10% of people with diabetes, COVID-19 die within 7 days of hospital admission
The first large study assessing outcomes among people with diabetes hospitalized for COVID-19 shows that 10% of patients died and 20.3% required intubation for mechanical ventilation within 7 days of admission.
“Diabetes complications — not only macrovascular, but also microvascular — are associated with death on day 7 among people with diabetes hospitalized for COVID-19,” Samy Hadjadj, MD, PhD, professor of endocrinology and diabetes at L’institut du Thorax and University Hospital Nantes and associate head of the department of endocrinology, diabetes and nutrition at University of Nantes in France, told Healio. “Social distancing and prevention of infections remain very important for these people. Longer-term research and additional patients would be welcome to strengthen our message from this interim analysis.”
In the study published in Diabetologia, Hadjadj and colleagues analyzed data from 1,317 adults with diabetes hospitalized for COVID-19 across 53 French centers between March 10 and 31 as part of the CORONADO study, an analysis that included all French hospitals volunteering to share data on patients hospitalized with COVID-19 and diabetes (64.9% men; mean age, 70 years; median BMI, 28.4 kg/m²; 88.5% with type 2 diabetes). Researchers observed microvascular complications and macrovascular complications among 46.8% and 40.8% of patients, respectively. The primary composite endpoint was tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Secondary outcomes were death on day 7, tracheal intubation on day 7, admission to ICU and discharge on day 7. Researchers used age- and sex-adjusted logistic regression analysis to assess the association between the primary outcome and death on day 7 with clinical and biological features.
Within the cohort, 267 patients (20.3%) required tracheal intubation for mechanical ventilation, 140 patients (10.6%) died and 237 patients (18%) were discharged on day 7.
In univariate analysis, researchers found that patients who met the composite primary outcome were more likely to be men vs. women (69.1% vs. 63.2%; P = .042) had a higher BMI (median, 29.1 kg/m² vs. 28.1 kg/m²; P = .0009) and were more likely to be prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (61.5% vs. 55.3%; P = .0386) vs. patients who did not meet the primary outcome.
In the age- and sex-adjusted models, only BMI was positively associated with the primary endpoint (OR = 1.28; 95% CI, 1.1-1.47). BMI was not associated with death on day 7, according to researchers.
“In contrast, HbA1c level was neither associated with the primary outcome nor with death on day 7,” the researchers wrote.
In assessed clinical COVID-19 symptoms, only dyspnea was a predictor of the primary outcome (OR = 2.1; 95% CI, 1.31-3.35). In assessing biological parameters, researchers found that lymphocyte count (OR = 0.67; 95% CI, 0.5-0.88), C-reactive protein (OR = 1.93; 95% CI, 1.43-2.59) and aspartate aminotransferase levels (OR = 2.23; 95% CI, 1.7-2.93) were independent predictors of the primary outcome.
“When considering variables prior to admission, our results support no independent association between a severe course of COVID-19 and age, sex, long-term glucose control, chronic complications, hypertension or usual medications, including renin-angiotensin-aldosterone system blockers and DPP-IV inhibitors,” the researchers wrote. “Only BMI turned out to be independently associated with the primary outcome. When considering variables on admission, dyspnea, lymphopenia, and increased aspartate aminotransferase and C-reactive protein levels were independent prognostic factors for severe course of COVID-19.”
Researchers also found that several factors independently predicted risk for death on day 7, including age (OR = 2.48; 95% CI, 1.74-3.53), treated obstructive sleep apnea (OR = 2.8; 95% CI, 1.46-5.38), microvascular complications (OR = 2.14; 95% CI, 1.16-3.94) and macrovascular complications (OR = 2.54; 95% CI, 1.44-4.5).
“The CORONADO study refined the phenotypes of COVID-19 individuals with diabetes admitted to hospital and showed that chronic glycemic control did not impact the immediate severity of COVID-19,” the researchers wrote. “Elderly populations with long-term diabetes with advanced diabetic complications and/or treated obstructive sleep apnea were particularly at risk of early death, and might require specific management to avoid contamination with SARS-CoV-2. BMI also appears as an independent prognostic factor for COVID-19 severity in the population living with diabetes, requiring hospital admission.”
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The investigators found that among 1,317 patients with diabetes and COVID-19 admitted to hospitals across France in March 2020, 29% met a primary combined outcome of tracheal intubation for mechanical ventilation and/or death within 7 days of admission. An additional 10.6% of patients with diabetes died by day 7 of admission.
Interestingly, type of diabetes, age, HbA1c, and the presence of microvascular and macrovascular complications were not associated with an increased likelihood of reaching the primary outcome; and in multivariate analyses, only BMI was positively associated with that outcome. It is perhaps most surprising that HbA1c, a marker of glucose control, and routine treatments for diabetes prior to admission were not associated with more severe disease, as one might expect. The value of the former finding must be interpreted in light of the lack of HbA1c data for 35.7% of the study population.
As seen in previous studies, elevated markers of inflammation, such as C-reactive protein, and lymphocytopenia were associated with worse outcomes. The authors also demonstrated that older age, treated sleep apnea, and the presence of microvascular and macrovascular complications of diabetes were associated with increased risk for death on day 7 of admission.
The authors conclude that older patients with complications of diabetes, as well as a history of treated obstructive sleep apnea, are at high risk for early death, and that all efforts should be made to prevent these individuals from becoming ill with SARS-CoV-2. The connection with BMI, diabetes and more severe illness requires further investigation, as does the authors’ finding that glycemic control prior to admission was not associated with more severe disease. The authors note that there were few patients with type 1 diabetes in the study and that information regarding this important subgroup was limited. Also, while 16.8% of the patients in this study were of African or Caribbean ethnicity, in the United States, we need more information about African-American patients, who are at risk for more severe disease.
In summary, the CORONADO investigators have provided much needed information about which patients develop more severe illness with the novel SARS-CoV-2 coronavirus. Their work has also created more questions, such as the role that glycemic control plays in COVID-19, and the pathophysiologic mechanisms whereby obesity contributes to more severe disease. All of this said, disease prevention remains our best therapeutic intervention.
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