The Obesity-COVID-19 Relationship: How Much Do Diabetes and Age Matter?

Background: Obesity and diabetes have been independently linked to COVID-19 severity, but their joint impact has not been extensively investigated. This study examines the joint and mediating role of diabetes and weight in COVID-19 severity and mortality in a large sample of patients treated in a large urban hospital located in Southern California.Methods: A retrospective observational cohort study of patients who tested positive for COVID-19 between March 8, 2020 and January 25, 2021 was implemented. Participants were patients with a diagnosis of SARS-CoV-2 infection who received care within the Cedars-Sinai Health System in Los Angeles, CA. Inclusion criteria required objectively measured height, weight, and diabetic status to be present in the patients’ medical record (N=4224). Univariable and multivariable logistic regression models were used to identify associated risk factors, and a regression causal mediation analysis examined the role of diabetes in the association between obesity and illness severity. All analyses were stratified by age (<65 and ≥65).Findings: Among individuals younger than 65yo, diabetes accounted for 19-30% of the associations between obesity and COVID-19 illness severity. In both age groups, those with both obesity and diabetes had the highest odds of increased disease severity. Among patients 65yo and older, being underweight (BMI <18.5) was a risk factor for mortality regardless of diabetes history.Interpretation: Our findings have clinical implications in documenting which patients may be at elevated risk for hospitalization and adverse outcomes. More in-depth prospective studies are needed to capture how glycemic regulation before and after infection influence prognosis.Funding Statement: This work is supported by the National Cancer Institute (1U54CA260591-01; Cheng/Figueiredo). The manuscript was partially supported by the National Institute on Minority Health and Health Disparities (NIMHD) Obesity Health Disparities Research Center (U54MD0000502; Salvy/Dutton), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; R01HD092483; Salvy/de la Haye) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Eris M. Field Chair in Diabetes Research (P30-DK063491; Goodarzi). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCI, NIMHD, NICHD or NIDDK. Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The CSMC institutional review board approved all protocols for the current study (Proposal # Pro00056865).