COVID-19 outbreak on the seasonality and incidence of pediatric type 1 diabetes mellitus

Abstract

To respond to the recent study by Carmon et al on type 1 diabetes (T1DM) incidence/seasonality pre-coronavirus disease 2019 and peri-coronavirus disease 2019, we highlighted convergent findings from the Lombardy pediatric T1DM data (2017-2023). Carmon et al reported elevated T1DM incidence and lost seasonality in the pandemic first year in Israel, linking respiratory viral disruption to T1DM risk. Our data show a 2020 step-increase in Lombardy pediatric T1DM and stable elevated rates (2020-2023) unrelated to coronavirus disease 2021 vaccines. Combined Israeli-Italian data suggest the pandemic triggered lasting higher pediatric T1DM incidence, potentially via severe acute respiratory syndrome coronavirus 2-mediated beta cell damage or immunological shifts, emphasizing global surveillance needs for pandemic autoimmune disease links.

Key Words: COVID-19; Diabetes onset; Incidence; Type 1 diabetes; Pediatrics

Core Tip: We note convergence between the Israeli study by Carmon et al [elevated pediatric type 1 diabetes (T1DM) incidence, lost seasonality peri-coronavirus disease 2019] and our Lombardy data (a 2020 step-increase in pediatric T1DM, stable elevated rates 2020-2023, vaccine-unrelated). Combined data suggest that the pandemic triggered lasting higher T1DM incidence (likely via severe acute respiratory syndrome coronavirus 2-mediated beta cell/immune changes), stressing global surveillance for pandemic-autoimmune disease links.

TO THE EDITOR

We read with great interest the study by Carmon et al[1] in a recent issue of the World Journal of Diabetes. The authors are to be commended for their robust, nationwide analysis of type 1 diabetes (T1DM) incidence and seasonality in Israel before and during the coronavirus disease 2019 (COVID-19) pandemic. Their key findings, a significant increase in T1DM incidence concurrent with a loss of the typical seasonal pattern during the first year of the pandemic, provide powerful ecological evidence supporting the role of respiratory viruses as environmental triggers in T1DM pathogenesis. The disruption of the normal virome by lockdown measures and the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) created a unique natural experiment, which their study has expertly leveraged.

These findings from Israel strongly resonate with our own research in the Lombardy region of Italy, another early and severe epicenter of the pandemic. In a multicenter study analyzing pediatric T1DM onset from 2017 to 2020, we also identified a significant step-increase in T1DM incidence, beginning in 2020[2]. While we observed a transient decrease in diagnoses during the chaotic first lockdown wave (March to April 2020, accounting for 11.7% of annual diagnoses compared with 14%-17% in previous years), the overall annual incidence was the highest in the 4-year period[2]. Specifically, the estimated incidence proportion of pediatric T1DM was 16/100000 in 2020 compared with 14/100000 in 2019, 11/100000 in 2018, and 12/100000 in 2017, establishing a new, higher baseline. The incidence in 2020 was significantly higher than in 2017 (P = 0.01) and 2018 (P = 0.002)[2].

The convergence of data from two distinct, high-incidence populations strengthens the hypothesis that the pandemic event itself rather than unrelated cyclical trends precipitated this rise. The loss of seasonality reported by Carmon et al[1] provides a compelling potential mechanism for the increased incidence we observed. Furthermore, in a subsequent follow-up study of our Lombardy cohort from 2020 to 2023, we found that this elevated incidence rate remained stable (ranging from 18.68 to 21.08 per 100000) and was not influenced by the rollout or uptake of COVID-19 vaccination[2,3].

Taken together, the Israeli and Italian data paint a cohesive picture: The COVID-19 pandemic appears to have triggered a lasting increase in the baseline incidence of pediatric T1DM, an effect likely mediated by direct SARS-CoV-2 infection or broader immunological shifts. Proposed mechanisms for this include direct viral infection and destruction of pancreatic beta cells, which express SARS-CoV-2 entry receptors, or indirect damage from a powerful inflammatory response and subsequent autoimmune dysregulation through pathways like molecular mimicry[4-6]. The work by Carmon et al[1] is invaluable in highlighting the disruption of viral seasonality as a key piece of this puzzle while our data confirms the persistence of this new, higher incidence and argues against a role for COVID-19 vaccines. These combined findings underscore the critical need for continued global surveillance to monitor the long-term impact of the pandemic on autoimmune diseases.