Wilson et al. Critical Care (2020) 24:411 https://doi.org/10.1186/s13054-020-03151-7 LETTER Open Access Adrenomedullin in COVID-19 induced endotheliitis Darius Cameron Wilson1* , Joerg C. Schefold2, Jaume Baldirà3, Thibaud Spinetti2, Kordo Saeed4 and Gunnar Elke5 Despite the exponential growth in research following the during intensive care (ICU) treatment using the stable rapid spread of SARS-CoV-2 and subsequent COVID-19 protein surrogate, mid-regional proadrenomedullin pandemic, the underlying pathophysiological mechanisms (MR-proADM), found that its assessment could accur- in COVID-19 patients remain poorly understood. The in- ately identify disease progression in patients with non- creased incidence of cardiovascular and thromboembolic severe clinical signs and symptoms, safely increase out- complications, immune cell deactivation and sepsis-like patient treatment with decreased readmission rates and multiple organ failure suggests the involvement of mul- no subsequent mortalities [4], and identify patients re- tiple pathways. Accordingly, recent studies have proposed quiring a rapid administration of antibiotics or triage to that virus-induced endothelial dysfunction and damage, the ICU [5]. Despite the low number of severe viral cases resulting in impaired vascular blood flow, coagulation and within each of these studies (between 2.1% [3] and 3.4% leakage, may partially explain the development of organ [4]), similar hypotheses can also be formulated for pa- dysfunction and oedema [1]. Hence, the development of tient populations with COVID-19. endotheliitis may be a prominent, yet partly under recog- The assessment of MR-proADM in future COVID-19 nised, feature of COVID-19 induced critical illness. studies may therefore provide important information Whilst numerous pro-inflammatory cytokines and blood into the pathophysiological mechanisms underlying biomarkers have already been compared in patients with endotheliitis and subsequent organ dysfunction. The different severities of COVID-19 - to date - no study, re- early identification of patients likely to develop severe port or editorial has described the potential role of adre- clinical symptoms requiring subsequent hospitalisation, nomedullin (ADM) during the host response to COVID- as well as the safe discharge of those already hospita- 19. This is surprising, since ADM has been shown to play lised, may be of particular importance in regions where a key role in reducing vascular (hyper) permeability and healthcare systems are used to full capacity. promoting endothelial stability and integrity following se- vere infection [2]. Thus, ADM may also be of interest Abbreviations ADM: Adrenomedullin; ED: Emergency department; ICU: Intensive care unit; within COVID-19 induced endotheliitis. Indeed, a recent MR-proADM: Mid-regional proadrenomedullin; SARS-CoV-2: Severe acute study investigating gene upregulation in patients with sys- respiratory syndrome coronavirus 2; SCLS: Systemic capillary leak syndrome temic capillary leak syndrome (SCLS), characterised by plasma leakage into peripheral tissue and transient epi- Acknowledgements sodes of hypotensive shock and oedema, found that ADM None. was not only one of the most upregulated genes, but that subsequent application to endothelial cells resulted in a Authors’ contributions DCW was the primary author and editor of the manuscript. All authors protective effect on vascular barrier function [3]. critically reviewed and approved the final manuscript. DCW takes Furthermore, recent clinical studies on sepsis patients responsibility for the paper as a whole. upon emergency department (ED) presentation and Funding No funding was received for this communication. * Correspondence: Dwilso52@caledonian.ac.uk 1 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut of Research, Barcelona, Spain Availability of data and materials Full list of author information is available at the end of the article Not applicable © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wilson et al. Critical Care (2020) 24:411 Page 2 of 2 Ethics approval and consent to participate Not applicable Consent for publication Not applicable Competing interests All authors have provided information on potential conflicts of interests directly or indirectly related to the work submitted in the journal’s disclosure forms. All authors reported no conflicts of interest. Author details 1 Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Institut of Research, Barcelona, Spain. 2Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 3Intensive Care Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 4University Hospital Southampton NHS Foundation Trust, Southampton, UK. 5Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Str. 3 Haus R3, 24105 Kiel, Germany. Received: 17 June 2020 Accepted: 3 July 2020 References 1. 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Crit Care. 2019;23:40 https://doi.org/10.1186/s13054-019-2329-5. 5. del Castillo JG, Wilson DC, Clemente-Callejo C, et al. Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission. Crit Care. 2019;23:335 https://doi. org/10.1186/s13054-019-2613-4. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.