RNA-expression of adrenomedullin (ADM), a peptide hormone with vasodilatory effects and involved in the regulation of the endothelial barrier function, is increased in patients with severe coronavirus disease (COVID-19), according to a study published in Critical Care.
“Previous research found increased ADM plasma levels in patients with sepsis and ADM levels correlated with disease severity and mortality in sepsis. Although severe COVID-19 shares some clinical features of sepsis (e.g., endothelial barrier dysfunction), it is not known whether pathophysiological pathways of COVID-19 resemble those of sepsis,” wrote authors led by Julian Hupf, University Hospital Regensburg, Regensburg, Germany.
The ongoing study, which the authors said is the first to evaluate ADM in context of COVID-19, included 45 adult patients presenting with signs of respiratory infection (cough and/or fever) to the emergency department starting from March 2020. Patients were evaluated by PCR analysis to determine whether they had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Of these patients, 21 were classified as COVID-19-positive (PCR positive for SARS-CoV-2 and signs of respiratory infection), 19 were classified as control (other viral or bacterial respiratory infection), while the remaining 5 who had no evidence of respiratory infection were excluded from the analysis. The mean age of the COVID-19 group and control group was 50 and 56 years, respectively. Meanwhile, the risk of clinical deterioration estimated by NEWS-2 Score was noted to be similar between both groups.
Within the COVID-19 group, six patients were admitted to the ICU (defined as “severe COVID-19”), four required mechanical ventilation during hospital stay and three died due to COVID-19 or its related complications. In contrast, only one patient in the control group died from pneumonia.
The study found that ADM expression was significantly elevated in patients with COVID-19 compared to patients with other respiratory infections despite similar clinical features at admission (mean ADM/GAPDH expression: 0.88 ± 0.45 vs 0.58 ± 0.35; P = 0.025). Further, within the COVID-19 group, ADM expression was significantly higher in patients with severe COVID-19 than in patients with less severe COVID-19.
However, study data showed no significant difference in ADM expression between patients with less severe COVID-19 and patients with other respiratory infections than COVID-19. In addition, ADM was able to differentiate severe from non-severe COVID-19 cases with an AUC of 0.82 according to ROC-analysis (P = 0.024, 95% CI 0.64–1.0).
The authors also noted that a significantly elevated expression of ADM was found in the left ventricular myocardial tissue of patients who died from COVID-19 in contrast to controls which consisted of a combination of left ventricular myocardial tissue of patients who died from other respiratory infections or from patients destined for organ donation, which could ultimately not be performed.
“Our findings suggest a potential role for ADM in severe COVID-19,” the authors wrote, adding that “while ADM might be a therapeutic target in sepsis and septic shock, further research is needed regarding ADM in COVID-19. Further, the diagnostic potential of ADM as a marker for progression to severe COVID-19 at first medical contact should be evaluated.”