Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

被引:76
作者
Di Castelnuovo, Augusto [1 ]
Costanzo, Simona [2 ]
Antinori, Andrea [3 ]
Berselli, Nausicaa [4 ]
Blandi, Lorenzo [3 ]
Bruno, Raffaele [6 ,7 ]
Cauda, Roberto [8 ,9 ]
Guaraldi, Giovanni [10 ]
Menicanti, Lorenzo [5 ]
My, Ilaria [11 ]
Parrut, Giustino [9 ]
Patti, Giuseppe [13 ]
Perlini, Stefano [14 ,15 ]
Santilli, Francesca [16 ,17 ]
Signorelli, Carlo [18 ]
Spinoni, Enrico [13 ]
Stefanini, Giulio G. [11 ]
Vergori, Alessandra [19 ]
Ageno, Walter [20 ]
Agodi, Antonella [21 ,22 ]
Aiello, Luca [23 ]
Agostoni, Piergiuseppe [24 ,25 ]
Al Moghazi, Samir [26 ]
Astutot, Marinella [21 ,22 ]
Aucella, Filippo [27 ]
Barbieri, Greta [28 ,29 ]
Bartoloni, Alessandro [30 ]
Bonaccio, Marialaura [2 ]
Bonfanti, Paolo [31 ,32 ]
Cacciatore, Francesco [33 ]
Caiano, Lucia [20 ]
Cannata, Francesco [11 ]
Carrozzi, Laura [29 ,34 ]
Cascio, Antonio [35 ]
Ciccullo, Arturo [8 ]
Cingolani, Antonella [8 ,9 ]
Cipollone, Francesco [16 ,17 ]
Colomba, Claudia [35 ]
Crosta, Francesca [12 ]
Dal Praag, Chiara [36 ]
Danzi, Gian Battista [37 ]
D'Ardes, Damiano [16 ,17 ]
Donati, Katleen de Gaetano [8 ]
Del Giacomo, Paola [8 ]
Di Gennaro, Francesco [38 ]
Di Tano, Giuseppe [37 ]
D'OFFizi, Giampiero [39 ]
Filippini, Tommaso [4 ]
Fusco, Francesco Maria [40 ]
Gentile, Ivan [41 ]
机构
[1] Mediterranea Cardioctr, Naples, Italy
[2] IRCCS Neuromed, Dept Epidemiol & Prevent, Pozzilli, IS, Italy
[3] IRCCS, Natl Inst Infect Dis Spallanzani, UOC Immunodeficienze Virali, Rome, Italy
[4] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neural Sci, Sect Publ Hlth, Modena, Italy
[5] IRCCS Policlin San Donato, San Donato Milanese, Italy
[6] Fdn IRCCS Policlin San Matteo, Div Infect Dis 1, Pavia, Italy
[7] Univ Pavia, Dept Clin Surg Diagnost & Paediat Sci, Pavia, Italy
[8] Fdn Policlin Univ A Gemelli IRCCS, Rome, Italy
[9] Univ Cattolica Sacro Cuore, Dipartimento Sicurezza & Bioet, Sede Roma, Rome, Italy
[10] Univ Modena & Reggio Emilia, Dept Surg, Infect Dis Unit, Modena, Italy
[11] Humanitas Clin & Res Hosp IRCCS, Rozzano Milano, Italy
[12] Azienda Sanitaria Locale AUSL Pescara, Dept Infect Dis, Pescara, Italy
[13] Univ Piemonte Orientale, Maggiore della Carita Hosp, Novara, Italy
[14] IRCCS Policlin San Matteo Fdn, Emergency Dept, Pavia, Italy
[15] Univ Pavia, Dept Internal Med, Pavia, Italy
[16] SS Annunziata Hosp, Dept Med & Aging, Clin Med, Chieti, Italy
[17] Univ G dAnnunzio, Chieti, Italy
[18] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy
[19] Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, HIV AIDS Dept, Rome, Italy
[20] Univ Insubria, Dept Med & Surg, Varese, Italy
[21] Univ Catania, Dept Med & Surg Sci & Adv Technol GF Ingrassia, Catania, Italy
[22] AOU Policlin Vittorio Emanuele, Catania, Italy
[23] Osped Morgagni Pierantoni, UOC Anestesia & Rianimaz, Dipartimento Chirurg Gen, Forli, Italy
[24] Ctr Cardiol Monzino IRCCS, Milan, Italy
[25] Univ Milan, Dept Clin Sci & Community Hlth, Cardiovasc Sect, Milan, Italy
[26] IRCCS, Infez Sistem Immunodepresso, Natl Inst Infect Dis L Spallanzani, Rome, Italy
[27] Fdn IRCCS Casa Sollievo della Sofferenza, Foggia, Italy
[28] Azienda Osped Univ Pisana, Dept Clin & Expt Med, Pisa, Italy
[29] Univ Pisa, Pisa, Italy
[30] Univ Florence, Dept Expt & Clin Med, Florence, Italy
[31] ASST Monza, Osped San Gerardo, UOC Malattie Infett, Monza, Italy
[32] Univ Milano Bicocca, Sch Med & Surg, Milan, Italy
[33] Univ Naples Federico II, Dept Translat Med Sci, Naples, Italy
[34] Azienda Osped Univ Pisana, Cardiovasc & Thorac Dept, Pisa, Italy
[35] Univ Palermo, Dept Hlth Promot Mother & Child Care Internal Med, Infect & Trop Dis Unit, Palermo, Italy
[36] Univ Hosp Padova, Dept Med DIMED, Clin Med 3, Padua, Italy
[37] Osped Cremona, Dept Cardiol, Cremona, Italy
[38] IRCCS Neuromed, Med Direct, Pozzilli, IS, Italy
[39] IRCCS, Natl Inst Infect Dis L Spallanzani, UOC Malattie Infett Epatol, Rome, Italy
[40] Azienda Osped Colli, Osped Cotugno, UOC Infez Sistem & Immunodepresso, Naples, Italy
[41] Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy
[42] Univ Padua, Dept Cardiol Thorac & Vasc Sci, Resp Pathophysiol Div, Padua, Italy
[43] PO San Giuseppe Moscati, UOC Pneumol, Taranto, Italy
[44] ASST Milano Nord, Osped Edoardo Bassini, Cinisello Balsamo, Italy
[45] EE Osped Reg F Miulli, COVID 19 Unit, Acquaviva Delle Fonti, BA, Italy
[46] ASL Napoli 1 Ctr, PO S Maria di Loreto Nuovo, UOC Med, Naples, Italy
[47] Magna Graecia Univ Catanzaro, Dept Med & Surg Sci, Infect & Trop Dis Unit, Catanzaro, Italy
[48] Univ Pisa, Dipartimento Farm, Pisa, Italy
[49] AOU Policlin Vittorio Emanuele, UO C Malattie Infett & Tropicali, PO San Marco, Catania, Italy
[50] IRCCS, Natl Inst Infect Dis L Spallanzani, UOC Malattie Infett Apparat Resp, Rome, Italy
关键词
Hydroxychloroquine; COVID-19; Disease severity; Mortality; Inflammation; VIRAL-INFECTIONS; CHLOROQUINE; REPLICATION;
D O I
10.1016/j.ejim.2020.08.019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR= 0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 41 条
[21]   Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19 A Living Systematic Review [J].
Hernandez, Adrian V. ;
Roman, Yuani M. ;
Pasupuleti, Vinay ;
Barboza, Joshuan J. ;
White, C. Michael .
ANNALS OF INTERNAL MEDICINE, 2020, 173 (04) :287-+
[22]   Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis [J].
Lagier, Jean-Christophe ;
Million, Matthieu ;
Gautret, Philippe ;
Colson, Philippe ;
Cortaredona, Sebastien ;
Giraud-Gatineau, Audrey ;
Honore, Stephane ;
Gaubert, Jean-Yves ;
Fournier, Pierre-Edouard ;
Tissot-Dupont, Herve ;
Chabriere, Eric ;
Stein, Andreas ;
Deharo, Jean-Claude ;
Fenollar, Florence ;
Rolain, Jean-Marc ;
Obadia, Yolande ;
Jacquier, Alexis ;
La Scola, Bernard ;
Brouqui, Philippe ;
Drancourt, Michel ;
Parola, Philippe ;
Raoult, Didier .
TRAVEL MEDICINE AND INFECTIOUS DISEASE, 2020, 36
[23]   The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease [J].
McGonagle, Dennis ;
Sharif, Kassem ;
O'Regan, Anthony ;
Bridgewood, Charlie .
AUTOIMMUNITY REVIEWS, 2020, 19 (06)
[24]  
Mehra MR, 2020, LANCET, V395, P1820, DOI [10.1016/S0140-6736(20)31324-6, 10.1016/S0140-6736(20)31180-6]
[25]   Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19) [J].
Mercuro, Nicholas J. ;
Yen, Christina F. ;
Shim, David J. ;
Maher, Timothy R. ;
McCoy, Christopher M. ;
Zimetbaum, Peter J. ;
Gold, Howard S. .
JAMA CARDIOLOGY, 2020, 5 (09) :1036-1041
[26]  
Petal Horby, 2020, MEDRXIV, DOI [10.1101/2020.07.15.20151852, DOI 10.1101/2020.07.15.201518522020]
[27]   The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis? [J].
Roldan, Eugenia Quiros ;
Biasiotto, Giorgio ;
Magro, Paola ;
Zanella, Isabella .
PHARMACOLOGICAL RESEARCH, 2020, 158
[28]   Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State [J].
Rosenberg, Eli S. ;
Dufort, Elizabeth M. ;
Udo, Tomoko ;
Wilberschied, Larissa A. ;
Kumar, Jessica ;
Tesoriero, James ;
Weinberg, Patti ;
Kirkwood, James ;
Muse, Alison ;
DeHovitz, Jack ;
Blog, Debra S. ;
Hutton, Brad ;
Holtgrave, David R. ;
Zucker, Howard A. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2020, 323 (24) :2493-2502
[29]  
Rubin DB., 1987, MULTIPLE IMPUTATION
[30]   Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection [J].
Saleh, Moussa ;
Gabriels, James ;
Chang, David ;
Kim, Beom Soo ;
Mansoor, Amtul ;
Mahmood, Eitezaz ;
Makker, Parth ;
Ismail, Haisam ;
Goldner, Bruce ;
Willner, Jonathan ;
Beldner, Stuart ;
Mitra, Raman ;
John, Roy ;
Chinitz, Jason ;
Skipitaris, Nicholas ;
Mountantonakis, Stavros ;
Epstein, Laurence M. .
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2020, 13 (06) :E008662