS-CoV-2) and Orthomyxoviridae (influenza A(H1N1)pdm09 virus), respectively. In most cases, pathogens enter human organisms via epithelial cells of the upper airways. Sometimes, these viruses infect intestinal epithelium. Given that symptoms of influenza and COVID-19 are similar, its diagnostics should always be based on laboratory results, especially, PCR evidence for specific RNA presence in clinical material. The paper describes similarities and differences in immune pathogenesis of the diseases. The main characteristics of two pandemic courses caused by SARS-CoV-2 and influenza A(H1N1)pdm09 are revealed. The presence of influenza vaccine and etiotropic chemotherapeutic agents, as well as preexisting immunity to influenza virus among elderly people in 2009 had a significant influence on morbidity and mortality during the influenza pandemic. The presence of antibodies to A(H1N1)pdm09 virus in sera of elderly people before the pandemic can be explained by the fact that some antigenic properties of A(H1N1) virus which circulated before 1957 were similar to that of A/California/07/09 (H1N1)pdm09. Consequently, morbidity and mortality among people older than 65 (main risk group) were low, while children and young adults suffered more often. The opposite pattern is observed for COVID-19, since mortality among the elderly population is high, while the children and young adults have an asymptomatic or mild form of a disease. A suggestion is made that population in the South-East Asia may have immunity against SARS-CoV-2, since coronaviruses with antigenic features similar to the pandemic one could circulate in that region and infect population without evident symptoms, while one or several recent virus variants caused severe disease and COVID-19 outbreak in Wuhan. © 2020 Russian Association of Allergologists and Clinical Immunologists, St. Petersburg Regional Branch (SPb RAACI). All rights reserved.