COVID-19 Therapeutics for Low- and Middle-Income Countries: A Review of Candidate Agents with Potential for Near-Term Use and Impact
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Abstract
Low- and middle-income countries (LMICs) face significant challenges in the control of COVID-19, given limited resources, especially for inpatient care. In a parallel effort to that for vaccines, the identification of therapeutics that have near-term potential to be available and easily administered is critical. Using the United States (US), European Union (EU), and World Health Organization (WHO) clinical trial registries, we reviewed COVID-19 therapeutic agents currently under investigation. The search was limited to oral or potentially oral agents, with at least a putative anti-SARS-CoV-2 virus mechanism and with at least five registered trials. The search yielded 1,001, 203, and 1,128 trials, in the US, EU, and WHO trial registers, respectively. These trials covered 13 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics with established safety profiles. The available evidence regarding proposed mechanisms of action, potential limitations, and trial status is summarized. The results of the search demonstrate few published studies of high quality, a low proportion of trials completed, and the vast majority with negative results. These findings reflect limited investment in COVID-19 therapeutics development compared with vaccines. We also identified the need for better coordination of trials of accessible agents and their combinations in LMICs. To prevent COVID-19 from becoming a neglected tropical disease, there is a critical need for rapid and coordinated efforts in the evaluation and deployment of those agents found to be efficacious.
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SciScore for 10.1101/2021.03.22.21253621: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This limitation of available and accurate testing in LMICs could pose a threefold challenge: impeding modeling of the spread of the pandemic to facilitate well-planned trials, reducing identification and recruitment of proven …
SciScore for 10.1101/2021.03.22.21253621: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This limitation of available and accurate testing in LMICs could pose a threefold challenge: impeding modeling of the spread of the pandemic to facilitate well-planned trials, reducing identification and recruitment of proven cases, and further limiting diagnostic capacity for direct research use. Lastly, these interventions require trial expertise in multiple clinical settings: as treatment of severe, hospitalizing disease to reduce morbidity and mortality, as treatment of mild or moderate disease to reduce progression and transmission of disease, and as prophylactic or presumptive treatment. Indeed, targeted prophylaxis or presumptive treatment to high risk groups may be one of the more promising roles for such agents, with examples of success in LMICs with meningococcal disease113 and malaria114. Though these challenges are significant, they are not insurmountable. New drug candidates appear rapidly and a coordinated adaptive trial design should be used. As the clinical context of this disease is global, focused clinical endpoints that do not require extensive resources can provide rigor without burdening researchers with added cost and complexity. Designing such trials requires broad expertise and thus broad collaboration. Such trial protocols can be then distributed, decreasing burdens on aspiring trialists and increasing sample sizes and sites, and thus improving power and generalizability of findings. Indeed, some or all of the above approaches have been used by groups...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04414618 Completed A Study of Opaganib in Coronavirus Disease 2019 Pneumonia NCT04467840 Recruiting Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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