Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

Abstract

Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.

Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.

Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m²; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA_1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.

Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.

Trial registration: clinicaltrials.gov NCT04324736.

Keywords: BMI; COVID-19; Death; Diabetes; HbA1c; Hypertension; Mechanical ventilation.

Fig. 1

Study flowchart. ^aTwo patients ruled out for not meeting inclusion criteria were in two categories

Fig. 2

Sex- and age-adjusted ORs for the main outcome and for death, using logistic regression models with degree 2 multiple fractional polynomials. (a, b) OR for BMI for the primary outcome (a; p = 0.0001) and for death (b; p = 0.1488) on day 7 (reference value 20 kg/m²; n = 1117). (c, d) OR for HbA_1c for the primary outcome (c; p = 0.2897) and for death (d; p = 0.9129) on day 7 (reference value 42 mmol/mol; n = 846). (e, f) OR for admission plasma glucose for the primary outcome (e; p = 0.0001) and for death (f; p = 0.0059) on day 7 (reference value 5.55 mmol/l; n = 940). The thick black line gives the OR compared with the reference point, the thin grey lines are the 95% CI, and the red dotted red line (OR = 1) corresponds to a similar risk-level as the reference point