Association between COVID-19 and New-Onset Autoimmune Diseases: Updated Systematic Review and Meta-Analysis of 97 Million Individuals, 2025, Tzang+

[Chandelier]

Association between COVID-19 and New-Onset Autoimmune Diseases: Updated Systematic Review and Meta-Analysis of 97 Million Individuals

Spoiler: Authors

Tzang, Chih-Chen; Sheng, Henry; Kuo, Vicky Fu-Hsuan; Luo, Chiao-An; Lin, Tzu-An; Lee, Yi-Ting; Huang, Ewen Shengyao; Wu, Pei-Hsun; Tzang, Bor-Show; Hsu, Tsai-Ching

Abstract​

SARS-CoV-2 infection may induce long-term immune dysregulation; however, its contribution to the development of autoimmune disease remains disputed.
We aim to quantify the relative risk of new-onset autoimmune diseases following COVID-19 and its modifiers through a systematic review and meta-analysis of population-based cohort studies.

MEDLINE, Embase, Cochrane Library, and Web of Science were searched to March 31, 2025, for cohort studies comparing individuals with and without confirmed COVID-19.
Random-effects meta-analysis estimated pooled hazard ratios (HRs) with 95% CIs.
Subgroup analyses examined the severity of acute COVID-19, vaccination status, and demographics.
Risk of bias was evaluated with the Newcastle-Ottawa Scale, certainty of evidence with GRADE, and publication bias with funnel plots and Egger’s test.
The review protocol was prospectively registered in PROSPERO (CRD42025646186).
Seventeen cohort studies, including over 250 million person-years, were included. COVID-19 was associated with a 49% increased risk of new-onset autoimmune-related diseases (AIRD; HR = 1.49, 95% CI: 1.21–1.83; p = 0.0002).

Significant associations (p < 0·05) were observed for 17 of 23 outcomes, with the strongest risks in antiphospholipid syndrome (HR = 2·16), ANCA-associated vasculitis (HR = 2·15), mixed connective tissue disease (HR = 2·12), and immune thrombocytopenic purpura (HR = 1·87).
Risk was higher after severe infection (HR = 1.70), but was reduced in vaccinated individuals (HR = 0.56, compared to 1.42 in unvaccinated individuals).
The certainty of evidence was moderate for conditions with large effect sizes, but low overall, reflecting heterogeneity across studies and the non-randomized design of the included studies.

SARS-CoV-2 infection increases the risk of autoimmune diseases, particularly those affecting vascular and connective tissue.
Risk is amplified by severe infection and attenuated by vaccination.
These findings highlight the necessity of vaccination and targeted follow-up in severe COVID survivors.

Web | DOI | PDF | Clinical Reviews in Allergy & Immunology

 

[rvallee]

If true, this would be pretty ironic because a popular argument from the "immunity debt" crowd has been an unhinged "what if not being regularly infected by common pathogens leads to more autoimmune disease?" fear campaign.

The indirect benefits of vaccines continue to be impressive. What a giant self-own it has been for so many professionals to get swayed by imaginary threat of fear of infections being worse than infections.

 

[SNT Gatchaman]

This systematic review and meta-analysis, based on 17 large-scale retrospective cohort studies, offers the highest level of evidence available on the long-term risk of autoimmune-related diseases following SARS-CoV-2 infection. By synthesizing data from diverse cohorts across high-income healthcare systems and integrating both claims and EMR based datasets, this study provides a comprehensive view of various healthcare settings and diagnostic depth.

Although the pooled relative risk indicated a 49% increase among individuals with COVID-19 infection, the absolute risk elevation was modest due to the low baseline incidence. Using a reference rate of 39.8 cases per 100,000 person-years from a large UK cohort, this corresponds to approximately 20 additional cases per 100,000 personyears, yielding a number needed to harm of about 5,000. Moreover, most pooled outcomes were rated as “low” or “very low” certainty under the GRADE framework, underscoring the need for cautious interpretation.

 

[SNT Gatchaman]

The lack of association between COVID-19 and diseases such as SLE or systemic sclerosis likely reflects fundamental differences in disease-specific immune mechanisms. First, variation in host HLA alleles plays a key role in determining who develops autoimmunity after viral infection, and the immune response to SARS-CoV-2 may not activate the same pathways implicated in these conditions. Second, it is possible that SARS-CoV-2 shares limited sequence homology with autoantigen characteristics, reducing the potential for cross-reactive immune activation. Third, COVID-19 primarily induces extrafollicular B-cell activation and transient autoantibody production, whereas the sustained type I interferon and T-cell–mediated responses driving these disorders are seldom induced.