Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis

Abstract

Objective: Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes.

Research design and methods: We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis.

Results: Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity.

Conclusions: In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.

Figure 1

Meta-analysis odds ratios for requirement of supplemental oxygen/noninvasive ventilatory support by BMI category. Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), diabetes (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CIs of the odds ratios were not adjusted for multiple testing and should not be used to infer definitive effects. Data from Norway; Amphia (in the Netherlands); Austria; South Africa; University of California, Los Angeles, California; Cornell University, Ithaca, New York, were not included in this model, because data were either not available for this outcome or all patients received the therapy. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model; MC, medical center.

Figure 2

Meta-analysis odds ratios for invasive mechanical ventilatory support by BMI category. Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), diabetes (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CIs of the odds ratios have not been adjusted for multiple testing and should not be used to infer definitive effects. Data from Amphia (in the Netherlands) were not available for invasive mechanical ventilatory support. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model; US UCLA, University of California, Los Angeles, California.

Figure 3

Meta-analysis odds ratios for in-hospital mortality by BMI category. Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), diabetes (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CIs of the odds ratios were not adjusted for multiple testing and should not be used to infer definitive effects. Data from Guandong Province, China, and Singapore were not available for in-hospital mortality. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model; US UCLA, University of California, Los Angeles, California.

Figure 4

Meta-analysis odds ratios for supplemental oxygen/noninvasive ventilatory support (A), invasive mechanical ventilatory support (B), and in-hospital mortality by BMI category in patients with preexisting diabetes (C). Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CI of the odds ratios have not been adjusted for multiple testing and should not be used to infer definitive effects. Data from New York were not available for this subgroup analysis. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model.

Figure 4

Meta-analysis odds ratios for supplemental oxygen/noninvasive ventilatory support (A), invasive mechanical ventilatory support (B), and in-hospital mortality by BMI category in patients with preexisting diabetes (C). Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CI of the odds ratios have not been adjusted for multiple testing and should not be used to infer definitive effects. Data from New York were not available for this subgroup analysis. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model.

Figure 4

Meta-analysis odds ratios for supplemental oxygen/noninvasive ventilatory support (A), invasive mechanical ventilatory support (B), and in-hospital mortality by BMI category in patients with preexisting diabetes (C). Models were adjusted for age (<65, ≥65 years), sex (male/female), preexisting cardiovascular disease (yes/no), preexisting respiratory conditions (yes/no), and hypertension (yes/no). The reference BMI is in the normal range (i.e., ≥18 to <25). The 95% CI of the odds ratios have not been adjusted for multiple testing and should not be used to infer definitive effects. Data from New York were not available for this subgroup analysis. D+L, DerSimonian and Laird random effects model; FG&V, Franciscus Gasthuis & Vlietland; I-V, inverse-variance weighted fixed effects model.