COVID-19 as a Trigger for Type 1 Diabetes

Wang, Yichen; Guo, Hui; Wang, Gongquan; Zhai, Jiawei; Du, Bing

doi:10.1210/clinem/dgad165

Cited by 19 publications

(10 citation statements)

References 107 publications

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“…Additionally, considering the direct and indirect impact of the virus on pancreatic islets, 18 it is plausible that SARS-CoV2 infection could contribute to the increasing incidence of T1D observed in various clinical and epidemiological studies. 50 However, the role of SARS-CoV-2 in triggering T1D remains a complex challenge, necessitating further research. Moreover, due to this complexity, adherence to a complete vaccination regimen should be strongly suggested.…”

Section: Discussionmentioning

confidence: 99%

“…The proposed hypothesis of molecular mimicry between SARS‐CoV‐2 epitopes and pancreatic islet autoantigens implies a potential link between SARS‐CoV‐2 infection and the development of T1D in susceptible individuals. Additionally, considering the direct and indirect impact of the virus on pancreatic islets, 18 it is plausible that SARS‐CoV2 infection could contribute to the increasing incidence of T1D observed in various clinical and epidemiological studies 50 . However, the role of SARS‐CoV‐2 in triggering T1D remains a complex challenge, necessitating further research.…”

Section: Discussionmentioning

confidence: 99%

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T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Palmieri,

Santamaria,

Cristiani

et al. 2024

Diabetes Metabolism Res

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AimsIndividuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID‐19). Pre‐existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS‐CoV‐2 antigens in unexposed patients with T1D.Materials and methodsPeripheral blood mononuclear cells (PBMCs) were collected from SARS‐CoV‐2 unexposed patients with T1D and healthy control subjects. SARS‐CoV‐2 specific T cells were identified in PBMCs by ex‐vivo interferon (IFN)γ‐ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis.ResultsT1D patients unexposed to SARS‐CoV‐2 exhibited higher rates of virus‐specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT‐8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT‐8 autoantigens.ConclusionsThe increased frequency of SAR‐CoV‐2‐ reactive T cells in T1D patients might protect against severe COVID‐19 and overt infections. These results emphasise the long‐standing association between viral infections and T1D.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Palmieri,

Santamaria,

Cristiani

et al. 2024

Diabetes Metabolism Res

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“… 19 Moreover, disease progression in type 1 diabetes is a more chronic and long-term process than in COVID-19 infection, so drawing a definitive conclusion on whether COVID-19 is capable of causing type 1 diabetes is difficult and will require longer-term observation at a later date. 44 …”

Section: Discussionmentioning

confidence: 99%

Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study

Shi

Zhao

et al. 2023

BMJ Open Diab Res Care

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IntroductionIt has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis.Research design and methodsThe summary statistics of type 1 diabetes were obtained from two published genome-wide association studies of European population, one as a discovery sample including 15 573 cases and 158 408 controls, and the other data as a replication sample consisting of 5913 cases and 8828 controls. We first performed a two-sample MR analysis to evaluate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Then, reverse MR analysis was conducted to determine whether reverse causality exists.ResultsMR analysis results showed that the genetically predicted type 1 diabetes was associated with higher risk of severe COVID-19 (OR=1.073, 95% CI: 1.034 to 1.114, pFDR=1.15×10−3) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, pFDR=1.15×10−3). Analysis of replication dataset showed similar results, namely a positive association between type 1 diabetes and severe COVID-19 (OR=1.055, 95% CI: 1.029 to 1.081, pFDR=1.59×10−4), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, pFDR=3.50×10−4). No causal association was observed between type 1 diabetes and COVID-19 positive, hospitalized COVID-19, the time to the end of COVID-19 symptoms in the colchicine treatment group and placebo treatment group. Reverse MR analysis showed no reverse causality.ConclusionsType 1 diabetes had a causal effect on severe COVID-19 and death after COVID-19 infection. Further mechanistic studies are needed to explore the relationship between type 1 diabetes and COVID-19 infection and prognosis.

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“…Type 1 diabetes typically begins with immune-mediated damage to pancreatic cells, which is triggered by genetic or environmental factors. Viral infections, such as enteroviruses and respiratory viruses, are probably responsible for autoimmunity against β-cells ( 4 , 5 ). Generally, COVID-19 and T2D appear to have a bidirectional relationship; however, the relationship between COVID-19 and T1D remains controversial and multi-faceted ( 6 ).…”

Section: Contextmentioning

confidence: 99%

Type 1 Diabetes and COVID-19: A Literature Review and Possible Management

Kashfi,

Anbardar,

Asadipooya

et al. 2023

Int J Endocrinol Metab

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Context: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection normally damages the respiratory system but might likewise impair endocrine organs’ function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. The onset of type 1 diabetes (T1D) and associated complications, including diabetic ketoacidosis (DKA), hospitalization, and death, are thought to have increased during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Evidence Acquisition: A literature review was conducted using the electronic databases PubMed and Google Scholar. The keywords “T1D, T1DM, Type 1 DM or Type 1 Diabetes”, “Coronavirus, SARS-CoV-2 or COVID-19” were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Results: A total of 25 manuscripts out of 304 identified studies were selected. There were 15 (60%) multicenter or nationwide studies. The data about the incidence rate of T1D, hospitalization, and death are not consistent across countries; however, DKA incidence and severity seem to be higher during the COVID-19 pandemic. The present study’s data collection demonstrated that COVID-19 might or might not increase the incidence of T1D. Nevertheless, it is associated with the higher incidence and severity of DKA in T1D patients. This finding might indicate that antivirals are not fully protective against the endocrine complications of SARS-CoV-2 infection, which promotes the application of an alternative approach. Conclusions: Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.

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COVID-19 as a Trigger for Type 1 Diabetes

Cited by 19 publications

References 107 publications

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

T‐cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study

Type 1 Diabetes and COVID-19: A Literature Review and Possible Management

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