Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Axfors, Cathrine; Schmitt, Andreas M.; Janiaud, Perrine; Hooft, Janneke van ’t; Abdo, Ehab Fawzy; Abella, Benjamin S.; Akram, Javed; Amaravadi, Ravi K.; Angus, Derek C.; Arabi, Yaseen M.; Azhar, Shehnoor; Baden, Lindsey R.; Baker, Arthur W.; Belkhir, Leïla; Benfield, Thomas; Berrevoets, Marvin A.H.; Chen, Cheng-Pin; Chen, Tsung-Chia; Cheng, Shu‐Hsing; Cheng, Chien-Yu; Chung, Wei‐Sheng; Cohen, Yehuda Z.; Cowan, Lisa; Dalgård, Olav; Val, Fernando; Lacerda, Marcus Vinícius Guimarães; Melo, Gisely Cardoso de; Derde, Lennie; Dubée, Vincent; Elfakir, Anissa; Gordon, Anthony; Hernández-Cárdenas, Carmen Margarita; Hills, Thomas; Hoepelman, Andy I. M.; Huang, Yi-Wen; Igau, Bruno; Jin, Ronghua; Jurado-Camacho, Felipe; Khan, Khalid S.; Kremsner, Peter G.; Kreuels, Benno; Kuo, Chi‐Tai; Le, Thuy; Lin, Yi‐Chun; Lin, Wu-Pu; Lin, Tse-Hung; Lyngbakken, Magnus Nakrem; McArthur, Colin; McVerry, Bryan J.; Meza-Meneses, Patricia; Monteiro, Wuelton Marcelo; Morpeth, Susan; Mourad, Ahmad; Mulligan, Mark J.; Murthy, Srinivas; Naggie, Susanna; Narayanasamy, Shanti; Nichol, Alistair; Novack, Lewis A.; O’Brien, Sean M.; Okeke, Nwora Lance; Perez, Léna; Pérez‐Padilla, Rogelio; Perrin, Laurent; Remigio-Luna, Arantxa; Rivera-Martinez, Norma E.; Rockhold, Frank; Rodríguez-Llamazares, Sebastián; Rolfe, Robert; Rosa, Rossana; Røsjø, Helge; Sampaio, Vanderson de Souza; Seto, Todd B.; Shahzad, Muhammad; Soliman, Shaimaa; Stout, Jason E.; Thirión-Romero, Ireri; Troxel, Andrea B.; Tseng, Ting-Yu; Turner, Nicholas; Ulrich, Robert J.; Walsh, Stephen R.; Webb, Steve; Weehuizen, Jesper M.; Velinova, Maria; Wong, Hon-Lai; Wrenn, Rebekah; Zampieri, Fernando Godinho; Zhong, Wu; Moher, David; Goodman, Steven N.; Ioannidis, John P. A.; Hemkens, Lars G

doi:10.1038/s41467-021-23559-1

Cited by 12 publications

(6 citation statements)

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“…These drugs are shown to targets explicitly the ACE2 receptor, which prevents the virus from entering the cell membrane by inhibiting interaction with S-protein [168]. Although in vitro and some human clinical studies show promising results, the outcomes of various human clinical trials showed no clear benefit of using these drugs to treat COVID-19 [174][175][176]. Also, the impact of CQs on mitochondrial function are not so intensively investigated, but it has been shown that CQ inhibits mitochondrial respiration, ATP production, and function and whether this influences the treatment is not clear [177,178].…”

Section: Potential Covid-19 Treatments and Role Of Mitochondriamentioning

confidence: 99%

Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

et al. 2021

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The recent emergence of severe acute respiratory syndrome-Corona Virus 2 (SARS-CoV-2) in late 2019 and its spread worldwide caused an acute pandemic of Coronavirus disease 19 (COVID-19). Since then, COVID-19 has been under intense scrutiny as its outbreak led to significant changes in healthcare, social activities, and economic settings worldwide. Although angiotensin-converting enzyme-2 (ACE-2) receptor is shown to be the primary port of SARS-CoV-2 entry in cells, the mechanisms behind the establishment and pathologies of COVID-19 are poorly understood. As recent studies have shown that host mitochondria play an essential role in virus-mediated innate immune response, pathologies, and infection, in this review, we will discuss in detail the entry and progression of SARS-CoV-2 and how mitochondria could play roles in COVID-19 disease. We will also review the potential interactions between SARS-CoV-2 and mitochondria and discuss possible treatments, including whether mitochondria as a potential therapeutic target in COVID-19. Understanding SARS-CoV-2 and mitochondrial interactions mediated virus establishment, inflammation, and other consequences may provide a unique mechanism and conceptual advancement in finding a novel treatment for COVID-19.

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Section: Potential Covid-19 Treatments and Role Of Mitochondriamentioning

confidence: 99%

Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

et al. 2021

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Section: Discussionmentioning

confidence: 99%

“…34 Worse than just misattributed benefit, some flawed studies can lead to adoption of harmful treatments: after showing similar initial promise in small studies with relatively high risk of bias, hydroxychloroquine was in fact associated with increased mortality risk in later meta-analyses. 35,36 With all of the challenges in vetting and synthesizing rapidly evolving trial data even for experienced analysts, it is exponentially more difficult for clinicians inundated with critically ill patients to appraise the volume of trials generated in the past 2 years. In response to the rapidly changing trials landscape, both the Infectious Diseases Society of America 8 and the National Institutes of Health to publish a ''living'' clinical guidelines electronically in near real time, facilitating rapid updates to appraise and synthesize key information from ever-evolving clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Landscape of coronavirus disease 2019 clinical trials: New frontiers and challenges

Halabi

Zhou²,

He³

et al. 2022

Clinical Trials

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Background/Aim The number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic. Our primary goal was to provide a critical review of the landscape of clinical trials designed to address the coronavirus disease 2019 pandemic. Specifically, we were interested in assessing the design of phase II/III and phase III interventional trials. Methods We utilized the ClinicalTrials.gov database to include trials registered between 1 December 2019 and 11 April 2021 to survey the current landscape of clinical trials for coronavirus disease 2019. Variables extracted included: National Clinical Trial number, title, location, sponsor, study type, start date, completion date, gender group, age group, primary outcome, secondary outcome, overall status, and associated references. Results About 57% of studies were interventional, 14.5% were phase III trials, and the majority of the therapeutic trials included hospitalized patients. There were 52 primary composite outcomes and 285 unique interventions spanning 10 drug classes. The outcomes, disease severity, and comparators varied substantially across trials, and the trials were often too small to be definitive. Conclusion These findings are relevant as we strongly advocate for global coordination of efforts through the use of common platforms that enable harmonizing of endpoints, collection of common key variables and clear definition of disease severity to have clinically meaningful results from clinical trials.

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“…Previous reported systematic reviews and meta-analyses evaluated safety of HCQ in COVID-19, and focused only on adverse events, (32) or included just a small portion of these RCTs, (33) or also included unpublished clinical trial. (34) Differently from them, we focused on investigating studies that evaluated mortality as outcome, reported severe adverse events associated to COVID-19.…”

Section: Reporting Biasmentioning

confidence: 99%

Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Moraes¹,

Marra²,

Matos³

et al. 2022

Einstein (São Paulo)

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Objective: We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat COVID-19 patients. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (January 2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine and the Control Group (standard of care or placebo); heterogeneity was assessed using the I 2 and the Cochran´s Q statistic. Results: Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with hydroxychloroquine compared to standard of care or placebo (16.7% versus 18.5%; pooled risk ratio 1.09; 95% confidence interval: 0.99-1.19). Also, the rate of serious adverse effects was similar between both Groups, Hydroxychloroquine and Control (3.7% versus 2.9%; pooled risk ratio 1.22; 95% confidence interval: 0.76-1.96). Conclusion: Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients. Prospero database registration: (www.crd.york.ac.uk/prospero) under number CRD42020197070.

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Author Correction: Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials

Cited by 12 publications

References 0 publications

Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

Roles of host mitochondria in the development of COVID-19 pathology: Could mitochondria be a potential therapeutic target?

Landscape of coronavirus disease 2019 clinical trials: New frontiers and challenges

Hydroxychloroquine for treatment of COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

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