Type 1 diabetes (T1D) in childhood is a complex autoimmune disease characterized by the destruction of pancreatic islet β-cells, ultimately leading to insulin deficiency. It is widely accepted that the development of autoantibodies against multiple pancreatic islet β-cell proteins precedes clinical T1D.
The susceptibility to early islet autoimmunity is influenced by a combination of genetic factors involved in immunity, islet β-cell function, and responses to viral infections. This susceptibility peaks around one year of age, making children in this age group particularly vulnerable to the development of islet autoantibodies.
The COVID-19 pandemic has introduced new variables into the landscape of infectious exposures during childhood. Recent reports suggest an increased incidence of T1D in various regions during the pandemic, with some studies even indicating an association between T1D incidence and COVID-19 diagnosis.
Given that SARS-CoV-2, the virus responsible for COVID-19, can infect islet β-cells, there is a plausible hypothesis that SARS-CoV-2 infection may contribute to the susceptibility for islet autoimmunity and, subsequently, T1D.
However, until now, no study has successfully linked the timing of SARS-CoV-2 infection to the appearance of islet autoantibodies.
The Primary Oral Insulin Trial (POINT) initiated from 2018 to 2021 offered a unique opportunity to investigate this hypothesis. POINT recruited infants with a genetically defined risk of at least 10% for developing multiple islet autoantibodies, capturing a significant portion of those who will develop T1D during childhood.
The study enrolled infants between 4 and 7 months of age, allowing for longitudinal blood sample collection to detect islet autoantibodies. In this context, researchers were able to explore whether there was a temporal association between SARS-CoV-2 infection and islet autoimmunity in the most susceptible age group for islet autoantibody development.
Antibodies and Infections
The study longitudinally measured antibodies to SARS-CoV-2 and influenza A(H1N1) across the COVID-19 pandemic period in young children with a high genetic risk of T1D.
The findings revealed a noteworthy association between the development of islet autoantibodies concurrent with or shortly after the development of SARS-CoV-2 antibodies, but not with H1N1 antibodies.
This association was most pronounced in children who contracted SARS-CoV-2 before 18 months of age, suggesting that SARS-CoV-2 infections may indeed increase the risk of islet autoimmunity in genetically predisposed young children.
Unique Study Design
The study’s design sets it apart from previous research. It actively recruited and followed up young children for islet autoimmunity during the COVID-19 pandemic. Crucially, this study focused on the age group with the highest susceptibility to islet autoantibodies, allowing for comparisons of incidence and risk both before and during the pandemic.
This approach differs from previous cross-sectional analyses that did not select for genetic susceptibility and focused on older children who might have already developed islet autoantibodies before SARS-CoV-2 infection.
The study’s strengths also lie in its ability to control potential confounders. Other viral infections that could affect the association between a specific infection and autoimmunity were likely reduced during the pandemic. Evidence of this reduction was the significant decrease in the incidence rate of influenza A(H1N1) antibodies in the study participants during 2020 and 2021.
Furthermore, despite the increased risk in children with SARS-CoV-2 antibodies, there was no overall increase in the incidence of islet autoantibodies during the pandemic. This suggests a corresponding reduction in other infectious exposures associated with islet autoantibody risk.
Implications for Future Research
While this study provides important insights into the potential link between SARS-CoV-2 infection and islet autoimmunity in young children with a high genetic risk of T1D, more research is needed to fully understand the mechanisms underlying this association. The age of SARS-CoV-2 infection appears to be a critical factor, with the strongest association observed around the peak age of islet autoantibody risk, approximately 12 months.
The exact mechanisms behind this age-related vulnerability remain speculative, but it may involve the possibility that SARS-CoV-2 can infect islet cells at a vulnerable age of β-cell activity, potentially leading to changes that expose islet β cells to autoreactive T cells in susceptible children.
The study from the POINT trial sheds light on the potential link between SARS-CoV-2 infection and the development of islet autoimmunity in genetically predisposed young children. While further research is necessary to elucidate the underlying mechanisms, these findings underscore the importance of monitoring the long-term effects of SARS-CoV-2 infection on childhood health, particularly in populations at risk for autoimmune diseases like T1D. Understanding these relationships may ultimately inform strategies for preventing or delaying the onset of T1D and other autoimmune disorders in vulnerable populations.
reference link : https://jamanetwork.com/journals/jama/fullarticle/2809621