Review
Immunology
Bhaswati Chatterjee, Suman S. Thakur
Summary: The SARS-CoV-2 virus uses an enzyme called RNA-dependent RNA polymerase (RdRp) for replication, which can be inhibited by Remdesivir. The combination treatment of Remdesivir with Baricitinib has shown better results in treating COVID-19, reducing recovery time and mortality rate. Simultaneously targeting virus replication enzymes and host human kinases may be the future strategy for SARS-CoV-2 therapeutics.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Sola Akinbolade, Diarmuid Coughlan, Ross Fairbairn, Glenn McConkey, Helen Powell, Dapo Ogunbayo, Dawn Craig
Summary: The COVID-19 pandemic has sparked an unprecedented surge in global drug discovery and clinical development for the coronavirus disease, with a majority of current trials focusing on monotherapies. Combination therapies are considered crucial for enhancing efficacy and tackling resistance, despite facing complex challenges in clinical and regulatory development.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Qunfeng Luo, Yunxi Zheng, Jin Zhang
Summary: This review summarizes the progress of combination therapies targeting SARS-CoV-2, which involve at least one small molecule in order to block the viral life cycle and alleviate host complications. It provides significant inspiration for further development of treatment strategies against SARS-CoV-2, particularly its mutant variants.
FRONTIERS IN BIOSCIENCE-LANDMARK
(2022)
Review
Clinical Neurology
Milo Gatti, Fabrizio De Ponti, Federico Pea
Summary: Relevant drug interactions between psychotropic agents and COVID-19 therapies may lead to clinically significant issues, mainly due to pharmacodynamic and pharmacogenetic factors, requiring tailored management strategies based on disease severity and clinical conditions.
Review
Pharmacology & Pharmacy
Barbara Costa, Nuno Vale
Summary: The COVID-19 pandemic has posed an unprecedented challenge in finding effective drugs, with anticancer drugs showing potential for repurposing. Clinical management needs further improvement to effectively treat this infection.
Review
Infectious Diseases
Daniele Focosi, Fabrizio Maggi, Alessandra D'Abramo, Emanuele Nicastri, David J. Sullivan
Summary: After the third year of the COVID-19 pandemic, immunocompromised patients face persistent infection and ineffective treatment with standard antiviral monotherapy. Combined antiviral therapies can mitigate these consequences.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Christopher A. MacRaild, Muzaffar-Ur-Rehman Mohammed, Faheem, Sankaranarayanan Murugesan, Ian K. Styles, Amanda L. Peterson, Carl M. J. Kirkpatrick, Matthew A. Cooper, Enzo A. Palombo, Moana M. Simpson, Hardik A. Jain, Vinti Agarwal, Alexander J. McAuley, Anupama Kumar, Darren J. Creek, Natalie L. Trevaskis, Seshadri S. Vasan
Summary: SARS-CoV-2 is the cause of the COVID-19 pandemic, and the development of new drugs and vaccines is critical in managing it. Repurposing approved drugs has been an effective method for developing new treatments quickly. By applying filters and evaluating the activity of thousands of compounds, researchers have identified 12 FDA-approved drugs with potential mechanisms for treating COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Letter
Medicine, General & Internal
Kesara Na-Bangchang, Supatra Porasuphatana, Juntra Karbwang
Summary: This article emphasizes the necessity of proper research design in prescribing drug treatment, both scientifically and ethically. Research articles and guidelines related to COVID-19 therapy were searched from the PubMed database. The results show that only remdesivir and tocilizumab have been approved by the US FDA for clinical use in moderate and severe COVID-19 cases. Further research is needed to confirm the efficacy and safety of favipiravir, ivermectin, and andrographolide against COVID-19 at different stages.
ARCHIVES OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Summary: The authors of the study reported the interim results of using four repurposed antiviral drugs (remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a) in hospitalized COVID-19 patients. The study showed that these drug regimens had little or no effect on overall mortality, initiation of ventilation, and duration of hospital stay.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Editorial Material
Microbiology
Miguel Angel Martinez
Summary: While some drugs have shown limited impact on COVID-19, recent research has indicated that plitidepsin has potent antiviral activity, making it a promising alternative therapeutic option for COVID-19.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, General & Internal
Lisa LaVange, Stacey J. Adam, Judith S. Currier, Elizabeth S. Higgs, Lora A. Reineck, Eric A. Hughes, Sarah W. Read
Summary: The ACTIV public-private partnership developed and launched 9 master protocols within a short time frame to evaluate multiple investigational therapeutic agents for COVID-19, serving different patient populations. These protocols were designed to test various drug classes, efficiently selecting effective treatments while eliminating ineffective or unsafe methods.
ANNALS OF INTERNAL MEDICINE
(2021)
Review
Infectious Diseases
Kamini Govender, Anil Chuturgoon
Summary: The COVID-19 pandemic caused by SARS-CoV-2 has had a profound impact on global healthcare systems and economies. There is a need to find effective therapeutic strategies to combat the unprecedented number of cases reported worldwide. Drug repurposing provides a viable option for the discovery of efficacious drugs for COVID-19.
Review
Immunology
Surojit Banerjee, Debadri Banerjee, Anupama Singh, Sumit Kumar, Deep Pooja, Veerma Ram, Hitesh Kulhari, Vikas Anand Saharan
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, quickly spreading worldwide and causing a global pandemic and healthcare emergency. Initial treatment options for COVID-19 were limited due to the absence of approved drugs or vaccines. Some repurposed drugs received emergency use authorization, but faced challenges such as severe adverse effects or lack of clinical data. New molecules have shown varying therapeutic efficacy against different variants of SARS-CoV-2, requiring further investigation.
Review
Pharmacology & Pharmacy
Miguel Angel Martinez
Summary: This article discusses whether drug repurposing is the best strategy for developing effective therapies to treat COVID-19 and other viral human infections.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Illya Aronskyy, Yosef Masoudi-Sobhanzadeh, Antonio Cappuccio, Elena Zaslavsky
Summary: The COVID-19 pandemic has led to millions of deaths and social distress worldwide, creating an urgent need for therapeutic solutions. Computational drug repurposing offers a promising alternative by enabling fast prioritization of existing compounds and producing actionable predictions for clinical trials targeting viral proteins and host pathways.
DRUG DISCOVERY TODAY
(2021)
Article
Immunology
Lauren Jennings, Tracy Kellermann, Matthew Spinelli, Zukiswa Nkantsu, Dolphina Cogill, Marije van Schalkwyk, Eric Decloedt, Gert van Zyl, Catherine Orrell, Monica Gandhi
Summary: The study showed that in HIV treatment, the low-cost lateral flow urine tenofovir rapid assay can help predict the risk of treatment failure and detect resistance to different drugs, avoiding unnecessary high costs.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2022)
Article
Public, Environmental & Occupational Health
Jamie Forrest, Angeli Rawat, Felipe Duailibe, Christina M. Guo, Sheila Sprague, Paula McKay, Gilmar Reis, Edward J. Mills
Summary: In response to the COVID-19 pandemic, clinical research groups developed trial protocols, but only a small portion were implemented and generated new evidence. Successful clinical trials can be attributed to resilient trial infrastructures, and the health system resiliency framework provides a useful framework for evaluating COVID-19 therapies.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Article
Public, Environmental & Occupational Health
Gilmar Reis, Eduardo Augusto dos Santos Moreira-Silva, Daniela Carla Medeiros Silva, Lehana Thabane, Aline Cruz Milagres, Thiago Santiago Ferreira, Castilho Vitor Quirino dos Santos, Vitoria Helena de Souza Campos, Ana Maria Ribeiro Nogueira, Ana Paula Figueiredo Guimaraes de Almeida, Eduardo Diniz Callegari, Adhemar Dias de Figueiredo Neto, Leonardo Cancado Monteiro Savassi, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Rosemary Oliveira, Ofir Harari, Jamie Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Alla Glushchenko, Craig R. Rayner, Eric J. Lenze, Angela M. Reiersen, Gordon H. Guyatt, Edward J. Mills
Summary: Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital. The trial showed a higher probability of superiority (99.8%) surpassing the prespecified threshold of 97.6%.
LANCET GLOBAL HEALTH
(2022)
Editorial Material
Medicine, General & Internal
Edward J. Mills, Gilmar Reis
Article
Public, Environmental & Occupational Health
Fergal P. Mills, Gilmar Reis, Lindsay A. Wilson, Kristian Thorlund, Jamie I. Forrest, Christina M. Guo, David R. Boulware, Edward J. Mills, TOGETHER Investigators
Summary: According to two published randomized trials, early treatment with fluvoxamine has shown clinical benefits for symptomatic adults with COVID-19 compared to placebo. A cost-consequence analysis was conducted using the largest trial, TOGETHER trial, to assess the health system benefits of preventing progression to severe COVID-19 in outpatient populations in the United States. The analysis showed that fluvoxamine administration to high-risk symptomatic outpatients was cost-saving and resulted in fewer hospitalization days compared to standard of care. Nirmatrelvir-ritonavir also demonstrated cost savings despite its higher acquisition cost.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)
Article
Medicine, Research & Experimental
Oriol Mitja, Gilmar Reis, David R. Boulware, Adam M. Spivak, Ammar Sarwar, Christine Johnston, Brandon Webb, Michael D. Hill, Davey Smith, Peter Kremsner, Marla Curran, David Carter, Jim Alexander, Marc Corbacho, Todd C. Lee, Katherine Huppler Hullsiek, Emily G. McDonald, Rachel Hess, Michael Hughes, Jared M. Baeten, Ilan Schwartz, Luanne Metz, Lawrence Richer, Kara W. Chew, Eric Daar, David Wohl, Michael Dunne
Summary: This study conducted a pooled analysis of individual participant data from 11 randomized controlled trials to evaluate the efficacy of hydroxychloroquine (HCQ) in outpatients with mild COVID-19. The results suggest that HCQ does not show significant effects on viral clearance and hospitalization rate, and therefore, the use of HCQ in mild COVID-19 outpatients should be discontinued to reduce the risk of disease progression.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Letter
Biotechnology & Applied Microbiology
Michael Dodds, James Roberts, Brian Finrow
NATURE BIOTECHNOLOGY
(2022)
Review
Infectious Diseases
Kevin Meesters, Tinsae Alemayehu, Sofia Benou, Danilo Buonsenso, Eric H. Decloedt, Veshni Pillay-Fuentes Lorente, Kevin J. Downes, Karel Allegaert
Summary: Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance in low and middle income countries (LMIC). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. This article outlines the effects of growth, maturation, and comorbidities on pharmacokinetics in LMIC children.
Article
Medicine, General & Internal
Gilmar Reis, Eduardo Augusto dos Santos Moreira Silva, Daniela Carla Medeiros Silva, Lehana Thabane, Vitoria Helena de Souza Campos, Thiago Santiago Ferreira, Castilho Vitor Quirino dos Santos, Ana Maria Ribeiro Nogueira, Ana Paula Figueiredo Guimaraes Almeida, Leonardo Cancado Monteiro Savassi, Adhemar Dias de Figueiredo Neto, Carina Bitaraes, Aline Cruz Milagres, Eduardo Diniz Callegari, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Rosemary Oliveira, Ofir A. Harari, Lindsay A. Wilson, Jamie Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Christina M. Guo, Gordon H. Guyatt, Craig R. Rayner, David R. Boulware, Nicole Ezer, Todd C. Lee, Emily Gibson McDonald, Mona Bafadhel, Christopher Butler, Josue Rodrigues Silva, Mark J. Dybul, Edward Mills
Summary: This study aimed to determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. The results showed that the proportion of patients observed in an emergency setting or hospitalized due to COVID-19 was lower in the treatment group than the placebo group, suggesting that the combination treatment can reduce the risk of disease progression.
ANNALS OF INTERNAL MEDICINE
(2023)
Article
Health Care Sciences & Services
Russanthy Ruthiran Velummailum, Chelsea McKibbon, Darren R. Brenner, Elizabeth Ann Stringer, Leeland Ekstrom, Louis Dron
Summary: The preferred evidence from large randomized controlled trials is difficult to use in certain scenarios, so decision makers are increasingly considering real-world data as an alternative. However, identifying suitable real-world data to serve as an external control arm for a single-arm trial presents challenges in terms of identification, outcome, and time selection. This viewpoint article provides an overview of these technical challenges and offers practical solutions for researchers to analyze external data for comparative efficacy through detailed planning, data collection, and record linkage.
JOURNAL OF MEDICAL INTERNET RESEARCH
(2023)
Article
Medicine, General & Internal
Gilmar Reis, Eduardo A. S. Moreira Silva, Daniela C. Medeiros Silva, Lehana Thabane, Vitoria H. S. Campos, Thiago S. Ferreira, Castilho V. Q. Santos, Ana M. R. Nogueira, Ana P. F. G. Almeida, Leonardo C. M. Savassi, Adhemar D. Figueiredo-Neto, Ana C. F. Dias, Adelino M. Freire Junior, Carina Bitares, Aline C. Milagres, Eduardo D. Callegari, Maria I. C. Simplicio, Luciene B. Ribeiro, Rosemary Oliveira, Ofir Harari, Lindsay A. Wilson, Jamie I. Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Christina M. Guo, Eve H. Limbrick-Oldfield, Steve Kanters, Gordon H. Guyatt, Craig R. Rayner, Christopher Kandel, Mia J. Biondi, Robert Kozak, Bettina Hansen, M. Atif Zahoor, Paul Arora, Colin Hislop, Ingrid Choong, Jordan J. Feld, Edward J. Mills, Jeffrey S. Glenn
Summary: A trial on predominantly vaccinated outpatients with Covid-19 in Brazil and Canada found that the incidence of hospitalization or emergency department visits within 28 days was significantly lower among patients who received a single dose of pegylated interferon lambda compared to those who received a placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Correction
Public, Environmental & Occupational Health
G. Reis, dos Santos E. A. Moreira-Silva, Medeiros D. C. Silva
LANCET GLOBAL HEALTH
(2022)
Article
Health Care Sciences & Services
Gilmar Reis, Eduardo Augusto dos Santos Moreira Silva, Daniela Carla Medeiros Silva, Lehana Thabane, Aline Cruz Milagres, Thiago Santiago Ferreira, Castilho Vitor Quirino dos Santos, Adhemar Dias de Figueiredo Neto, Eduardo Diniz Callegari, Leonardo Cancado Monteiro Savassi, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Rosemary Oliveira, Ofir Harari, Holly Bailey, Jamie Forrest, Alla Glushchenko, Sheila Sprague, Paula McKay, Craig R. Rayner, Hinda Ruton, Gordon H. Guyatt, Edward J. Mills
Summary: In this study, it was found that metformin did not provide any clinical benefit compared to placebo for ambulatory high-risk patients with early COVID-19 in terms of reducing the need for hospitalization or retention in an emergency setting due to worsening COVID-19. There were no significant differences observed between metformin and placebo for other secondary clinical outcomes.
LANCET REGIONAL HEALTH-AMERICAS
(2022)
Letter
Public, Environmental & Occupational Health
Gilmar Reis, Edward Mills
LANCET GLOBAL HEALTH
(2022)
Letter
Public, Environmental & Occupational Health
Michael G. Dodds, Eileen B. Doyle, Angela M. Reiersen, Fran Brown, Craig R. Rayner
LANCET GLOBAL HEALTH
(2022)