| Summary: | Background: Research on the subject of the influence of SARS-CoV-2 mechanisms on human homeostasis remains an actual problem. Particular interest is the study of pathomorphological changes in the appendix in children with COVID-19. Objectives: Aim of this study: morphological and molecular biological evaluation of the appendix in children of different age groups with COVID-19. Methods: Groups were formed on the basis of anamnestic, clinical, and morphological data: I (<i>n</i> = 42; aged 2 to 18 years, average age—10.8 ± 4.79)—with an established clinical diagnosis: coronavirus infection (COVID-19; PCR+); II (<i>n</i> = 55; aged 2 to 18 years, average age—9.7 ± 4.77)—with a confirmed clinical diagnosis of acute appendicitis; collected before the onset of the COVID-19 pandemic in 2017–2019; and III (<i>n</i> = 38; aged 2 to 18 years, average age—10.3 ± 4.62)—the control group. Histological and immunohistochemical studies were conducted using primary antibodies to CD3, CD4, CD68, CD163, CD20, and CD138 and to pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Results: In most samples of appendixes in children with COVID-19, signs of destructive phlegmonous–ulcerative and gangrenous appendicitis were discovered. An increase in CD3+, CD4+, CD68+, CD163+, and CD20+ CD138+ immunocompetent cells was found in the appendix of children with COVID-19. As well, there was an increase in pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Conclusions: The aforementioned pathological and immunohistochemical changes were more pronounced in the group of children aged 6–12 years (childhood).
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