In a recent study published in Communications Biology, a team of scientists investigated how type 2 diabetes and genetic susceptibility to the disease impacted the severity of and mortality risk associated with coronavirus disease 2019 (COVID-19) using data from the United Kingdom (U.K.) Biobank.
Study: Type 2 diabetes and its genetic susceptibility are associated with increased severity and mortality of COVID-19 in UK Biobank. Image Credit: PeopleImages.com - Yuri A/Shutterstock.com
Background
Despite widespread vaccination across the globe, the COVID-19 pandemic continues, albeit in a less virulent form, with new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
SARS-CoV-2 infections have been found to manifest in a wide range of symptoms, from asymptomatic to severe cases involving acute respiratory distress, pneumonia, and death.
A significant number of COVID-19 cases are also known to progress into post-acute COVID-19 syndrome, commonly known as long coronavirus disease (long COVID).
Extensive research also indicates that clinical factors such as age, smoking behavior, and the presence of comorbidities such as type 2 diabetes, obesity, cardiovascular disease, hypertension, and respiratory diseases are risk factors for severe COVID-19.
Genome-wide association studies have also shown that genetic variants linked to increased risk of cardiovascular disease, type 2 diabetes, lung disease, and those involved in immune mechanisms are associated with a higher risk of severe SARS-CoV-2 infections.
About the study
In the present study, the scientists used U.K. Biobank data to investigate whether type 2 diabetes and polygenic risk scores for type 2 diabetes were associated with increased severity of SARS-CoV-2 infections and a higher COVID-19 mortality rate.
Additionally, they examined the effect of vaccinations on this association and evaluated the impact of numerous SARS-CoV-2 variants, including the recently emerged Omicron variants.
The polygenic risk scores for type 2 diabetes from the genome-wide association study summary statistics obtained from the U.K. Biobank were first used to determine the genetic predisposition for type 2 diabetes.
Here, to account for the confounding impact of body mass index (BMI) on type 2 diabetes, the researchers included BMI as a covariate while calculating the type 2 diabetes polygenic risk scores in the genome-wide association study.
Subsequently, they used the proportional odds models to determine whether type 2 diabetes and the genetic predisposition to type 2 diabetes were associated with increased severity of SARS-CoV-2 infections.
They also examined how type 2 diabetes or the genetic risk for type 2 diabetes impacted survival time when the individual was infected with SARS-CoV-2.
Furthermore, the impact on survival time was reexamined with respect to vaccination status and for a wide range of SARS-CoV-2 variants.
Lastly, the researchers also examined whether mortality rates were significantly different between three groups — COVID-19, type 2 diabetes, and genetic predisposition to type 2 diabetes — using a stratified survivor analysis.
Results
The findings indicated that type 2 diabetes, as well as polygenic risk scores for type 2 diabetes, were associated with increased COVID-19 severity. The mortality rate was also found to be higher for individuals with type 2 diabetes or a genetic predisposition to it.
Based on the time of infection, the mortality rate for type 2 diabetes patients infected with SARS-CoV-2 was two to seven times higher than for those who did not have SARS-CoV-2 infections.
The rate of fatalities was also found to be higher for the early SARS-CoV-2 variants, with the fatality risk decreasing across Alpha, EU1, and Delta variants to the Omicron variants.
Furthermore, vaccinated type 2 diabetes patients had a significantly lower risk of severe SARS-CoV-2 infections than non-vaccinated ones.
The association between polygenic risk scores for type 2 diabetes and increased risk of severe COVID-19 also indicates an interplay between the genetic factors underlying type 2 diabetes and COVID-19, providing potential research avenues to explore to understand the novel genetic factors that are linked to severe SARS-CoV-2 infections.
Conclusions
To summarize, the study examined the relationship between type 2 diabetes or the polygenic risk scores for type 2 diabetes and the odds of developing severe COVID-19.
The findings suggested that individuals who have either the genetic predisposition for or have type 2 diabetes are at an increased risk of severe SARS-CoV-2 infections and a higher risk of mortality due to COVID-19.
However, COVID-19 vaccinations were found to decrease the risk of severe COVID-19 and mortality in these groups.
Journal reference:
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Lee, A., Seo, J., Park, S., Cho, Y., Kim, G., Li, J., Liang, L., Park, T., & Chung, W. (2024). Type 2 diabetes and its genetic susceptibility are associated with increased severity and mortality of COVID-19 in UK Biobank. Communications Biology, 7(1), 122. doi: https://doi.org/10.1038/s42003024057991. https://www.nature.com/articles/s42003-024-05799-1