Older age, CRP portend deaths in COVID-19 patients with diabetes

Older age and elevated levels of the inflammatory marker C-reactive protein (CRP) may predict mortality in COVID-19 patients, particularly if coupled with diabetes, the retrospective ACCREDIT study has shown.

By day 7 of hospitalization for COVID-19, older patients with high CRP had a triple risk of death if they had diabetes. Conversely, HbA1_c and BMI did not predict COVID-19 outcomes.

“Both variables are easily available upon admission to the hospital,” said lead author Dr Daniel Kevin Llanera from the Imperial College London in London, UK at EASD 2021. “This means we can easily identify the patients who will likely require more aggressive interventions early on their hospital stay to try and improve survival.”

Mortality within 7 days

Included in the ACCREDIT study were 1,004 patients with diabetes who were admitted for COVID-19 to seven hospitals in northwest England from January 1 to June 30, 2020. The mean age of the patients was 74.1 years. Nearly 61 percent were male and 45 percent lived in areas classified as the UK’s most deprived.

Overall, 56.2 percent and 49.6 percent had macrovascular and microvascular complications, respectively. Median BMI was 27.6 kg/m².

The primary outcome of death within 7 days of admission occurred in 24 percent of the patients. By day 30, 33 percent had died, which was higher than in previous studies. “This could be due to greater socioeconomic deprivation and older age,” Llanera theorized.

By day 7, nearly 7.5 percent of patients received intensive care; 9.8 percent had to rely on intravenous (IV) insulin infusions.

Insulin protective, CKD ups death risk

On univariate analysis, insulin infusion appeared protective. Patients receiving it were less likely to die vs those who did not receive IV insulin.

Meanwhile, the presence of chronic kidney disease (CKD) in patients <70 years increased the risk of death more than twofold (odds ratio [OR], 2.74), so was type 2 diabetes (OR, 2.52).

The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) were not associated with COVID-19 outcomes, nor were diabetes-related complications.

Predictors of outcome

On multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome (OR, 3.44 for death) at day 7.

Commenting on the study, Dr Simon Heller from the University of Sheffield in Sheffield UK said diabetes alone could have overwhelmed the additional effects of obesity and HbA1_c.

“Other studies had older age as the overwhelming bad prognostic sign among patients with diabetes. Long-term diabetes may also have effects on the immune system.”

Llanera added that patients with diabetic kidney disease (DKD) are in a chronic pro-inflammatory state which may hinder their ability to stave off the virus. “ACE2 receptors, the molecules that facilitate entry of SARS-CoV-2 into the cells, are also upregulated in the kidneys of patients with DKD.  All these could have led to worse overall outcomes.”

However, he couldn’t tell if strict glucose control, or the use of IV insulin, were of benefit in these patients.