Many severe forms of COVID-19 have genetic causes, with variants providing information and thus supporting the hypothesis that moderate-intensity exercise would have a prophylactic role. In the case of genetic abnormalities related to the induction and amplification of type I interferons, in addition to curative administration of interferon, moderate intensity exercise could be used prophylactically. The same exercises inhibit the p38 MAPK pathway, being evaluated by clinical trials the drug inhibition of that pathway. In high physically active subjects, intermediate CCR2 monocyte decreased in response to moderate intensity exercise, and Cenicriviroc, an antagonist of the chemokine CCR5/CCR2b receptor, has been proposed for therapy. Exercise prevents the increased expression of Tyk2, and for COVID-19 therapy, corresponding to the defect of this gene, kinase inhibitors or Baricitinib have been proposed. The critical analysis of the data presented in the paper shows that for the prophylaxis of severe forms of COVID-19, moderate intensity exercises could be used.