Association between renin-angiotensin-aldosterone system inhibitor treatment, neutrophil-lymphocyte ratio, D-Dimer and clinical severity of COVID-19 in hospitalized patients: a multicenter, observational study.
Adult
Aged
Aldosterone
/ adverse effects
Angiotensin Receptor Antagonists
/ adverse effects
Angiotensin-Converting Enzyme Inhibitors
/ adverse effects
COVID-19
/ diagnosis
COVID-19 Nucleic Acid Testing
Female
Fibrin Fibrinogen Degradation Products
/ analysis
Humans
Hypertension
/ diagnosis
Lymphocytes
Male
Middle Aged
Neutrophils
Polymerase Chain Reaction
Renin-Angiotensin System
Retrospective Studies
SARS-CoV-2
/ genetics
Journal
Journal of human hypertension
ISSN: 1476-5527
Titre abrégé: J Hum Hypertens
Pays: England
ID NLM: 8811625
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
12
06
2020
accepted:
14
08
2020
revised:
10
08
2020
pubmed:
26
8
2020
medline:
28
7
2021
entrez:
26
8
2020
Statut:
ppublish
Résumé
The aim of this study was to investigate the possible relationship between worse clinical outcomes and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in hospitalized COVID-19 patients. A total of 247 adult patients (154 males, 93 females; mean age: 51.3 ± 14.2 years) hospitalized for COVID-19 as confirmed by polymerase chain reaction (PCR) were retrospectively reviewed. Demographic and clinical characteristics and laboratory parameters were analyzed using various statistical modeling. Primary outcomes were defined as the need for intensive care unit (ICU), mechanical ventilation, or occurrence of death. Of the patients, 48 were treated in the ICU with a high flow oxygen/noninvasive mechanical ventilation (NIMV, n = 12) or mechanical ventilation (n = 36). Median length of ICU stay was 13 (range, 7-18) days. Mortality was seen in four of the ICU patients. Other patients were followed in the COVID-19 services for a median of 7 days. There was no significant correlation between the primary outcomes and use of ACEIs/ARBs (frequentist OR = 0.82, 95% confidence interval (CI) 0.29-2.34, p = 0.715 and Bayesian posterior median OR = 0.80, 95% CI 0.31-2.02) and presence of hypertension (frequentist OR = 1.23, 95% CI 0.52-2.92, p = 0.631 and Bayesian posterior median OR = 1.25, 95% CI 0.58-2.60). Neutrophil-to-lymphocyte ratio (NLR) and D-dimer levels were strongly associated with primary outcomes. In conclusion, the presence of hypertension and use of ACEIs/ARBs were not significantly associated with poor primary clinical outcomes; however, NLR and D-dimer levels were strong predictors of clinical worsening.
Identifiants
pubmed: 32839534
doi: 10.1038/s41371-020-00405-3
pii: 10.1038/s41371-020-00405-3
pmc: PMC7444679
doi:
Substances chimiques
Angiotensin Receptor Antagonists
0
Angiotensin-Converting Enzyme Inhibitors
0
Fibrin Fibrinogen Degradation Products
0
fibrin fragment D
0
Aldosterone
4964P6T9RB
Types de publication
Journal Article
Multicenter Study
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
588-597Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature Limited.
Références
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.
doi: 10.1016/S0140-6736(20)30183-5
pubmed: 31986264
pmcid: 7159299
Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China. Summary of a report of 72314 cases from the Chinese centre for Disease Control and Prevention. JAMA. 2020;323:1239–42.
doi: 10.1001/jama.2020.2648
pubmed: 32091533
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382:727–33.
doi: 10.1056/NEJMoa2001017
pubmed: 31978945
pmcid: 7092803
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implication for virus origins and receptor binding. Lancet. 2020;395:565–74.
doi: 10.1016/S0140-6736(20)30251-8
pubmed: 32007145
pmcid: 7159086
World Health Organization. https://www.who.int/dg/speeches/detail/who-director-general-s-remarks-at-the-media-briefing-on-2019-ncov-on-11-february-2020 . Accessed 12 Feb 2020.
WHO Director-General’s opening remarks at the media briefing on COVID-19: 11 March 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 . Accessed 30 Mar 2020.
Published by Statista Research Department. Coronavirus death rate in Italy as of April 9, 2020, by age group. 2020. https://www.statista.com/statistics/1106372/coronavirus-death-rate-by-age-group-italy/ . Accessed 9 Apr 2002.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with Coronavirus Disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020. https://doi.org/10.1001/jamainternmed.2020.0994 .
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323:1061–69. https://doi.org/10.1001/jama.2020.1585 .
doi: 10.1001/jama.2020.1585
pubmed: 32031570
pmcid: 7042881
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.e8. https://doi.org/10.1016/j.cell.2020.02.052 .
doi: 10.1016/j.cell.2020.02.052
pubmed: 32142651
pmcid: 7102627
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8:e21.
doi: 10.1016/S2213-2600(20)30116-8
pubmed: 32171062
pmcid: 7118626
Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17:259–60. https://doi.org/10.1038/s41569-020-0360-5 .
doi: 10.1038/s41569-020-0360-5
pubmed: 32139904
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. China medical treatment expert group for Covid-19. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–20. https://doi.org/10.1056/NEJMoa2002032 .
doi: 10.1056/NEJMoa2002032
pubmed: 32109013
Bozkurt B, Kovacs R, Harrington B. HFSA/ACC/AHA statement addresses concerns Re: using RAAS antagonists in COVID-19. 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 .
de Simone G. Position statement of the ESC council on hypertension on ACE-inhibitors and angiotensin receptor blockers. 2020. https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang .
Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–13.
doi: 10.1016/S0140-6736(20)30211-7
pubmed: 32007143
pmcid: 7135076
Oren O, Kopecky SL, Gluckman TJ, Gersh JG, Blumenthal RS. Coronavirus disease 2019 (COVID-19): epidemiology, clinical spectrum and implications for the cardiovascular clinician. Expert analysis. 2020. https://www.acc.org/latest-in-cardiology/articles/2020/04/06/11/08/covid-19-epidemiology-clinical-spectrum-and-implications-for-the-cv-clinician .
Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, et al. The ACE2/angiotensin-(1-7)/MAS axis of the renin-angiotensin system: focus on angiotensin-(1-7). Physiol Rev. 2018;98:505–53.
doi: 10.1152/physrev.00023.2016
pubmed: 29351514
Guo JUNYI, Huang ZHENG, Lin LI, MD, Jiagao LV. Coronavirus disease 2019 (COVID-19) and Cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J Am Heart Assoc. 2020;9:e016219. https://doi.org/10.1161/JAHA.120.016219 .
doi: 10.1161/JAHA.120.016219
pubmed: 32233755
pmcid: 7428639
Hofmann H, Geier M, Marzi A, Krumbiegel M, Peipp M, Fey GH, et al. Susceptibility to SARS coronavirus S protein-driven infection correlates with expression of angiotensin converting enzyme 2 and infection can be blocked by soluble receptor. Biochem Biophys Res Commun. 2004;319:1216–21.
doi: 10.1016/j.bbrc.2004.05.114
pubmed: 15194496
pmcid: 7111153
Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9.
doi: 10.1038/nm1267
pubmed: 16007097
pmcid: 7095783
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63:364–74.
doi: 10.1007/s11427-020-1643-8
pubmed: 32048163
pmcid: 7088566
Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005;24:1634–43.
doi: 10.1038/sj.emboj.7600640
pubmed: 15791205
pmcid: 1142572
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–3.
doi: 10.1126/science.abb2507
pubmed: 32075877
pmcid: 7164637
Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation. 2005;111:2605–10.
doi: 10.1161/CIRCULATIONAHA.104.510461
pubmed: 15897343
Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension. 2004;43:970–6.
doi: 10.1161/01.HYP.0000124667.34652.1a
pubmed: 15007027
Patel AB, Verma A. COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: What is the evidence? JAMA. 2020. https://doi.org/10.1001/jama.2020.4812 .
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin–angiotensin–aldosterone system inhibitors in patients with Covid-19. N Engl J Med. 2020. https://doi.org/10.1056/NEJMsr2005760 .
Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertension. 2020;38:781–2.
doi: 10.1097/HJH.0000000000002450
Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double-edged sword. Circulation. 2020. https://doi.org/10.1161/CIRCULATIONAHA.120.047049 .
Gu H, Xie Z, Li T, Zhang S, Lai C, Zhu P, et al. Angiotensin-converting enzyme 2 inhibits lung injury induced by respiratory syncytial virus. Sci Rep. 2016;6:19840.
doi: 10.1038/srep19840
pubmed: 26813885
pmcid: 4728398
Losartan for patients with COVID-19 requiring hospitalization. 2009. https://clinicaltrials.gov/ct2/show/NCT0431 .
Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J, et al. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res. 2020. https://doi.org/10.1161/CIRCRESAHA.120.317134 .
Li J, Wang X, Chen J, Zhang H, Deng A. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol. 2020. https://doi.org/10.1001/jamacardio.2020.1624 .
Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin–angiotensine–aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020. https://doi.org/10.1056/NEJMoa2006923 .
Li J, Wang X, Chen J, Zhang H, Deng A. Association of renin–angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for Coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol. 2020;e201624. https://doi.org/10.1001/jamacardio.2020.1624 .
Yan X, Li F, Wang X, Yan J, Zhu F, Tang S, et al. Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: a retrospective cross‐sectional study. J Med Virol. 2020:1–9. https://doi.org/10.1002/jmv.26061 .
Zhang L, Long Y, Xiao H, Yang J, Toulon P, Zhang Z. Use of D-dimer in oral anticoagulation therapy. Int J Lab Hematol. 2018;40:503–7. https://doi.org/10.1111/ijlh.12864 .
doi: 10.1111/ijlh.12864
pubmed: 29806239
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844–7.
doi: 10.1111/jth.14768
pubmed: 32073213
pmcid: 7166509
Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14859 .
Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020. https://doi.org/10.1002/ajh.25829 .