Metabolic Healthy Obesity, Vitamin D Status, and Risk of COVID-19

This study assessed the possible roles of metabolic/obesity phenotypes and vitamin D status (as documented in the UK Biobank prospective cohort survey) in increasing COVID-19 severity in a group with a mean age of 67.7 years. Metabolically unhealthy obesity and serum vitamin D levels <25 nmol/L, both individually and combined, were associated with COVID-19 illness severity. Elderly men had a higher risk of COVID-19 hospitalization, confirmed COVID-19 and severe COVID-19 (ICU admission) than elderly women. 

UK Biobank recruited 502,624 participants aged 37-73 years across England, Scotland and Wales between 2006 and 2010.  At baseline, biological measurements were recorded and touch-screen questionnaires were administered according to a standardized protocol. The total UK Biobank sample included in the current analysis was 353,299 adults with a mean age of 67.7±8.1 years. A total of 192,001 subjects (54.4%) were women and a total of 228,314 subjects (64.6%) were ≥65 years old. Almost two-thirds (67%) of adults in England are overweight or obese. Those of the black, and Asian ethnic groups are more severely affected.  

March 16, 2020 until May 31, 2020

• A total of 3,502, 1,082, and 714 cases of COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19 were determined, respectively. The percentage of the elderly was different in the three COVID-19 outcomes being the highest in COVID-19 hospitalization and the lowest in confirmed COVID-19. The percentage of women was lower than men in the three COVID-19 outcomes. 
• Overall, 96,247 (27.2%) participants were defined as having hypertension, 64,375 (18.2%) hypercholesterolemia, 16,585 (4.7%) diabetes, 41,480 (11.7%) MHO, 43,507 (12.3%) MUHO, and 188,888 (53.5%) vitamin D insufficiency.  
• MUHO represented 12.3% of the total population sample, and 21.5%, 18.5%, and 19.8% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19 and severe COVID-19, respectively.  
• Vitamin D insufficiency phenotypes represented 53.5% of the total population sample, and 59.5%, 61.7% and 61.5% of the included subpopulations with COVID-19 hospitalization, confirmed COVID-19, and severe COVID-19, respectively.  
• In multivariate logistic regression, MUHO and vitamin D insufficiency and their combination were significantly associated with COVID-19 illness severity for COVID-19 hospitalization for confirmed COVID-19 OR for severe COVID-19
• Elderly men were prone to have a higher risk of COVID-19 hospitalization, confirmed COVID-19 and severe COVID-19 than elderly women. 

• Causality in the association between metabolic/obesity phenotypes, vitamin D status and the risk of COVID-19 cannot be concluded from a retrospective study such as this one.  
• Unmeasured and uncorrected confounding factors (e.g., other diseases, socioeconomic factors, health disparities, dietary factors) may affect the magnitude of metabolic and vitamin D effects on COVID-19 outcomes.  
• BMI, metabolic or vitamin D status may have changed in a substantial proportion of the study population over the 10+ years since the data was collected. 

Metabolic/obesity phenotypes and vitamin D status were associated with positive COVID-19 disease status in an adult UK population sample. Obesity in combination with metabolic disorders and vitamin D insufficiency may increase the risk of severe illness from COVID-19. Additional research is necessary to confirm if these are risk factors for severe COVID-19 illness and determine whether other factors increase COVID-19 risk.

• Participant data was derived from the UK Biobank prospective cohort study. 
• The metabolic disorders hypertension, hypercholesterolemia  and diabetes were used to define metabolic health. 
• Using BMI categories and metabolic status, participants were classified into six metabolic/obesity phenotypes: 
• Metabolically Healthy Normal Weight (MHNW) defined as BMI 18.5–24.9 kg/m2 and no metabolic disorders; 
• Metabolically Healthy Overweight (MHOW) defined as BMI 25.0–29.9 kg/m2 and no metabolic disorders;  
• Metabolically Healthy Obesity (MHO) defined as BMI ≥ 30.0 kg/m2 and no metabolic disorders,; 
• Metabolically Unhealthy Normal Weight (MUHNW) defined as BMI 18.5–24.9 kg/m2 and at least one metabolic disorder;  
• Metabolically Unhealthy Overweight (MUHOW) defined as BMI 25.0–29.9 kg/m2 and at least one metabolic disorder; and 
• Metabolically Unhealthy Obesity (MUHO) defined as BMI ≥ 30.0 kg/m2 and at least one metabolic disorder. 
• Two criteria were used to describe vitamin D status: vitamin D deficiency (< 25 nmol/L) and vitamin D insufficiency (< 50 nmol/L). 
• Statistical analyses were performed to test whether the addition of metabolic disorders and vitamin D insufficiency increased obesity associations with COVID-19 hospitalization, confirmed COVID-19 and severe COVID-19 (ICU admission). COVID-19  testing and hospitalization data was acquired from Public Health England.

Li S, Cao Z, Yang H, Zhang Y, Xu F, Wang Y. Metabolic Healthy Obesity, Vitamin D Status, and Risk of COVID-19. Aging Dis. 2021;12(1):61-71. Published 2021 Feb 1. doi:10.14336/AD.2020.1108 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801267/