COVID-19 therapeutics for low- and middle-income countries: a review of re-purposed candidate agents with potential for near-term use and impact

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, European Union, and World Health Organization 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 3 registered trials. We describe the available evidence regarding agents that met these criteria and additionally discuss the need for additional investment by the global scientific community in large well-coordinated trials of accessible agents and their combinations in LMICs. The search yielded 636, 175, and 930 trials, in the US, EU, and WHO trial registers, respectively. These trials covered 17 oral or potentially oral repurposed agents that are currently used as antimicrobials and immunomodulatory therapeutics and therefore have established safety. The available evidence regarding proposed mechanism of actions, clinical efficacy, and potential limitations is summarized. We also identified the need for large well-coordinated trials of accessible agents and their combinations in LMICs. Several repurposed agents have potential to be safe, available, and easily administrable to treat COVID-19. To prevent COVID-19 from becoming a neglected tropical disease, there is critical need for rapid and coordinated effort in their evaluation and the deployment of those found to be efficacious.