Doctors at Tokyo Medical and Dental University (TMDU) warn that patients with excess abdominal fat are at increased risk of death from COVID-191. These patients could benefit from treatments tailored to their body type.
COVID-19 patients with BMI over 30 have triple the chance of being sick enough to require hospitalization and are more likely to die2. New research out of Japan adds to a growing body of evidence that when it comes to COVID-19, it’s not how much fat a patient has, but the location that matters1. Both treatment with anti-inflammatory drugs and weight-loss could reduce the chances of COVID-19 related organ failure in apple-shaped patients.
Abdominal fat increases the danger of COVID-19
COVID-19 is more dangerous for people with obese BMI who store fat mainly in their abdomen (often described as apple-shaped)1,3,4. In contrast, people with a high BMI who carry their weight on the hips (described as pear-shaped), have fewer complications1. Therefore, understanding links between belly fat and severe COVID-19 could lead to better treatments for patients with a high BMI.
Research published in Proceedings of the National Acadamy of Science found that patients with severe COVID-19 had a higher BMI than patients with mild symptoms1. Doctors divided patients into two categories based on whether they carried more of their fat under their skin (pear-shaped), or more of their fat packed around their internal organs, giving an apple-shaped appearance. They discovered that patients with the most severe cases of COVID-19 were more likely to have an apple-shape than either pear-shape, or a BMI below 30. This link carried through to survival rates, indicating that Apple-shaped, high BMI patients were more likely to die from COVID-19. Medics suspect that this higher death rate is due to run-away immune response, fuelled by fat stored in the abdomen5. As a result, drugs that damp down this immune response could improve survival of apple-shaped COVID-19 patients.
A run-away immune response
The TMDU Scientists showed obese mice with an apple-shaped fat distribution fared far worse than their pear-shaped or lean cohorts. Additionally, they were more likely to suffer from severe COVID-19 symptoms, and more likely to suffer from a deadly immune reaction. High-tech RNA sequencing showed that the Interleukin-6 (IL6) immune pathway was over-activated in the COVID-19 infected apple-shaped mice.
The amount of IL6 protein in the body is proportionate to the amount of visceral fat we have6. In normal circumstances, IL6 helps our bodies heal from wounds and fight off infection. Too much IL6, however, causes chronic inflammation and can trigger the immune system to overreact to infection. This over-reaction by the immune system can turn deadly, overwhelming the body and damaging vital organs7.
Reining-in IL6: A new treatment approach?
Encouragingly, the researchers found treating apple-shaped mice with a drug that blocked IL6 protein, boosted their chances of fighting off COVID-19. The mice were better able to clear the virus without triggering a dangerous immune response. Losing weight, hence reducing the amount of extra IL6 protein, also protected mice from the worst effects of COVID-19 infection1.
This research suggests that Anti-IL6 drugs such as Tocilizumab, could allow hospitals to provide bespoke treatment plans for COVID-19. While pear-shaped patients might not benefit from IL6 blockers, an apple-shaped COVID-19 patient could significantly increase their chances of survival.
Read the paper here at PNAS.org.
1Hosoya T et al. Apple-shaped obesity: A risky soil for cytokine-accelerated severity in COVID-19.Proc Natl Acad Sci. 2023; e2300155120, 120(22) doi: 10.1073/pnas.2300155120
2Singh R et al. Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression. Front. Endocrinol. 2022; 13: 780872. doi:10.3389/fendo.2022.780872
3Chen L et al. Visceral adipose tissue and risk of COVID-19 susceptibility, hospitalization, and severity: A Mendelian randomization study. Front. Public Health. 2022; 10:1023935. doi: 10.3389/fpubh.2022.1023935.
4Huang Y et al. Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabolism. 2020; 113:154378. doi: 10.1016/j.metabol.2020.154378.
5Neeland I et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019 Sep;7(9):715-725. doi: 10.1016/S2213-8587(19)30084-1
6Wueest S & Konrad D. The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism. Am J Physiol Endocrinol Metab. 2020 Sep 1;319(3):E607-E613. doi: 10.1152/ajpendo.00306.2020. Epub 2020 Jul 27.
7Tanaka T et al. IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harb Perspect Biol. 2014; a016295-a016295, 6(10) doi: 10.1101/cshperspect.a016295.