In the conditions of steadily increasing urbanization and emerging negative microclimates, there is increase the morbidity of children in megacities. The damaging effect of environmental factors causes the development of “minimal persistent inflammation” of mucosa. We had studied 55 children in age 1–8 years suffering from recurrent ARVI associated with different chronic HVI (HSV I/II, EBV, CMV, HHV VI) and chronic recurrent bacterial diseases. The comparison group was 40 conditionally healthy children, comparable by sex and age. Clinical and immunological methods: ELISA, PCR, cytofluorimetry were used. We studied 2 groups of children: 1 group – 1–4 years old (early children) and 2 group – 5–8 years old, suffering from recurrent ARVI of a high rate of frequency. Clinical and anamnestic data showed that the incidence of ARVI was in 1 group – 7–15 and in 2 groups – 7–24 or more episodes per year, and the duration of these episodes was: 7.5 and 15.8 days, respectively. In all children, repeated ARI in combination with chronic respiratory diseases with frequent exacerbations were associated with recurrent and/or mono- and mixed HVI. Comparative analysis showed that in the children from group 1 demonstrate deficient in IFN-α, serum IgA and various NG disorders. However more severe disorders in IFN-α, NK-cells, NG system were detected in group 2, which is associated with a greater age of infectious history. Our study revealed the urgency to create new approaches for targeted immunoprophylaxis for immunocompromised children living in the megapolis. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.