key: cord-0801027-gyblg0b3
authors: Hupf, Julian; Mustroph, Julian; Hanses, Frank; Evert, Katja; Maier, Lars S.; Jungbauer, Carsten G.
title: RNA-expression of adrenomedullin is increased in patients with severe COVID-19
date: 2020-08-28
journal: Crit Care
DOI: 10.1186/s13054-020-03246-1
sha: 436ad3936697c807ce385a1b1cfa21890314c633
doc_id: 801027
cord_uid: gyblg0b3

nan

gene. The final diagnosis after patient discharge was reviewed by a consultant physician and patients without evidence of respiratory infection were excluded from analysis (n = 5).

Baseline characteristics of the study population are described in Table 1 . The risk of clinical deterioration estimated by NEWS-2 Score [5] did not differ between both groups. Six patients in the COVID-19 group were admitted to the ICU (defined as "severe COVID-19"), four of them required mechanical ventilation during hospital stay and three of them died due to COVID-19 or related complications. In contrast, only one patient in the control group died from pneumonia.

ADM expression was significantly elevated in patients with COVID-19 than other respiratory infections ( Fig. 1a ) despite similar clinical features at admission. In patients with COVID-19, ADM expression was significantly higher in patients with severe COVID-19 than in patients with less severe COVID-19 (Fig. 1b) . Further, ADM expression was not significantly different between patients with less severe COVID-19 and patients with other respiratory infections than COVID-19 (p = n.s.). According to ROCanalysis, ADM was able to differentiate severe from non-severe COVID-19 cases with an AUC of 0.82 (p = 0.024, 95% CI 0.64-1.0).

To strengthen our hypothesis, we analyzed ADM expression in the left ventricular myocardial tissue of patients who were deceased from COVID-19. Infection with SARS-CoV-2 had been verified by PCR in all of these patients. As control, we used 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. We found a significantly elevated expression of ADM in patients who died from COVID-19 in contrast to controls (Fig. 1c) . Values are median ± interquartile range Fig. 1 Adrenomedullin RNA expression in whole blood is significantly increased in patients with COVID-19 versus other respiratory infections ("CTRL") in whole blood (a, Student's t test). Further, ADM is significantly elevated in patients with severe COVID-19 in contrast to moderate disease (b, Student's t test). ADM expression in myocardial tissue is increased in patients, who died from COVID-19, in comparison to controls ("CTRL", c, Mann-Whitney U test). Values are depicted as mean and standard error of the mean Our findings suggest a potential role for ADM in severe COVID-19. 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.

Limitations of this study are the small number of patients included and RNA expression analysis in contrast to direct measurement of ADM levels. This study, however, is the first to show an association between ADM and severity of COVID-19.

Adrenomedullin and Adrenomedullin-targeted therapy as treatment strategies relevant for sepsis

The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection

SARS-CoV-2 and viral sepsis: observations and hypotheses

Adrenomedullin in COVID-19 induced endotheliitis

NEWS) 2: Standardising the assessment of acute-illness severity in the NHS. Updated report of a working party

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Authors' contributions JH and JM contributed equally to this work. JM, JH, and CJ designed the study, gathered and analyzed data, performed statistical analysis, wrote the manuscript, and are responsible for the integrity of the work as a whole. FH and KE gathered data and revised the manuscript for critical intellectual content. LSM analyzed data and revised the manuscript for critical intellectual content. All authors read and approved the final manuscript.

This study was supported by the German Cardiac Society Clinician Scientist program to Julian Mustroph, DFG grant Ma1982/5-1, SFB 1350 TPA6 and the University of Regensburg ReForM C program. Open access funding provided by Projekt DEAL.

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

The study was approved by the ethics committee of the University of Regensburg, Regensburg, Germany. Informed consent was obtained from each individual previous to study inclusion, who participated in the wholeblood RNA expression study.

Not applicable.

The authors declare that they have no competing interests.