Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials.

Methods

In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality.

Results

The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P=0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine.

Conclusions

Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.)

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

0 comments Cited 13449 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

A Novel Coronavirus from Patients with Pneumonia in China, 2019

Na Zhu, Dingyu Zhang, Wenling Wang … (2020)

Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)

0 comments Cited 12704 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.

0 comments Cited 10104 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): N Engl J Med

Journal ID (iso-abbrev): N Engl J Med

Journal ID (publisher-id): nejm

Title: The New England Journal of Medicine

Publisher: Massachusetts Medical Society

ISSN (Print): 0028-4793

ISSN (Electronic): 1533-4406

Publication date (Electronic): 08 October 2020

Electronic Location Identifier: NEJMoa2022926

Affiliations

The affiliations of the members of the writing committee are as follows: the Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine (P.H., J.T., J.A.W., N.J.W.), Nuffield Department of Population Health (M.M., L.L., J.L.B., N.S., J.R.E., E.J., R.H., M.J.L.), the Medical Research Council (MRC) Population Health Research Unit (N.S., J.R.E., R.H., M.J.L.), University of Oxford, the Oxford University Hospitals NHS Foundation Trust (K.J., M.J.L.), and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (M.J.L.), Oxford, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester (M.W.), the Regional Infectious Diseases Unit, North Manchester General Hospital (A.U.), University of Manchester (A.U., T.F.), and Manchester University NHS Foundation Trust (T.F.), Manchester, the Research and Development Department, Northampton General Hospital, Northampton (E.E.), the Department of Respiratory Medicine, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees (B.P.), University Hospitals Birmingham NHS Foundation Trust and Institute of Microbiology and Infection, University of Birmingham, Birmingham (T.W.), James Cook University Hospital, Middlesbrough (J.W.), North West Anglia NHS Foundation Trust, Peterborough (J.F.), the Department of Infectious Diseases, Cardiff and Vale University Health Board, and the Division of Infection and Immunity, Cardiff University, Cardiff (J.U.), Roslin Institute, University of Edinburgh, Edinburgh (J.K.B.), the School of Life Course Sciences, King’s College London (L.C.C.), and the Intensive Care National Audit and Research Centre (K.R.), London, the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton (S.N.F.), the Department of Mathematics and Statistics, Lancaster University, Lancaster (T.J.), the MRC Biostatistics Unit, University of Cambridge, Cambridge (T.J.), and the Respiratory Medicine Department, Nottingham University Hospitals NHS Trust (W.S.L.), and the School of Medicine, University of Nottingham (A.M., E.J.), Nottingham — all in the United Kingdom; and the Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand (J.T., J.A.W., N.J.W.).

Author notes

Address reprint requests to Dr. Horby or Dr. Landray at the RECOVERY Central Coordinating Office, Richard Doll Bldg., Old Road Campus, Roosevelt Dr., Oxford OX3 7LF, United Kingdom, or at recoverytrial@ 123456ndph.ox.ac.uk .

[*]

A complete list of collaborators in the RECOVERY trial is provided in the Supplementary Appendix, available at NEJM.org.

Drs. Horby, Mafham, and Linsell and Prof. Juszczak, Dr. Haynes, and Dr. Landray contributed equally to this article.

Article

Publisher ID: NJ202010083832101

DOI: 10.1056/NEJMoa2022926

PMC ID: 7556338

PubMed ID: 33031652

SO-VID: 82979fd7-e8ac-42a5-a5db-c60782d0b21f

License:

This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections.

History

Funding

Funded by: National Institute for Health Research, FundRef http://dx.doi.org/10.13039/501100000272;

Award ID: MC_PC_19056

Funded by: UK Research and Innovation, FundRef http://dx.doi.org/10.13039/100014013;

Award ID: MC_PC_19056

Custom metadata

release-date-display-string 2020-10-08T17:00:00-04:00

release-date-year 2020

release-date-month 10

release-date-day 08

release-date-hour 17

release-date-minute 00

release-date-second 00

release-date-time-zone -04:00

Data availability:

Comments

Comment on this article

scite_

Cited by 550

See all cited by

- Version 1
- Version 1

Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

UCL: Covid-19 Research

Most cited references 36

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

A Novel Coronavirus from Patients with Pneumonia in China, 2019

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Author and article information

Journal

Affiliations

Author notes

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 554

Cited by 550