SARS-CoV-2 Infection Linked to 16% Lower Risk of Type 1 Diabetes in Under-30s, Danish Registry Study Finds
核心洞察
A nationwide Danish nested case-control study of 2,115 T1D cases and 10,575 matched controls found SARS-CoV-2 (搜索) infection associated with a statistically significant 16% reduced risk of subsequent type 1 diabetes (搜索).
The protective association was strongest within 31–180 days post-infection (42% lower risk) and was confined to unvaccinated individuals (24% reduced risk), with no significant effect among vaccinated people.
The reduced risk was statistically significant only among females (26% decrease), while no individual viral variant alone showed a significant association.
A new nationwide Danish study suggests that SARS-CoV-2 (搜索) infection may be associated with a lower, rather than higher, risk of subsequently developing type 1 diabetes (搜索) (T1D) in individuals under age 30. The findings, presented at the Annual Meeting of the European Association for the Study of Diabetes (搜索) (EASD) in Milan, Italy (Sept 28 – Oct 2), come from a registry-based nested case-control study led by Carl Villaro Nolsøe and Dr Runa Mortansdottir Nolsöe of North Zealand Hospital (搜索), Hillerod, Denmark, and colleagues.
The research examined whether infection with SARS-CoV-2 (搜索) was associated with later onset of T1D among Danish individuals younger than 30 years. The study included 2,115 individuals diagnosed with T1D before age 30 between January 1, 2020, and December 31, 2023, each matched 1:5 by age and sex to 10,575 diabetes-free controls. Individuals with prior diabetes, autoimmune disease, cancer, or immunomodulatory therapy were excluded.
Key Findings
SARS-CoV-2 (搜索) infection was associated with a statistically significant 16% reduced risk of subsequent T1D across all variants combined over the whole four-year observation period. No individual viral variant alone showed a statistically significant association. A 42% lower risk of developing T1D was observed 31–180 days after COVID-19 infection, whereas no association was found in other time windows post-infection across the four-year observation period.
The reduced risk was statistically significant among females, with a 26% decreased risk of T1D, whereas among males the decreased risk was not statistically significant. Being in different age groups (0–10 years vs. 11–30 years) showed no statistically significant differences in later development of T1D.
Vaccination Status and the Protective Signal
When the authors subdivided exposure groups to reflect both infection and vaccination status, they found that the reduced risk of subsequent T1D was confined to unvaccinated individuals who had had COVID-19, with a 24% reduced risk compared to unvaccinated and uninfected individuals. Estimates among vaccinated individuals were imprecise, with no evidence of interaction by vaccination status.
The authors were unable to investigate the lowered risk in relation to the number and types of SARS-CoV-2 (搜索) vaccination due to a lack of statistical power. Regarding the vaccination finding, they noted: "Among the many reasons are possible, we believe the most likely is that the induction of adaptive immunity by vaccination somehow interferes with the viral activation of regulatory mechanisms that could prevent autoimmunity, meaning there is lower protection against type 1 diabetes (搜索) for vaccinated individuals compared with non-vaccinated individuals."
Study Design and Limitations
Exposure was defined as a first positive SARS-CoV-2 (搜索) PCR test between January 1, 2020, and December 31, 2021, a period during which the index, alpha, and delta viral variants were predominant and the omicron variant had begun to spread worldwide but did not yet account for almost all SARS-CoV-2 infections. New cases of type 1 diabetes (搜索) were assessed until December 2023.
The authors emphasized the strengths of the Danish high-quality registries, including a very high rate of test coverage by PCR and complete information on vaccination status. However, they cautioned that the study is observational in nature, meaning the reduced risk of type 1 diabetes (搜索) cannot be definitively attributed to SARS-CoV-2 (搜索) infection.
"There is conflicting evidence in the literature. Most previous studies have found no association between SARS-CoV-2 (搜索) and development of type 1 diabetes (搜索) apart from a few studies that found an indication of an increased risk of type 1 diabetes," the authors stated. They added: "We hope our study will motivate similar studies in other countries with high testing coverage and detailed high-quality data."
Potential Mechanism
The authors suggest a possible explanation could be that certain viral infections can protect against or suppress autoimmune disease such as T1D by activating deep regulatory balancing mechanisms to prevent the adaptive immune response from attacking itself. After a period, the immune system would return to its normal "resting" state, which may explain why the protective association was observed only in the early post-infection window.