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      RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

      research-article
      b , a , c , d , e , b , f , g , b , h , e , i , j , k , l , m , i , n , j , o , p , k , l , q , r , s , t , u , v , w , x , y , z , aa , ab , ac , ad , r , s , ae , af , ag , o , f , f , g , o , af , i , k , l , y , m , ah , o , f , ai , ah , aj , ak , al , am , an , ao , ap , i , f , g , ah , ao , v , aq , ar , t , u , t , u , ab , as , at , ai , ap , ao , au , z , z , h , h , av , an , h , aw , p , ax , at , am , ay , ac , al , k , l , az , az , ay , ac , n , n , ak , m , f , ba , aq , m , au , ay , an , d , bb , s , as , b , s , ae , *
      Vascular Pharmacology
      Elsevier Inc.
      angiotensin converting enzyme inhibitors, ACE-I, angiotensin receptor blockers, ARB, sartans, COVID-19, mortality

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          Abstract

          Objective: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies.

          Methods: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting–enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.

          Results: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association.

          Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

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          Most cited references28

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          Is Open Access

          A new coronavirus associated with human respiratory disease in China

          Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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            Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

            There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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              Is Open Access

              Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

              This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).
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                Author and article information

                Journal
                Vascul Pharmacol
                Vascul. Pharmacol
                Vascular Pharmacology
                Elsevier Inc.
                1537-1891
                1879-3649
                28 September 2020
                28 September 2020
                : 106805
                Affiliations
                [a ]Mediterranea Cardiocentro. Napoli., Italy
                [b ]Department of Epidemiology and Prevention. IRCCS Neuromed. Pozzilli (IS)., Italy
                [c ]UOC Immunodeficienze Virali. National Institute for Infectious Diseases “L. Spallanzani”. IRCCS. Roma., Italy
                [d ]Section of Public Health. Department of Biomedical. Metabolic and Neural Sciences. University of Modena and Reggio Emilia. Modena., Italy
                [e ]IRCCS Policlinico San Donato. San Donato Milanese (MI)., Italy
                [f ]Fondazione Policlinico Universitario A. Gemelli IRCCS. Roma., Italy
                [g ]Università Cattolica del Sacro Cuore- Dipartimento di Sicurezza e Bioetica Sede di Roma. Roma., Italy
                [h ]Infectious Disease Unit. Department of Surgical. Medical. Dental and Morphological Sciences. University of Modena and Reggio Emilia. Modena., Italy
                [i ]University of Eastern Piedmont. Maggiore della Carità Hospital. Novara., Italy
                [j ]Department of Internal Medicine. University of Pavia. Pavia., Italy
                [k ]Humanitas Clinical and Research Center – IRCCS . Rozzano (Mi) –, Italy
                [l ]Humanitas University. Department of Biomedical Sciences. Milano., Italy
                [m ]Department of Infectious Disease. Azienda Sanitaria Locale (AUSL) di Pescara. Pescara., Italy
                [n ]Emergency Department. IRCCS Policlinico San Matteo Foundation. Pavia., Italy
                [o ]Department of Medicine and Aging. Clinica Medica. "SS. Annunziata" Hospital and University of Chieti. Chieti., Italy
                [p ]School of Medicine. Vita-Salute San Raffaele University. Milano., Italy
                [q ]HIV/AIDS Department. National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS. Roma., Italy
                [r ]Dipartimento di Scienze Mediche Traslazionali. Università degli studi di Napoli "Federico II". Napoli., Italy
                [s ]Department of Medicine and Surgery. University of Insubria. Varese., Italy
                [t ]Centro Cardiologico Monzino IRCCS. Milano., Italy
                [u ]Department of Clinical Sciences and Community Health. Cardiovascular Section. University of Milano. Milano., Italy
                [v ]UOC. Anestesia e Rianimazione. Dipartimento di Chirurgia Generale Ospedale Morgagni-Pierantoni. Forlì., Italy
                [w ]UOC Infezioni Sistemiche dell'Immunodepresso. National Institute for Infectious Diseases L. Spallanzani. IRCCS. Rome., Italy
                [x ]Department of Civil Environmental and Architectural Engineering. University of Padova. Padova., Italy
                [y ]Fondazione I.R.C.C.S “Casa Sollievo della Sofferenza”. San Giovanni Rotondo. Foggia., Italy
                [z ]Emergency Medicine Unit. University Hospital of Pisa, Department of Surgical. Medical and Molecular Medicine and Critical Care. University of Pisa. Pisa., Italy
                [aa ]Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia". University of Catania., Italy
                [ab ]Department of Experimental and Clinical Medicine. University of Florence and Azienda Ospedaliero-Universitaria Careggi. Firenze., Italy
                [ac ]UOC Malattie Infettive. Ospedale San Gerardo. ASST, Monza. Monza. Italy
                [ad ]School of Medicine and Surgery. University of Milano-Bicocca. Milano., Italy
                [ae ]Cardiovascular and Thoracic Department. Azienda Ospedaliero-Universitaria Pisana and University of Pisa. Pisa., Italy
                [af ]Infectious and Tropical Diseases Unit- Department of Health Promotion. Mother and Child Care. Internal Medicine and Medical Specialties (PROMISE) - University of Palermo. Palermo., Italy
                [ag ]Servizio di Anestesia e Rianimazione II UO Rianimazione Ospedale San Marco. AOU Policlinico-Vittorio Emanuele. Catania., Italy
                [ah ]Department of Cardiology. Ospedale di Cremona. Cremona., Italy
                [ai ]Medical Direction. IRCCS Neuromed. Pozzilli (IS)., Italy
                [aj ]UOC Malattie Infettive-Epatologia. National Institute for Infectious Diseases L. Spallanzani. IRCCS. Roma., Italy
                [ak ]UOC Infezioni Sistemiche e dell’Immunodepresso. Azienda Ospedaliera dei Colli. Ospedale Cotugno. Napoli., Italy
                [al ]Department of Clinical Medicine and Surgery. University of Naples "Federico II". Napoli., Italy
                [am ]Medicina Interna. Ospedale di Ravenna. AUSL della Romagna. Ravenna., Italy
                [an ]Respiratory Pathophysiology Division. Department of Cardiologic. Thoracic and Vascular Sciences. University of Padova. Padova., Italy
                [ao ]COVID-19 Unit. EE Ospedale Regionale F. Miulli. Acquaviva delle Fonti (BA)., Italy
                [ap ]UOC di Pneumologia. P.O. San Giuseppe Moscati. Taranto., Italy
                [aq ]ASST, Milano, Nord - Ospedale Edoardo Bassini Cinisello Balsamo (MI). Italy
                [ar ]U.O. C. Malattie Infettive e Tropicali. P.O. "San Marco". AOU Policlinico-Vittorio Emanuele. Catania., Italy
                [as ]UOC di Medicina - Presidio Ospedaliero S. Maria di Loreto Nuovo. Napoli., Italy
                [at ]Ospedale Santissima Trinità. Cagliari., Italy
                [au ]Infectious and Tropical Diseases Unit. Deparment of Medical and Surgical Sciences “Magna Graecia” University. Catanzaro., Italy
                [av ]Dipartimento di Farmacia. Università di Pisa. Pisa., Italy
                [aw ]UOC Malattie Infettive-Apparato Respiratorio. National Institute for Infectious Diseases “L. Spallanzani”. IRCCS. Roma., Italy
                [ax ]Computer Service. University of Molise. Campobasso., Italy
                [ay ]Clinica Medica 3. Department of Medicine - DIMED. University hospital of Padova. Padova., Italy
                [az ]UOC Pneumologia. Dipartimento di Malattie Apparato Respiratorio e Torace. Ospedale Morgagni-Pierantoni. Forlì., Italy
                [ba ]UOC Malattie Infettive ad Alta Intensità di Cura. National Institute for Infectious Diseases “L. Spallanzani”. IRCCS. Rome., Italy
                [bb ]Department of Epidemiology. Boston University School of Public Health. Boston., USA
                Author notes
                [* ]Corresponding author.
                Article
                S1537-1891(20)30310-4 106805
                10.1016/j.vph.2020.106805
                7521934
                32992048
                6d8d6108-37a2-4cfb-be92-a23e7a5aed49
                © 2020 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 11 August 2020
                : 23 September 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                angiotensin converting enzyme inhibitors,ace-i,angiotensin receptor blockers,arb,sartans,covid-19,mortality

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