Interleukins in COVID-19 and SARS-CoV-2 Variants: Immunopathogenesis, Therapeutic Perspectives and Vaccine-Induced Immune Responses

DOI record: { "DOI": "10.3390/ijms27031391", "ISSN": [ "1422-0067" ], "URL": "http://dx.doi.org/10.3390/ijms27031391", "abstract": "<jats:p>The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by profound immune dysregulation where interleukins play a central role in determining disease severity and response to interventions. This review summarizes the role of interleukins in the immunopathogenesis of COVID-19, with particular emphasis on differences observed across major SARS-CoV-2 variants. Pro-inflammatory interleukins like IL-1β, IL-6, IL-2, IL-17 and IL-18 are critically involved in cytokine storm, hyperinflammation, and acute respiratory distress syndrome, whereas anti-inflammatory cytokines like IL-10 contribute to immune regulation and resolution of inflammation. Elevated levels of IL-1α, IL-1β, IL-4, IL-8, IL-9, IL-16, IL-18 have been documented in the Delta variant as compared with the Omicron variant, with IL-6 being the most frequent interleukin reported to be increased across all SARS-CoV-2 variants relative to the ancestral Wuhan strain. Elevated IL-2, IL-4, IL-6, and IL-10 levels have been associated with Omicron sub-variants. The review encompasses interleukin-based therapeutic strategies, where several IL-1 and IL-6 inhibitors were studied across clinical trials, but only tocilizumab has shown some promise against severe COVID-19. IL-2, IL-6, IL-15 and IL-21 levels were positively correlated with IgG and neutralizing antibody activity after vaccination with longevity of post-vaccination immunity being determined by IL-2 and IL-7.</jats:p>", "alternative-id": [ "ijms27031391" ], "author": [ { "affiliation": [ { "name": "Department of Microbiology, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, UP, India" } ], "family": "Mahajan", "given": "Supriya", "sequence": "first" }, { "affiliation": [ { "name": "Numed Super Speciality Hospital, Greater Noida 201306, UP, India" } ], "family": "Mahajan", "given": "Saurabh", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Microbiology, School of Medical Sciences and Research, Sharda University, Greater Noida 201306, UP, India" } ], "family": "Gusain", "given": "Akanksha", "sequence": "additional" } ], "container-title": "International Journal of Molecular Sciences", "container-title-short": "IJMS", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 1, 30 ] ], "date-time": "2026-01-30T11:09:22Z", "timestamp": 1769771362000 }, "deposited": { "date-parts": [ [ 2026, 1, 30 ] ], "date-time": "2026-01-30T11:12:09Z", "timestamp": 1769771529000 }, "indexed": { "date-parts": [ [ 2026, 1, 30 ] ], "date-time": "2026-01-30T21:45:31Z", "timestamp": 1769809531612, "version": "3.49.0" }, "is-referenced-by-count": 0, "issue": "3", "issued": { "date-parts": [ [ 2026, 1, 30 ] ] }, "journal-issue": { "issue": "3", "published-online": { "date-parts": [ [ 2026, 2 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 1, 30 ] ], "date-time": "2026-01-30T00:00:00Z", "timestamp": 1769731200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1422-0067/27/3/1391/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "1391", "prefix": "10.3390", "published": { "date-parts": [ [ 2026, 1, 30 ] ] }, "published-online": { "date-parts": [ [ 2026, 1, 30 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1016/j.mib.2014.05.005", "article-title": "To sense or not to sense viral RNA—Essentials of coronavirus innate immune evasion", "author": "Kindler", "doi-asserted-by": "crossref", "first-page": "69", "journal-title": "Curr. 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