The first study of COVID-19 to specifically analyse the effect of the disease in hospitalised patients with diabetes has found that one in ten patients dies within 7 days of hospital admission, and one in five is intubated and mechanically ventilated by this point. The research is published by Professor Bertrand Cariou and Professor Samy Hadjadj, diabetologists at l'institut du thorax, University Hospital Nantes, INSERM, CNRS, and University of Nantes, France, and colleagues.
The study shows that two thirds (65%) of COVID-19 patients with diabetes admitted to hospital are men, and the average age of all patients is 70 years. Worse blood sugar control did not seem to impact a patient's outcome, however the presence of diabetic complications and increasing age increase the risk of death, and increased BMI is associated with both increased risk of needing mechanical ventilation and with increased risk of death.
The CORONADO study analysed 1,317 patients admitted to 53 French hospitals (public and private) between 10 and 31 March 2020. The majority of hospitalised subjects had type 2 diabetes (89%) while only 3% had type 1 diabetes, with other types of diabetes in the remaining cases. In 3% of cases, diabetes was actually diagnosed during hospitalisation for COVID-19.
Microvascular complications (eye, kidney and nerves) were found in 47% of the subjects in the study, while macrovascular complications (arteries of the heart, brain, legs) were present in 41% of the patients analysed. Across all patients in this study, by day 7 one in five (20.3%) had been intubated and placed on a ventilator in intensive care, and one in 10 (10.3%) had died. A further 18% had been discharged home at this point.
The presence of microvascular or macrovascular complications each more than doubled the risk of death at day 7. Advanced age also substantially increased the risk of death, with the group of patients aged 75 years and more than 14 times more likely to die than younger patients aged under 55 years, while patients 65-74 years old were three times more likely to die than those under 55 years. The presence of the respiratory condition obstructive sleep apnoea almost tripled the risk of death at 7 days, as did the presence of dyspnoea symptoms (shortness of breath).
The study also confirmed that insulin, and indeed all treatments for modifying blood sugar, are not a risk factor for severe forms of COVID-19 and should be continued in patients with diabetes. Encouragingly, there were no deaths in patients under 65 years old with type 1 diabetes, but the authors highlight there were only 39 patients with type 1 diabetes in this study and other work is ongoing to establish the effect of COVID-19 in this specific population.
Increasing BMI raised the risk of reaching the combined primary outcome of the study (intubation/ventilation or death at day 7). Women were 25% less likely to reach the combined primary endpoint than men (a result that had borderline statistical significance). However, when looking at death only, men were not statistically more likely to die at day 7 than women.
The authors say: "The risk factors for severe form of COVID-19 are identical to those found in the general population: age and BMI." They add: "Elderly populations with long-term diabetes with advanced diabetic complications and/or treated obstructive sleep apnoea were particularly at risk of early death, and might require specific management to avoid infection with the novel coronavirus. BMI also appears as an independent prognostic factor for COVID-19 severity in the population living with diabetes requiring hospital admission. The link between obesity and COVID-19 requires further study."
The authors plan to publish further work in the summer detailing outcomes of some 3000 patients with diabetes hospitalised with COVID-19, looking at their status 28 days after admission to hospital. The next study will also make more detailed comparisons of COVID-19 outcomes in patients with and without diabetes.
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, HbA1c, 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.
Authors
Bertrand Cariou, Samy Hadjadj, Matthieu Wargny, Matthieu Pichelin, Abdallah Al-Salameh, Ingrid Allix, Coralie Amadou, Gwénaëlle Arnault, Florence Baudoux, Bernard Bauduceau, Sophie Borot, Muriel Bourgeon-Ghittori, Olivier Bourron, David Boutoille, France Cazenave-Roblot, Claude Chaumeil, Emmanuel Cosson, Sandrine Coudol, Patrice Darmon, Emmanuel Disse, Amélie Ducet-Boiffard, Bénédicte Gaborit, Michael Joubert, Véronique Kerlan, Bruno Laviolle, Lucien Marchand, Laurent Meyer, Louis Potier, Gaëtan Prevost, Jean-Pierre Riveline, René Robert, Pierre-Jean Saulnier, Ariane Sultan, Jean-François Thébaut, Charles Thivolet, Blandine Tramunt, Camille Vatier, Ronan Roussel, Jean-François Gautier, Pierre Gourdy
[link url="https://medicalxpress.com/news/2020-05-covid-patients-diabetes-die-days.html"]Medical Xpress report[/link]
[link url="https://link.springer.com/article/10.1007/s00125-020-05180-x"]Diabetologia abstract[/link]