Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC

Abstract Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is u...

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Published inImmunoHorizons Vol. 8; no. 8; pp. 577 - 585
Main Authors Visvabharathy, Lavanya, Dalil, Neda, Leonor, Lucia, Zhu, Chengsong, Orban, Zachary S, Jimenez, Millenia, Lim, Patrick H, Penaloza-MacMaster, Pablo, Koralnik, Igor J
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.08.2024
AAI
Subjects
Adult
Aged
Antibodies, Viral - blood
Antibodies, Viral - immunology
Autoantibodies - blood
Autoantibodies - immunology
Autoimmunity - immunology
Breakthrough Infections
Clinical and Translational Immunology
COVID-19 - immunology
Fatigue - immunology
Female
Humans
Male
Middle Aged
SARS-CoV-2 - immunology
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Summary:Abstract Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus– and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.
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Conceptualization: L.V.; investigation: L.V., N.D., L.L., C.Z., Z.S.O., P.H.L., and M.J.; formal analysis: L.V., N.D., L.L., and C.Z.; resources: L.V., P.P.-M.; data curation: L.V.; writing: L.V. with feedback from all authors; supervision: L.V.; project administration: L.V. and I.J.K.; funding acquisition: L.V.
Current address: Department of Surgery, University of Chicago, Chicago, IL.
Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Lavanya Visvabharathy (lavanya.visvabharathy@bsd.uchicago.edu).
ISSN:2573-7732
2573-7732
DOI:10.4049/immunohorizons.2400033