New research to be presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2) shows that people who have had COVID-19 have a lower, rather than higher, risk of subsequent development of type 1 diabetes (T1D). Furthermore, the effect is evident only in people who did not receive the SARS-CoV-2 vaccine. The study is by Carl Villaro Nolsøe and Dr Runa Mortansdottir Nolsöe, North Zealand Hospital, Hillerod, Denmark, and colleagues.
Since the COVID-19 pandemic, there has been much discussion and research into possible connections between SARS-CoV-2 infection and other immune system related conditions. In this new study, the authors examined whether infection with SARS-CoV-2 was associated with later onset of T1D among Danish individuals younger than 30 years.
This nationwide, registry-based nested case-control study included 2,115 individuals diagnosed with T1D before age 30 years between January 1, 2020, and December 31, 2023. Each case was 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. Exposure was defined as a first positive SARS-CoV-2 PCR test between January 1, 2020, and December 31, 2021 (after the omicron variant had begun to spread worldwide, but before it accounted for almost all SARS-CoV-2 infections). Statistical modelling was used to estimate associations.
SARS-CoV-2 infection was associated with a statistically significant 16% reduced risk of subsequent T1D across all variants combined across the whole 4-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 4-year observation period. 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. Then, after a while, the immune system will get back to its normal 'resting' state.
The authors further subdivided the exposure groups (COVID-19 infection "yes/no") into levels reflecting both infection and vaccination status, and 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. In the full study population, irrespective of vaccination status, the reduced risk of subsequent T1D was only statistically significant among females, with a 26% decreased risk of T1D, whereas with males the decreased risk was not statistically significant (and as stated above, 16% for men and women combined). Being in different age groups (0-10 years vs.11-30 years) showed no statistically significant differences in later development of T1D.
The authors say: "SARS-CoV-2 infection was associated with a lower risk of developing T1D in Danish individuals younger than 30 years."
They add: "There is conflicting evidence in the literature. Most previous studies have found no association between SARS-CoV-2 and development of type 1 diabetes apart from a few studies that found an indication of an increased risk of type 1 diabetes. Our new study used Danish high-quality registries with a very high rate of test coverage by PCR and we had complete information on vaccination status. The study is observational in nature which means we cannot definitely say for sure that the reduced risk of type 1 diabetes was caused by SARS-CoV-2 infection, but we hope our study will motivate similar studies in other countries with high testing coverage and detailed high-quality data.
As for vaccination status, the authors say: "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 for vaccinated individuals compared with non-vaccinated individuals."
