Autoimmune diseases associated with SARS-CoV-2: pathogenetic mechanisms and clinical spectrum
DOI:
https://doi.org/10.11603/1681-2727.2026.3.16578Keywords:
SARS-CoV-2, autoimmune diseases, pathogenesisAbstract
Current data on the epidemiology, pathogenetic mechanisms, clinical spectrum, and risk factors for autoimmune diseases developing after SARS-CoV-2 infection are summarized. A narrative literature review was conducted according to PRISMA principles, with searches performed in PubMed/MEDLINE, Embase, the Cochrane Library, and Google Scholar. A total of 206 publications – including cohort studies, systematic reviews, meta-analyses, and case series – selected according to predefined inclusion and exclusion criteria were included in the analysis.
SARS-CoV-2 infection is associated with an increased risk of several autoimmune and immune-mediated diseases, with the magnitude of the association varying substantially according to the specific condition, disease severity, and study population. The main pathogenetic mechanisms include molecular mimicry between viral and human antigens, NETosis with complement activation, lymphopenia accompanied by proliferation of autoreactive lymphocytes, and reactivation of latent herpesviruses. A dose-dependent association between the severity of COVID-19 and the risk of autoimmunization was identified; newly developed autoantibodies persist for at least 12 months. Risk factors include female sex, age, obesity, and genetic predisposition. In children, type 1 diabetes mellitus and multisystem inflammatory syndrome predominate. Vaccination reduces the risk of post-COVID-19 complications.
References
1. Caso, F., Costa, L., Ruscitti, P., Navarini, L., Del Puente, A., Giacomelli, R., & Scarpa, R. (2020). Could SARS-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects? Autoimmunity Reviews, 19(5), 102524. https://doi.org/10.1016/j.autrev.2020.102524 DOI: https://doi.org/10.1016/j.autrev.2020.102524
2. Tesch, F., Ehm, F., Vivirito, A., Wende, D., Batram, M., Loser, F., Menzer, S., Jacob, J., Roessler, M., Seifert, M., Kind, B., König, C., Schulte, C., Buschmann, T., Hertle, D., Ballesteros, P., Baßler, S., Bertele, B., Bitterer, T., Riederer, C., Sobik, F., Reitzle, L., Scheidt-Nave, C., & Schmitt, J. (2023). Incident autoimmune diseases in association with SARS-CoV-2 infection: A matched cohort study. Clinical Rheumatology, 42(10), 2905–2914. https://doi.org/10.1007/s10067-023-06670-0 DOI: https://doi.org/10.1007/s10067-023-06670-0
3. Bøås, H., Lopez-Doriga Ruiz, P., Dahl, J., Gulseth, H. L., & Tapia, G. (2026). New-onset autoimmune disease following SARS-CoV-2 infection and mRNA vaccination in Norway: A retrospective cohort study. Journal of Internal Medicine, 299(2), 271–282. https://doi.org/10.1111/joim.70052 DOI: https://doi.org/10.1111/joim.70052
4. Wuller, S., Singer, N. G., Lewis, C., Karlson, E. W., Schulert, G. S., Goldman, J. D., Hadlock, J., Arnold, J., Hirabayashi, K., Stiles, L. E., Kleinman, L. C., Cowell, L. G., Hornig, M., Hall, M. A., Weiner, M. G., Koropsak, M., Lamendola-Essel, M. F., Kenney, R., Moffitt, R. A., Abedian, S., Esquenzi-Karonika, S., Johnson, S. G., Stroebel, S., Wallace, Z. S., & Costenbader, K. H. (2025). Severity of acute SARS-CoV-2 infection and risk of new-onset autoimmune disease: A RECOVER initiative study in nationwide U.S. cohorts. PLOS ONE, 20(6), e0324513. https://doi.org/10.1371/journal.pone.0324513 DOI: https://doi.org/10.1371/journal.pone.0324513
5. Goncalves, N., Mata, E., Capela, C., & Teixeira, P. M. (2021). The development or exacerbation of an autoimmune disorder associated with SARS-CoV-2 infection: A systematic review of case reports [Preprint]. Research Square. https://doi.org/10.21203/rs.3.rs-344958/v1 DOI: https://doi.org/10.21203/rs.3.rs-344958/v1
6. do-Nascimento, L. A., Machado, N. R., Bergamasco, I. S., Borges, J. V. da S., Sgnotto, F. da R., & Victor, J. R. (2025). Autoantibodies in COVID-19: Pathogenic mechanisms and implications for severe illness and post-acute sequelae. COVID, 5(8), 121. https://doi.org/10.3390/covid5080121 DOI: https://doi.org/10.3390/covid5080121
7. Dişli, F., Yılmaz, Y., & Yıldız, S. (2025). Magnitude of SARS-CoV-2 antibody production and its relationship with autoantibody formation. Infectious Diseases and Clinical Microbiology, 7(4), 435–445. https://doi.org/10.36519/idcm.2025.685 DOI: https://doi.org/10.36519/idcm.2025.685
8. Damoiseaux, J., Dotan, A., Fritzler, M. J., Bogdanos, D. P., Meroni, P. L., Roggenbuck, D., Goldman, M., Landegren, N., Bastard, P., Shoenfeld, Y., & Conrad, K. (2022). Autoantibodies and SARS-CoV-2 infection: The spectrum from association to clinical implication: Report of the 15th Dresden Symposium on Autoantibodies. Autoimmunity Reviews, 21(3), 103012. https://doi.org/10.1016/j.autrev.2021.103012 DOI: https://doi.org/10.1016/j.autrev.2021.103012
9. Dotan, A., Muller, S., Kanduc, D., David, P., Halpert, G., & Shoenfeld, Y. (2021). The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmunity Reviews, 20(4), 102792. https://doi.org/10.1016/j.autrev.2021.102792 DOI: https://doi.org/10.1016/j.autrev.2021.102792
10. Greene, C., Connolly, R., Brennan, D., Laffan, A., O’Keeffe, E., Zaporojan, L., O’Callaghan, J., Thomson, B., Connolly, E., Argue, R., Meaney, J. F. M., Martin-Loeches, I., Long, A., Ní Cheallaigh, C., Conlon, N., Doherty, C. P., & Campbell, M. (2024). Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment. Nature Neuroscience, 27(3), 421–432. https://doi.org/10.1038/s41593-024-01576-9 DOI: https://doi.org/10.1038/s41593-024-01576-9
11. Maldonado-Catala, P., Gouripeddi, R., Schlesinger, N., & Facelli, J. C. (2025). Molecular mimicry impact of the COVID-19 pandemic: Sequence homology between SARS-CoV-2 and autoimmune diseases epitopes. Immunoinformatics, 18, 100050. https://doi.org/10.1016/j.immuno.2025.100050 DOI: https://doi.org/10.1016/j.immuno.2025.100050
12. Verma, A. K., Zheng, J., Meyerholz, D. K., & Perlman, S. (2022). SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways. JCI Insight, 7(24), e160277. https://doi.org/10.1172/jci.insight.160277 DOI: https://doi.org/10.1172/jci.insight.160277
13. Beduleva, L., Fomina, K., Khramova, T., Terentiev, A., Menshikova, D., Terentieva, O., Menshikov, I., Sidorov, A., Makhankova, P., & Abisheva, N. (2025). Autoimmune reactions to ACE2 triggered by SARS-CoV-2 S protein and their histopathological consequences. Scientific Reports, 15, 37315. https://doi.org/10.1038/s41598-025-21304-y DOI: https://doi.org/10.1038/s41598-025-21304-y
14. Niculet, E., Chioncel, V., Elisei, A. M., Miulescu, M., Buzia, O. D., Nwabudike, L. C., Craescu, M., Draganescu, M., Bujoreanu, F., Marinescu, E., Arbune, M., Radaschin, D. S., Bobeica, C., Nechita, A., & Tatu, A. L. (2021). Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade. Experimental and Therapeutic Medicine, 21(3), 263. https://doi.org/10.3892/etm.2021.9693 DOI: https://doi.org/10.3892/etm.2021.9693
15. Jernbom, A. F., Skoglund, L., Pin, E., et al. (2024). Prevalent and persistent new-onset autoantibodies in mild to severe COVID-19. Nature Communications, 15, 8941. https://doi.org/10.1038/s41467-024-53356-5 DOI: https://doi.org/10.1038/s41467-024-53356-5
16. Rojas, M., Rodríguez, Y., Acosta-Ampudia, Y., Monsalve, D. M., Zhu, C., Li, Q. Z., Ramírez-Santana, C., & Anaya, J. M. (2022). Autoimmunity is a hallmark of post-COVID syndrome. Journal of Translational Medicine, 20(1), 129. https://doi.org/10.1186/s12967-022-03328-4 DOI: https://doi.org/10.1186/s12967-022-03328-4
17. Gil, A. M., Barahona-Correa, J., Flórez, J. B., Fernández-Ávila, D. G., & Cucunubá, Z. M. (2025). Risk of new onset of immune-mediated diseases after SARS-CoV-2 infection: A systematic review and meta-analysis. Seminars in Arthritis and Rheumatism, 74, 152805. https://doi.org/10.1016/j.semarthrit.2025.152805 DOI: https://doi.org/10.1016/j.semarthrit.2025.152805
18. Herczeg, V., Muzslay, E., Czipó, D., Terkovics, L., Takács, J., Garai, R., Kovács, F., Luczay, A., Körner, A., & Tóth-Heyn, P. (2025). Increasing prevalence of thyroid autoimmunity in childhood type 1 diabetes in the pre-COVID but not during the COVID era. Frontiers in Endocrinology, 15, 1496155. https://doi.org/10.3389/fendo.2024.1496155 DOI: https://doi.org/10.3389/fendo.2024.1496155
19. Izci Duran, T., Turkmen, E., Dilek, M., Sayarlioglu, H., & Arik, N. (2021). ANCA-associated vasculitis after COVID-19. Rheumatology International, 41(8), 1523–1529. https://doi.org/10.1007/s00296-021-04914-3 DOI: https://doi.org/10.1007/s00296-021-04914-3
20. Capes, A., Bailly, S., Hantson, P., Gerard, L., & Laterre, P.-F. (2020). COVID-19 infection associated with autoimmune hemolytic anemia. Annals of Hematology, 99(7), 1679–1680. https://doi.org/10.1007/s00277-020-04137-9 DOI: https://doi.org/10.1007/s00277-020-04137-9
21. Nune, A., Durkowski, V., Pillay, S. S., Barman, B., Elwell, H., Bora, K., Bilgrami, S., Mahmood, S., Babajan, N., Venkatachalam, S., Ottewell, L., & Manzo, C. (2023). New-onset rheumatic immune-mediated inflammatory diseases following SARS-CoV-2 vaccinations until May 2023: A systematic review. Vaccines, 11(10), 1571. https://doi.org/10.3390/vaccines11101571 DOI: https://doi.org/10.3390/vaccines11101571
22. Wee, L. E., Lim, J. T., Tay, A. T., Chiew, C. J., Ong, B., Lye, D. C. B., Lahiri, M., & Tan, K. B. (2024). Autoimmune sequelae after Delta or Omicron variant SARS-CoV-2 infection in a highly vaccinated cohort. JAMA Network Open, 7(8), e2430983. https://doi.org/10.1001/jamanetworkopen.2024.30983 DOI: https://doi.org/10.1001/jamanetworkopen.2024.30983
23. Tarasco, M. C., Iacomino, N., Mantegazza, R., & Cavalcante, P. (2025). COVID-19, Epstein-Barr virus reactivation and autoimmunity: Casual or causal liaisons? Journal of Microbiology, Immunology and Infection, 58(5), 508–516. https://doi.org/10.1016/j.jmii.2025.03.014 DOI: https://doi.org/10.1016/j.jmii.2025.03.014
24. Phetsouphanh, C., Darley, D. R., Wilson, D. B., Howe, A., Munier, C. M. L., Patel, S. K., Juno, J. A., Burrell, L. M., Kent, S. J., Dore, G. J., Kelleher, A. D., & Matthews, G. V. (2022). Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nature Immunology, 23(2), 210–216. https://doi.org/10.1038/s41590-021-01113-x DOI: https://doi.org/10.1038/s41590-021-01113-x
25. Chen, H.-J., Appelman, B., Willemen, H. L. D. M., Bos, A., Prado, J., Mak, W. A., Keijzer, N., Santos Ribeiro, P. S., Goncalves, S. V., Versteeg, S., Geyer, C. E., Larsen, M., Schüchner, E., Bomers, M. K., Lavell, A. H. A., Charlton, B., Wüst, R., Wiersinga, W. J., van Vugt, M., Vidarsson, G., Eijkelkamp, N., & den Dunnen, J. (2026). Transfer of IgG from long COVID patients induces symptomology in mice. Cell Reports Medicine, 7(4), 102693. https://doi.org/10.1016/j.xcrm.2026.102693 DOI: https://doi.org/10.1016/j.xcrm.2026.102693
26. Visvabharathy, L., Zhu, C., Orban, Z. S., Yarnoff, K., Palacio, N., Jimenez, M., Lim, P. H., Penaloza-MacMaster, P., & Koralnik, I. J. (2023). Autoantibody production is enhanced after mild SARS-CoV-2 infection despite vaccination in individuals with and without long COVID. medRxiv. https://doi.org/10.1101/2023.04.07.23288243 DOI: https://doi.org/10.1101/2023.04.07.23288243
27. DiIorio, M., Kennedy, K., Liew, J. W., Putman, M. S., Sirotich, E., Sattui, S. E., Foster, G., Harrison, C., Larché, M. J., Levine, M., Moni, T. T., Thabane, L., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., & Sparks, J. A. (2022). Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: Results from the COVID-19 Global Rheumatology Alliance Vaccine Survey. RMD Open, 8(2), e002587. https://doi.org/10.1136/rmdopen-2022-002587 DOI: https://doi.org/10.1136/rmdopen-2022-002587
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