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Systematic Review
Andrew Hill, Ahmed Abdulamir, Sabeena Ahmed, Asma Asghar, Olufemi Emmanuel Babalola, Rabia Basri, Carlos Chaccour, Aijaz Zeeshan Khan Chachar, Abu Tauib Mohammed Chowdhury, Ahmed Elgazzar, Leah Ellis, Jonathan Falconer, Anna Garratt, Basma Hany, Hashim A Hashim, Wasim Ul Haque, Arshad Hayat, Shuixiang He, Ramin Jamshidian, Wasif Ali Khan, Ravi Kirti, Alejandro Krolewiecki, Carlos Lanusse, Jacob Levi, Reaz Mahmud, Sermand Ahmed Mangat, Kaitlyn McCann, Anant Mohan, Mortezza Shakshi Niaee, Nurullah Okumus, Victoria Pilkington, Chinmay Saha Podder, Ambar Qavi, Houssam Raad, Mohammaed Sadegh Rezai, Surapaneni Sasank, Veerapaneni Spoorthi, Tejas Suri, Junzheng Wang, Hannah Wentzel
Andrew Hill
University of Liverpool
Corresponding Author
Ahmed Abdulamir
College of Medicine, Alnahrain University, Baghdad, Iraq
Sabeena Ahmed
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh,
Asma Asghar
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Olufemi Emmanuel Babalola
Bingham University / Lagos University, Nigeria
Rabia Basri
Fatima Memorial Hospital, Lahore, Pakistan
Carlos Chaccour
Barcelona Institute for Global Health, Clinica Universidad de Navarra, Spain
Aijaz Zeeshan Khan Chachar
Fatima Memorial Hospital, Lahore, Pakistan
Abu Tauib Mohammed Chowdhury
Xi'an Jiaotong University Medical College First Affiliated Hospital, Shaannxi, China
Ahmed Elgazzar
Faculty of Medicine, Benha University, Benha, Egypt
Leah Ellis
Faculty of Medicine, Imperial College, London, UK
Jonathan Falconer
Department of Infectious Diseases, Chelsea and Westminster Hospital, London, UK
Anna Garratt
Department of Infectious Diseases, University Hospital of Wales, Cardiff and Vale University Health Board, UK
Basma Hany
Faculty of Medicine, Benha University, Benha, Egypt
Hashim A Hashim
Alkarkh Hospital, Alatefiya, Baghdad, Iraq
Wasim Ul Haque
Department of Nephrology, BIRDEM General Hospital, Dhaka, Bangladesh
Arshad Hayat
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Shuixiang He
Xi'an Jiaotong University Medical College First Affiliated Hospital, Shaanxi, China
Ramin Jamshidian
Jundishapur University School of Medical Sciences, Ahvaz, Iran
Wasif Ali Khan
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
Ravi Kirti
Department of General Medicine, All India Institute of Medical Sciences, Patna, India
Alejandro Krolewiecki
Instituto de Investigatiaciones de Enferedades Tropicales, Sede Regional Oran, Universidad National de Salta, Argentina
Carlos Lanusse
Laboratorio de Farmacologia, Universidad de Buenos Aires, Argentina
Jacob Levi
Department of Intensive Care, University College London, UK
Reaz Mahmud
Department of Neurology, Dhaka Medical College, Dhaka, Bangladesh
Sermand Ahmed Mangat
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Kaitlyn McCann
Faculty of Medicine, Imperial College, London, UK
Anant Mohan
Department of Pulmonary Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
Mortezza Shakshi Niaee
Qazvin Science and Technology Park, Qazvin, Iran
Nurullah Okumus
Department of Neonatology, Afyonkarahisar Health Sciences University, Afkonkarahisar, Turkey
Victoria Pilkington
Oxford University, Clinical Academic Graduate School, University of Oxford, UK
Chinmay Saha Podder
Debidwar Upazila Health Complex, Debidwar, Comilla, Bangladesh
Ambar Qavi
Faculty of Medicine, Imperial College, London, UK
Houssam Raad
Biotherapies e Maladies Genetiques et Cancer, Universite Bordeaux, Segalen, France
Mohammaed Sadegh Rezai
Pediatric Infectious Diseases Research Centre, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, India
The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
This study reports on a clinical trial.
The author has confirmed that this trial has been registered with an ICMJE-approved registry, and the trial registration ID has been provided in the text. If the article reports on a study that was registered retrospectively, a statement explaining why the study was not registered in advance has been provided in the text.
The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.
This is a preprint. It has not completed peer review.
Systematic Review
Andrew Hill, Ahmed Abdulamir, Sabeena Ahmed, Asma Asghar, Olufemi Emmanuel Babalola, Rabia Basri, Carlos Chaccour, Aijaz Zeeshan Khan Chachar, Abu Tauib Mohammed Chowdhury, Ahmed Elgazzar, Leah Ellis, Jonathan Falconer, Anna Garratt, Basma Hany, Hashim A Hashim, Wasim Ul Haque, Arshad Hayat, Shuixiang He, Ramin Jamshidian, Wasif Ali Khan, Ravi Kirti, Alejandro Krolewiecki, Carlos Lanusse, Jacob Levi, Reaz Mahmud, Sermand Ahmed Mangat, Kaitlyn McCann, Anant Mohan, Mortezza Shakshi Niaee, Nurullah Okumus, Victoria Pilkington, Chinmay Saha Podder, Ambar Qavi, Houssam Raad, Mohammaed Sadegh Rezai, Surapaneni Sasank, Veerapaneni Spoorthi, Tejas Suri, Junzheng Wang, Hannah Wentzel
Andrew Hill
University of Liverpool
Corresponding Author
Ahmed Abdulamir
College of Medicine, Alnahrain University, Baghdad, Iraq
Sabeena Ahmed
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh,
Asma Asghar
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Olufemi Emmanuel Babalola
Bingham University / Lagos University, Nigeria
Rabia Basri
Fatima Memorial Hospital, Lahore, Pakistan
Carlos Chaccour
Barcelona Institute for Global Health, Clinica Universidad de Navarra, Spain
Aijaz Zeeshan Khan Chachar
Fatima Memorial Hospital, Lahore, Pakistan
Abu Tauib Mohammed Chowdhury
Xi'an Jiaotong University Medical College First Affiliated Hospital, Shaannxi, China
Ahmed Elgazzar
Faculty of Medicine, Benha University, Benha, Egypt
Leah Ellis
Faculty of Medicine, Imperial College, London, UK
Jonathan Falconer
Department of Infectious Diseases, Chelsea and Westminster Hospital, London, UK
Anna Garratt
Department of Infectious Diseases, University Hospital of Wales, Cardiff and Vale University Health Board, UK
Basma Hany
Faculty of Medicine, Benha University, Benha, Egypt
Hashim A Hashim
Alkarkh Hospital, Alatefiya, Baghdad, Iraq
Wasim Ul Haque
Department of Nephrology, BIRDEM General Hospital, Dhaka, Bangladesh
Arshad Hayat
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Shuixiang He
Xi'an Jiaotong University Medical College First Affiliated Hospital, Shaanxi, China
Ramin Jamshidian
Jundishapur University School of Medical Sciences, Ahvaz, Iran
Wasif Ali Khan
International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
Ravi Kirti
Department of General Medicine, All India Institute of Medical Sciences, Patna, India
Alejandro Krolewiecki
Instituto de Investigatiaciones de Enferedades Tropicales, Sede Regional Oran, Universidad National de Salta, Argentina
Carlos Lanusse
Laboratorio de Farmacologia, Universidad de Buenos Aires, Argentina
Jacob Levi
Department of Intensive Care, University College London, UK
Reaz Mahmud
Department of Neurology, Dhaka Medical College, Dhaka, Bangladesh
Sermand Ahmed Mangat
Department of Medicine, Combined Military Hospital, Lahore, Pakistan
Kaitlyn McCann
Faculty of Medicine, Imperial College, London, UK
Anant Mohan
Department of Pulmonary Critical Care and Sleep Medicine, All India Institute of Medical Sciences, New Delhi, India
Mortezza Shakshi Niaee
Qazvin Science and Technology Park, Qazvin, Iran
Nurullah Okumus
Department of Neonatology, Afyonkarahisar Health Sciences University, Afkonkarahisar, Turkey
Victoria Pilkington
Oxford University, Clinical Academic Graduate School, University of Oxford, UK
Chinmay Saha Podder
Debidwar Upazila Health Complex, Debidwar, Comilla, Bangladesh
Ambar Qavi
Faculty of Medicine, Imperial College, London, UK
Houssam Raad
Biotherapies e Maladies Genetiques et Cancer, Universite Bordeaux, Segalen, France
Mohammaed Sadegh Rezai
Pediatric Infectious Diseases Research Centre, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, India
The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
This study reports on a clinical trial.
The author has confirmed that this trial has been registered with an ICMJE-approved registry, and the trial registration ID has been provided in the text. If the article reports on a study that was registered retrospectively, a statement explaining why the study was not registered in advance has been provided in the text.
The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.