Mid-regional proadrenomedullin, C-terminal proendothelin-1 values, and disease course are not different in critically ill SARS-CoV-2 pneumonia patients with obesity

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
Google Scholar
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–62.
Google Scholar
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475–81.
Google Scholar
Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA. 2020;323:1574–81.
Google Scholar
Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. COVID-19 in critically ill patients in the Seattle region – case series. N Engl J Med. 2020;382:2012–22.
Google Scholar
Gupta S, Hayek SS, Wang W, Chan L, Mathews KS, Melamed M, et al. Factors associated with death in critically ill patients with coronavirus disease 2019 in the US. JAMA Intern Med. 2020;180:1436–47.
Google Scholar
Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, et al. High prevalence of obesity in severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity. 2020;28:1195–9.
Google Scholar
Caussy C, Wallet F, Laville M, Disse E. Obesity is associated with severe forms of COVID-19. Obesity. 2020;28:1175.
Google Scholar
Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24:422.
Google Scholar
Kruglikov IL, Scherer PE. The role of adipocytes and adipocyte-like cells in the severity of COVI-19 infections. Obesity. 2020;28:1187–90.
Google Scholar
Kooistra EJ, de Nooijer AH, Claassen WJ, Grondman I, Janssen NAF, Netea MG, et al. A higher BMI is not associated with a different immune response and disease course in critically ill COVID-19 patients. Int J Obes. 2021;45:687–94.
Google Scholar
Wilson DC, Schefold JC, Baldirà J, Spinetti T, Saeed K, Elke G. Andrenomedullin in COVID-19 induced endotheliitis. Crit Care. 2020;24:411.
Google Scholar
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Andermatt R, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395:1417–8.
Google Scholar
Struck J, Tao C, Morgenthaler NG, Bergman A. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides. 2004;25:1369–72.
Google Scholar
Papassotiriou J, Morgenthaler NG, Struck J, Alanso C, Bergmann A. Immunoluminometric assay for measurement of the C-terminal Endothelin-1 precursor fragment in human plasma. Clin Chem. 2006;52:1144–51.
Google Scholar
Temmesfeld-Wollbrück B, Hocke AC, Suttorp N, Hippenstiel S. Adrenomedullin and endothelial barrier function. Thromb Haemost. 2007;98:944–51.
Google Scholar
Temmesfeld-Wollbrück B, Brell B, Dávid I, Dorenberg M, Adolphs J, Schmeck B, et al. Adrenomedullin reduces vascular hyperpermeability and improves survival in rat septic shock. Intensive Care Med. 2007;33:703–10.
Google Scholar
Li Y, Jiang C, Wang X, Zhang Y, Shibahara S, Takahashi K, et al. Andrenomedullin is a novel adipokine: adrenomedullin in adipocytes and adipose tissues. Peptides. 2007;28:1129–43.
Google Scholar
Teder P, Noble P. A cytokine reborn? Endothelin-1 in pulmonary inflammation and fibrosis. Am J Cell and Mol Biol. 2000;23:7–10.
Google Scholar
Weil BR, Westby CM, Van Guilder GP, Greiner JJ, Stauffer BL, DeSouza CA. Enhanced endothelin-1 system activity with overweight and obesity. Am J Physiol Heart Circ Physiol. 2011;301:H689–H695.
Google Scholar
Engin A. Endothelial dysfunction in obesity. Adv Exp Med Biol. 2017;960:345–79.
Google Scholar
Van Oers JAH, Kluiters Y, Bons JAP, de Jongh M, Pouwels S, Ramnarain D, et al. Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-C0V-2 pneumonia: a prospective cohort study. J Crit Care. 2021;66:173–89.
Google Scholar
WHO. Clinical management of COVID-19. May 27. 2020. https://www.who.int/publications/i/item/clinical-management-of-covid-19. Accessed 11 Jan 2021.
World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1–253.
De Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, et al. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009;360:20–31.
Google Scholar
Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 2007;4:e296.
Google Scholar
ARDS Definition Task Force Ranieri VM, Rubensfeld GD, Thompson BT, Ferguson ND, Caldwell E. et al. Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307:2526–33.
Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81.
Google Scholar
Appachi S, Kelly KR, Schauer PR, Kirwan JP, Hazen S, Gupta M, et al. Reduced cardiovascular risk following bariatric surgeries is related to a partial recovery from adiposopathy. Obes Surg. 2011;21:1928–36.
Google Scholar
Fezeu L, Julia C, Henegar A, Bitu J, Hu FB, Grobbee DE, et al. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta-analysis. Obes Rev. 2011;12:653–9.
Google Scholar
Czernichow S, Beeker N, Rives-Lange C, Guerot E, Diehl JL, Katsahian S, et al. Obesity doubles mortality in patients hospitalized for SARS-CoV-2 in Paris hospitals, France: a cohort study on 5795 patients. Obesity. 2020;28:2282–9.
Google Scholar
Garcia de Guadiana-Romualdo L, Calvo Nieves MD, Rodríguez Mulero MD, Calcerrada Alises I, Hernández Olivo M, Trapiello Fernández W, et al. MR-proADM as marker of endotheliitis predicts COVID-19 severity. Eur J Clin Invest. 2021;51:e13511.
Google Scholar
Sozio E, Tascini C, Fabris M, D’Aurizio F, De Carlo C, Graziano E, et al. MR-proADM as prognostic factor of outcome in COVID-19 patients. Sci Rep. 2021;11:5121.
Google Scholar
Montrucchio G, Sales G, Rumbolo F, Palmesino F, Fanelli V, Urbino C, et al. Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: an observational prospective study. PLoS One. 2021;16:e0246771.
Google Scholar
Spoto S, Agro FE, Sambuco F, Travaglino F, Valeriani E, Fogolari M, et al. High value of mid-regional proadrenomedullin in COVID-19: a marker of widespread endothelial damage, disease severity and mortality. J Med Virol. 2020;93:2820–7.
Google Scholar
Gregoriano C, Koch D, Kutz A, Haubitz S, Conen A, Bernasconi L, et al. The vasoactive peptide MR-pro-adrenomedullin in COVID-19 patients: an observational study. Clin Chem Lab Med. 2021;59:995–1004.
Google Scholar
Benedetti L, Spinelli D, Callegari T, Bonometti R, Molinaro E, Novara E, et al. High levels of mid-regional proadrenomedullin in ARDS COVID-19 patients: the experience of a single, Italian center. Eur Rev Med Pharmacol Sci. 2021;25:1743–51.
Google Scholar
Braun N, Hoess C, Kutz A, Christ-Crain M, Thomann R, Henzen C, et al. Obesity paradox in patients with community-acquired pneumonia: is inflammation the missing link? Nutrition. 2017;33:304–10.
Google Scholar
Van Oers J, Krabbe J, Kemna E, Kluiters Y, Vos P, De Lange D, et al. Mid-regional proadrenomedullin and mid-regional proatrial natriuretic peptide clearance predicts poor outcome better than single baseline measurements in critically ill patients with pneumonia: a retrospective cohort study. Cureus. 2021;13:e15285.
Google Scholar
Schetz M, de jong A, Deane AM, Druml W, Hemelaar P, Pelosi P, et al. Obesity in the critically ill: a narrative review. Intensive Care Med. 2019;45:757–69.
Google Scholar
Pepper DJ, Sun J, Welsh J, Cui X, Suffredini AF, Eichacker PQ. Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: a systematic review and meta-analysis. Crit Care. 2016;20:181.
Google Scholar
Ball L, Serpa Neto A, Pelosi P. Obesity and survival in critically ill patients with acute respiratory distress syndrome: a paradox within the paradox. Crit Care. 2017;21:114.
Google Scholar
Aldes PA, Savage PD. The obesity paradox: perception vs knowledge. Mayo Clin Proc. 2010;85:112–4.
Google Scholar
Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V, et al. Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes. 2005;29:1011–29.
Google Scholar
Dana R, Bannay A, Bourst P, Ziegler C, Losser MR, Gibot S, et al. Obesity and mortality in critically ill COVID-19 patients with respiratory failure. Int J Obes. 2021;45:2028–37.
Google Scholar
Pouwels S, Ramnarain D, Aupers E, Rutjes-Weurding L, van Oers J. Obesity may not be associated with 28-day mortality, duration of invasive mechanical ventilation and length of intensive care unit and hospital stay in critically ill patients with severe acute respiratory syndrome coronavirus-2: A retrospective cohort study. Medicina. 2021;57:674.
Google Scholar
Kooistra EJ, Brinkman S, van der Voort PHJ, de Keizer NF, Dongelmans DA, Kox M, et al. Body mass index and mortality in coronavirus disease 2019 and other diseases: a cohort study in 35,506 ICU patients. Crit Care Med. 2022;50:e1–e10.
Google Scholar
Kotsis V, Stabouli S, Papakatsika S, Rizos Z, Parati G. Mechanisms of obesity-induced hypertension. Hypertens Rev. 2010;33:386–93.
Google Scholar
Ouchi N, Parker JL, Lugus JL, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97.
Google Scholar
Vila G, Riedl M, Maier C, Struck J, Morgenthaler NG, Handisurya A, et al. Plasma MR-proADM correlates to BMI and decreases in relation to leptin after gastric bypass surgery. Obesity. 2009;17:1184–8.
Google Scholar
Del RyS, Cabiati M, Bianchi V, Caponi L, Di Cecco P, Marchi B, et al. Mid-regional-pro-adrenomedullin plasma levels are increased in obsess adolescents. Eur J Nutr. 2016;55:1255–60.
Google Scholar
Voors AA, Kremer D, Geven C, Ter Maaten JM, Struck J, Bergmann A, et al. Adrenomedullin in heart failure: pathophysiology and therapeutic application. Eur J Heart Fail. 2019;21:163–71.
Google Scholar
Buendgens L, Yagmur E, Bruensing J, Herbers U, Baeck C, Trautwein C, et al. C-terminal proendothelin-1 (CT-proET-1) is associated with organ failure and predicts mortality in critically ill patients. J Intensive Care. 2017;5:25.
Google Scholar
Suthahar N, Meems LMG, Groothof D, Bakker SJL, Gansevoort RT, van Veldhuisen DJ, et al. Relationship between body mass index, cardiovascular biomarkers and incident heart failure. Eur J Heart Fail. 2021;23:396–402.
Google Scholar
Krintus M, Kozinski M, Braga F, Kubica J, Sypniewska G, Pantegghini M. Plasma midregional proadrenomedullin (MR-proADM) concentrations and their biological determinants in a reference population. Clin Chem Lab Med. 2018;56:1161–8.
Google Scholar
Smith JG, Newton-Cheh C, Hedblad B, Struck J, Morgenthaler NG, Bergmann A, et al. Distribution and correlates of midregional proadrenomedullin in the general population. Clin Chem. 2009;55:1593–5.
Google Scholar
Baretella O, Chung SK, Xu A, Van Houtte PM. Pardoxical lack of increase in endothelin-1 levels in obese mice – possible role of endothelin-B receptors. Acta Pharmacol Sin. 2017;38:1699–1700.
Google Scholar
Griffith GJ, Morris TT, Tudball MJ, Herbert A, Mancano G, Pike L, et al. Collider bias undermines our understanding of COVID-19 disease risk and severity. Nat Commun. 2020;11:5749.
Google Scholar