COVID-19 Therapeutics for Low- and Middle-Income Countries: A Review of Candidate Agents with Potential for Near-Term Use and Impact.

Daniel Maxwell,Alejandro Llanos-Cuentas,Roly Gosling,Oliver Sabot,James B Cutrell,Ally Olotu,Michelle S Hsiang,Ahmad Hachem,Kelly C Sanders

doi:10.4269/ajtmh.21-0200

Abstract

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.

Highlights

The coronavirus disease 2019 (COVID-19) pandemic is causing devastating long-term health and socioeconomic impact in low- and middle-income countries (LMICs).[1]
Because the World Health Organization (WHO) ICTRP is a combination of the United States (US), European Union (EU), and other registers such as the Chinese Clinical Trial Registry, we present a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the WHO ICTRP search (Figure 1)
Examples of current uses, mechanism of action, potential limitations, and number and status of trials are shown in Table 1 and summarized

Summary

Introduction

The coronavirus disease 2019 (COVID-19) pandemic is causing devastating long-term health and socioeconomic impact in low- and middle-income countries (LMICs).[1] lower population density and younger age demographics in some LMICs may be protective against high COVID-19 mortality,[2] poor health infrastructure, including limited numbers of hospital beds, health care providers, and basic supplies, can lead to overwhelmed local health systems with relatively few cases.[3] vaccine research and deployment have moved forward at an unprecedented pace,[4,5] therapeutic development has not received the same level of political and financial commitment. As has been the case with other vaccine-preventable illnesses such as bacterial meningitis, pertussis, and influenza, therapeutics can play an important role in disease control alongside vaccines

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