Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: the CORONADO initiative.

AIMS/HYPOTHESIS: Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 (COVID-19). Since diabetes is typically a disease of advanced age, it remains unclear whether diabetes remains a COVID-19 risk factor beyond advanced age and associated comorbidities. We designed a cohort study that considered age and comorbidities to address this question. METHODS: The Coronavirus SARS-CoV-2 and Diabetes Outcomes (CORONADO) initiative is a French, multicentric, cohort study of individuals with (exposed) and without diabetes (non-exposed) admitted to hospital with COVID-19, with a 1:1 matching on sex, age (±5 years), centre and admission date (10 March 2020 to 10 April 2020). Comorbidity burden was assessed by calculating the updated Charlson comorbidity index (uCCi). A predefined composite primary endpoint combining death and/or invasive mechanical ventilation (IMV), as well as these two components separately, was assessed within 7 and 28 days following hospital admission. We performed multivariable analyses to compare clinical outcomes between patients with and without diabetes. RESULTS: A total of 2210 pairs of participants (diabetes/no-diabetes) were matched on age (mean±SD 69.4±13.2/69.5±13.2 years) and sex (36.3% women). The uCCi was higher in individuals with diabetes. In unadjusted analysis, the primary composite endpoint occurred more frequently in the diabetes group by day 7 (29.0% vs 21.6% in the no-diabetes group; HR 1.43 [95% CI 1.19, 1.72], p<0.001). After multiple adjustments for age, BMI, uCCi, clinical (time between onset of COVID-19 symptoms and dyspnoea) and biological variables (eGFR, aspartate aminotransferase, white cell count, platelet count, C-reactive protein) on admission to hospital, diabetes remained associated with a higher risk of primary composite endpoint within 7 days (adjusted HR 1.42 [95% CI 1.17, 1.72], p<0.001) and 28 days (adjusted HR 1.30 [95% CI 1.09, 1.55], p=0.003), compared with individuals without diabetes. Using the same adjustment model, diabetes was associated with the risk of IMV, but not with risk of death, within 28 days of admission to hospital. CONCLUSIONS/INTERPRETATION: Our results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. TRIAL REGISTRATION: ClinicalTrials.gov NCT04324736.

Sex disparities in COVID-19 outcomes of inpatients with diabetes: insights from the CORONADO study.

OBJECTIVE: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19. METHODS: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736). RESULTS: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only. CONCLUSIONS: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Diabetes Increases Severe COVID-19 Outcomes Primarily in Younger Adults.

CONTEXT: Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE: To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS: Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS: Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.