Impact of Obesity and Metabolic Disorders on Severity of COVID-19 and Vaccine-Breakthrough Infections

Metabolic disorders, COVID-19 and vaccine-breakthrough infections. Nature Reviews Endocrinology 2021

© Norbert Stefan/IDM

Obesity and impaired metabolic health are important risk factors for severe COVID-19. Novel data indicate that these risk factors might also promote vaccine-breakthrough SARS-CoV-2 infections in fully vaccinated people. In a ‘Nature Reviews Endocrinology’ “Year in Review” article DZD-Researcher Norbert Stefan summarizes the most important and up-to-date findings about the relationships of obesity, diabetes and cardiovascular diseases with the severity of COVID-19 and SARS-CoV-2 vaccine-breakthrough infections.  

Obesity has now been established as an important determinant of severe COVID-19. Recently published genetic analyses from the large COVID-19 Host Genetics Initiative, applying the Mendelian randomization approach, prove that increased body mass index (BMI) is causally involved in the pathogenesis of the disease.  

Novel data from a very large community-based cohort study from the UK that evaluated data from 6,910,695 patients with a positive SARS-CoV-2 test result, found that a high BMI was associated with adverse COVID-19 outcomes, independently of several other COVID-19 risk factors, including type 2 diabetes mellitus (T2DM). A linearly increased risk of hospital admission or death due to COVID-19 was observed at a BMI >23 kg/m2. Importantly, the risk of severe COVID-19 outcomes related to an elevated BMI was highest in the youngest age groups (20–39 years old) and decreased progressively with increasing age.  

The author also discusses that accelerated immunosenescence (aging of the immune system) may be an important mechanism explaining the relationship of obesity and T2DM, with severe COVID-19. In this respect he highlights novel data, showing that high glucose levels and insulin resistance, which are frequently found in obesity and T2DM, impair adequate function of CD4+ and CD8+ T cell compartments, resulting in reduced protective antiviral immunity. Furthermore, novel data show that insulin resistance may induce increased infection rates of fat cells and, thereby, progression of COVID-19 in people with SARS-CoV-2 infection. 

While vaccination against COVID-19 is highly effective in fighting the COVID-19 pandemic, obesity and/or T2DM may also be involved in immunosenescence related to efficacy of vaccines against SARS-CoV-2. So far, knowledge about this relationship only emerged from few studies. In these studies, among the pre-existing comorbidities, overweight/obesity and T2DM were frequently found in vaccinated patients with severe or critical illness.  

Thus, as COVID-19 might become an endemic (regularly found and very common) disease, the role of obesity and impaired metabolic health in promoting SARS-Cov-2 infections and severity of the disease, needs to be taken very seriously. On the other hand, as obesity and impaired metabolic health are modifiable risk factors, there is hope that adequate prevention and treatment of these diseases may be powerful tools to fight the COVID-19 pandemic.

Stefan N.: Metabolic disorders, COVID-19 and vaccine-breakthrough infections. Nat Rev Endocrinol. 2021,