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

Abstract

Aims/hypothesis Diabetes has been recognised as a pejorative prognostic factor in coronavirus disease 2019 . 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/interpretationOur results demonstrate that diabetes status was associated with a deleterious COVID-19 prognosis irrespective of age and comorbidity status. Trial registration ClinicalTrials.gov NCT04324736 Keywords Charlson index . Comorbidity . COVID-19 . Death . Diabetes . Invasive mechanical ventilation . Prognosis Abbreviations AST Aspartate aminotransferase CCi Charlson comorbidity index CKD-EPI Chronic Kidney Disease EPIdemiology collaboration CORONADO Coronavirus SARS-CoV-2 and Diabetes Outcomes COVID-19 Coronavirus disease 2019PG and SH contributed to the work equally and should be regarded as colast authors.

Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort

“…Compared to influenza pneumonia, COVID-19 has a poorer prognosis in patients with metabolic diseases [1] . Diabetes is associated with blunted immune responses and increased risk for infection-related morbidity and mortality [2] , [3] . Accordingly, COVID-19-related hospital and intensive care unit (ICU) admission rates and COVID-19 severity are higher in people with type 2 diabetes (T2D) and people with obesity [2] , [3] , [4] .…”

“…Diabetes is associated with blunted immune responses and increased risk for infection-related morbidity and mortality [2] , [3] . Accordingly, COVID-19-related hospital and intensive care unit (ICU) admission rates and COVID-19 severity are higher in people with type 2 diabetes (T2D) and people with obesity [2] , [3] , [4] . The link between obesity and COVID-19 severity has been consistently demonstrated in several countries [5] .…”

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

“…COVID-19 pandemic has had a large negative impact on both diabetes management [ 8 ] and diabetes-related mortality [ 9 ]. As well, pre-existing diabetes mellitus has been considered a risk factor for increased COVID-19 severity and worse outcomes, including higher mortality, irrespective of age and comorbidity status [ 7 ]. The estimates of diabetes prevalence in those who have died of COVID-19 range from 20 to 30% [ 10 , 11 ].…”

“…The case fatality for COVID-19 has been estimated to be 0.5-1.0% [3,4]. Nevertheless, certain characteristics, including increasing age, male sex, ethnicity, socio-economic deprivation, and comorbidities, have been associated with a higher risk of severe COVID-19 or death [5][6][7].…”

Predictors of mortality and ICU requirement in hospitalized COVID‐19 patients with diabetes: A multicentre study

“…Patients with diabetes mellitus are more susceptible to adverse outcomes of COVID‐19 disease. The prevalence of diabetes was two‐ to three‐fold higher in patients who required intensive care unit supports (ICUs), and they had a higher death rate when compared with patients with less severe form of disease (Cariou et al, 2022; Kastora et al, 2022; Mithal et al, 2021; Zhou et al, 2020). However, people with diabetes also have a high prevalence of co‐morbidities like hypertension, obesity and cardiovascular disease than non‐diabetic people, and these comorbidities are linked to severe disease course and poor outcomes (Bae et al, 2021; Perez et al, 2021).…”