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Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G\/A and IFNG +874T\/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G\/A, n = 497; IFNG +874T\/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G\/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T\/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T\/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.<\/jats:p>","DOI":"10.3390\/v16040650","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T09:53:52Z","timestamp":1713779632000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of the IFNG +874T\/A Polymorphism with Symptomatic COVID-19 Susceptibility"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0776-6212","authenticated-orcid":false,"given":"Kevin Matheus Lima de","family":"Sarges","sequence":"first","affiliation":[{"name":"Laboratory of Genetics of Complex Diseases, Institute of Biological Sciences, Federal University of Par\u00e1, Belem 66000-000, Brazil"},{"name":"Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Belem 66000-000, 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Diseases, Institute of Biological Sciences, Federal University of Par\u00e1, Belem 66000-000, Brazil"},{"name":"Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Belem 66000-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3620-3470","authenticated-orcid":false,"given":"Mauro de Meira","family":"Leite","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics of Complex Diseases, Institute of Biological Sciences, Federal University of Par\u00e1, Belem 66000-000, Brazil"},{"name":"Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Belem 66000-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Karoliny da Silva","family":"Torres","sequence":"additional","affiliation":[{"name":"Graduate Program in Biology of Infectious and Parasitic Agents, Federal University of Par\u00e1, Belem 66000-000, 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