European Heart Journal - Cardiovascular Pharmacotherapy CORRESPONDENCE doi:10.1093/ehjcvp/pvaa083 .. patients, who represent the most vulnerable .. previous ARB (45% vs. 45%; P = 0.98), but Inhibitors of the renin– .. .. angiotensin–aldosterone .. group of patients affected by COVID-19 and .. lower in patients with previous ACE-I (31% vs. .. are also most likely treated with RAAS inhibi- .. 49%; P = 0.01). A propensity for being on ACE-I system and COVID-19 in .. .. .. tors within the general population. To investi- .. was calculated using logistic regression, the critically ill elderly patients .. gate special clinical features in COVID-19, the .. covariates were age, body mass index, sex, se- .. .. .. COVIP study (Very old intensive care patients, .. quential organ failure assessment (SOFA) .. VIP network; NCT04321265) is ongoing. .. score, as well as existing comorbidities of Severe acute respiratory syndrome coronavirus .. COVIP prospectively includes patients equal to .. chronic heart failure, ischaemic heart disease, 2 (SARS-CoV-2), the coronavirus that causes .. .. .. or above 70 years of age with proven COVID- .. renal insufficiency, chronic pulmonary disease, COVID-19, uses the membrane-bound form of .. 19 who are admitted to an intensive care unit .. arterial hypertension, and diabetes mellitus the aminopeptidase angiotensin-converting en- .. .. .. (ICU). A total of 244 ICUs in 38 countries are .. (Table 1). The primary endpoint was ICU mor- zyme 2 (ACE2) to enter cells. Since ACE2 is .. registered to participate in COVIP. The primary .. tality. Both univariable (Model 1) and multivari- centrally involved in the regulation of the .. endpoint is death after 30 days. Inclusion crite- .. able (Model 2, propensity score correction) renin–angiotensin–aldosterone system (RAAS), .. .. .. ria are (i) age >_70 years, (ii) ICU admission, and .. logistic regression models were built to evalu- it has been speculated that RAAS inhibitors in- .. (iii) infection with SARS-CoV-2. Furthermore, a .. ate associations with the primary endpoint. fluence clinical courses. Mehta et al.1 found no .. .. .. follow-up will be performed after 3 months to .. Odds ratios (OR, Model 1, Table 1) and association between use of RAAS inhibitors .. assess death and quality of life. The prospective .. adjusted ORs (aOR, Model 2) with respective and likelihood of COVID-19 testing positivity in .. .. .. design aims to create high-quality data about .. 95% confidence intervals (CIs) were calculated. 18 472 patients. Reynolds et al. performed a .. risk factors, comorbidities, pre-existing frailty, .. The univariate association of previous ACE-I study based on data from electronic health .. ICU-treatment including treatment limitations, .. with lower mortality (OR 0.46, 95% CI 0.26– .. .. records (5894 COVID-19 cases), where a .. and the use of experimental drugs in this critic- .. 0.84; P = 0.01; Table 1) remained statistically sig- Bayesian analysis showed no positive associ- .. ally ill patient collective of elderly patients. An .. nificant after propensity score adjustment (aOR ation of RAAS inhibitors with either a positive .. .. .. interim analysis was performed on 7th of May .. 0.32, 95% CI 0.15–0.67; P = 0.002). test result or severe illness.2 Mancia et al.3 also .. with respect to RAAS inhibitor use. .. In conclusion, in a prospective study of elder- found no evidence in a population-based case- .. In total, 324 patients were evaluated .. ly, critically ill and comorbid patients, we do .. .. control study (6272 case-patients) for RAAS .. (Table 1): 157 (48%) were on RAAS inhibitors, .. find a beneficial association of previous ACE-I inhibitors to affect the risk of contracting .. 62 (19%) on angiotensin-converting enzyme .. use with ICU survival. The current data con- .. .. COVID-19. .. inhibitors (ACE-I), and 95 (29%) on angiotensin .. firms the notion that there is either a positive However, although these retrospective stud- .. II receptor blockers (ARB) before disease .. or no effect of RAAS inhibitor use. In addition, ies report essential data, they are of limited use .. onset. Overall ICU mortality was 45% and was .. our data support the current view that continu- .. .. to inform on elderly, comorbid and severely ill . similar between patients with and without ation of RAAS inhibitor use should be Table 1 Patient characteristics in all patients and in survivors and non-survivors, respectively All patients Survivors Non-survivors P-values OR (95% CI) (n 5 324) (n 5 177) (n 5 147) .................................................................................................................................................................................................................... Age 75 (70–93) 74 (70–93) 77 (70–88) <0.0001* — BMI 26.8 (18.3–51.4) 26.9 (18.3–41.5) 26.5 (18.3–51.4) 0.65 — Male/female sex 224/100 (69/31) 116/61 (52/61) 108/39 (48/39) 0.12 1.46 (0.90–2.35) SOFA score 6 (1–17) 5 (2–13) 7 (1–17) <0.0001* — Chronic heart failure 45 (14.1) 20 (11.5) 25 (17.2) 0.14 1.60 (0.85–3.03) Ischaemic heart disease 63 (19.7) 31 (17.8) 32 (22.1) 0.40 1.31 (0.75–2.27) Renal insufficiency 49 (15.2) 18 (10.2) 31 (21.1) 0.007* 2.35 (1.25–4.40)* Pulmonary disease 82 (25.5) 41 (23.3) 41 (28.3) 0.31 1.30 (0.79–2.15) Arterial hypertension 211 (65.1) 115 (65.0) 96 (65.3) 0.95 1.02 (0.64–1.61) Diabetes mellitus 95 (29.4) 48 (27.1) 47 (32.2) 0.32 1.28 (0.79–2.06) ACE-I 62 (19.1) 43 (24.3) 19 (12.9) 0.01* 0.46 (0.26–0.84)* ARB 95 (29.3) 52 (29.4) 43 (29.3) 0.98 0.99 (0.62–1.61) All continuous variables were non-normally distributed, are presented as median (range) and were compared using Mann–Whitney U tests; categorical variables are presented as n (%) and were compared using v2 tests; P-values and Cochran–Mantel–Haenszel estimates are reported, presented as odds ratios (ORs) with 95% confidence intervals (CIs); statistical significance was assumed at P < 0.05 and is indicated by asterisk (*). Published on behalf of the European Society of Cardiology. All rights reserved. V C The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. 2 Correspondence .. recommended.4 In summary, this is the first .. and Risk of Covid-19. N Engl J Med 2020;382: .. Emergency Medicine, Department of Internal prospective multinational study that demon- .. 2441–2448. .. Medicine, Medical University Innsbruck, .. 3. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao .. Anichstraße 35, 6020 Innsbruck, Austria; strates beneficial associations of ACE-I in high- .. G. Renin-angiotensin-aldosterone system blockers .. 4 Department of Intensive Care 1K12IC, Ghent risk COVID-19 patients and thus impact on .. and the risk of Covid-19. N Engl J Med 2020;382: .. daily practice. However, further research evalu- .. 2431–2440. .. University Hospital, Corneel Heymanslaan 10, .. .. 9000 Gent, Belgium; 5Intensive Care Unit, ating potential causality is warranted. .. 4. Danser AHJ, Epstein M, Batlle D. Renin-angiotensin .. General Hospital of Larissa, Tsakalof 1, Larisa .. system blockers and the COVID-19 pandemic. .. 412 21, Greece; 6Mater Misericordiae .. Hypertension 2020;75:1382–1385. .. Acknowledgements .. .. University Hospital, Eccles St, Northside, Dublin .. .. 7, D07 R2WY, Ireland; 7Department of The support of the study in France by .. Christian Jung1*, .. Anaesthesia and Intensive Care, Ålesund Assistance Publique-Hôpitaux de Paris is .. .. .. Raphael Romano Bruno1, .. Hospital, Åsehaugen 5, 6017 Ålesund, Norway; greatly appreciated. .. Bernhard Wernly2, .. 8 Department of Circulation and Medical .. Michael Joannidis3, Sandra Oeyen4, .. Imaging, Norwegian University of Science and Trial registration number: NCT043 .. .. .. Tilemachos Zafeiridis5, Brian Marsh6, .. Technology, Prinsesse Kristinas gate 3, 7030 21265. .. Finn H. Andersen7,8, Rui Moreno9, .. Trondheim, Norway; 9Unidade de Cuidados .. Ana Margarida Fernandes9, .. Intensivos Neurocrı́ticos e Trauma, Hospital de Conflict of interest: none declared. .. .. S~ao José, Centro Hospitalar Universitário de .. Antonio Artigas10, .. .. .. Lisboa Central, Faculdade de Ciências Médicas Bernardo Bollen Pinto11, References .. Joerg Schefold12, Georg Wolff1 , .. de Lisboa, Nova Médical School, R. José .. Malte Kelm1, Dylan W. De Lange13, .. António Serrano, 1150-199 Lisboa, Portugal; 1. Mehta N, Kalra A, Nowacki AS, Anjewierden S, Han .. .. 10 Department of Intensive Care Medicine, Z, Bhat P, Carmona-Rubio AE, Jacob M, Procop .. Bertrand Guidet14, .. CIBER Enfermedades Respiratorias, GW, Harrington S, Milinovich A, Svensson LG, Jehi .. Hans Flaatten15,16, and .. L, Young JB, Chung MK. Association of use of .. Jesper Fjølner17; on behalf of the .. Corporacion Sanitaria Universitaria Parc Tauli, angiotensin-converting enzyme inhibitors and angio- .. .. Autonomous University of Barcelona, Parc .. COVIP study group .. Taulı́, 1, 08208 Sabadell, Spain; 11Department of tensin II receptor blockers with testing positive for .. 1 Department of Cardiology, Pulmonology and .. coronavirus disease 2019 (COVID-19). JAMA Cardiol .. Vascular Medicine, Medical Faculty, Heinrich- .. Acute Medicine, Geneva University Hospitals, 2020;doi: 10.1001/jamacardio.2020.1855. .. .. Rue Gabrielle-Perret-Gentil 4, 1205 Genève, 2. Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, .. Heine-University Duesseldorf, Moorenstraße 5, .. Switzerland; 12Department of Intensive Care Iturrate E, Johnson SB, Hausvater A, Newman J D, .. 40225 Düsseldorf, Germany; 2Department of .. Medicine, Inselspital, Universitätsspital, .. Cardiology, Paracelsus Medical University, .. Berger JS, Bangalore S, Katz SD, Fishman GI, .. .. University of Bern, Freiburgstrasse 18, 3010 Kunichoff D, Chen Y, Ogedegbe G, Hochman JS. .. Müllner Hauptstraße 48, A-5020 Salzburg, .. Bern, Switzerland; 13Department of Intensive Renin-Angiotensin-Aldosterone System Inhibitors . Austria; 3Division of Intensive Care and . Care Medicine, University Medical Center, University Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands; 14Assistance Publique—Hôpitaux de Paris, Hôpital Saint- Antoine, service de réanimation médicale, 184 Rue du Faubourg Saint-Antoine, Paris F-75012, France; 15Department of Clinical Medecine, University of Bergen, Jonas Lies vei 65, 5021 Bergen, Norway; 16Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Jonas Lies vei 65, 5021 Bergen, Norway; and 17Department of Intensive Care, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus N, Denmark *Corresponding author. Tel: 1492118118912, Email: christian.jung@med.uni-duesseldorf.de