Abstract: www.nature.com/scientificreports OPEN Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States Wataru Ando1,5*, Takeshi Horii2,5, Takayuki Uematsu3, Hideaki Hanaki4, Koichiro Atsuda2 & Katsuya Otori1 The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0–4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470–34.600] and 55.803 [12.761–244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients. Coronavirus disease (COVID-19) is currently one of the most concerning infections ­globally1. It has a high incidence and mortality rate in the United ­States2. The risk of increasing COVID-19 severity has been reported, with men having a 2.76-fold higher risk of hospitalization owing to COVID-19 than women. According to Grasselli et al.3, 82% of patients admitted to intensive care units (ICUs) were men. Obesity was reported to increase the risk of COVID-19, ICU admission, and death by 1.46-, 2.13-, and 1.74-fold, respectively, suggesting that obesity may affect lung function and immune ­function4. Furthermore, the greatest risk of severe COVID-19 is ­age1. Additionally, statistical analyses by the Center for Disease Control reported an increase in COVID-19 risk with an increase in age; compared with the 18–29-year-old group, the 85-year-old group had a 13- and 630-fold increase in hospitalization and mortality risks, respectively. Therefore, patient characteristics, such as male sex, obesity, and advanced age, can be risk factors for severe d ­ isease5. Studies reported that COVID-19 comorbidities, including hypertension, chronic heart disease, lung d ­ isease6, and type 2 diabetes (T2D), remarkably affected disease ­severity7. T2D is a serious social problem in the United ­States8 because the number of newly diagnosed patients with T2D increased by 75% for all age groups between 1988 and 2­ 0109. Moreover, less than half of all American adults do not follow the recommended guidelines for diabetes ­care10, and obese men aged > 60 years are more likely to develop ­T2D11,12. Therefore, risk factors for T2D are considered similar to those for severe COVID-19. Although several reports exist on the risk of severe COVID-19, studies on severe COVID-19 owing to overlapping risk 1 Department of Clinical Pharmacy, Center for Clinical Pharmacy and Sciences, Kitasato University School of Pharmacy,..