Oral antivirals for COVID-19 can be game changers in low- and middle-income countries (LMICs). Challenges that may hinder current and future oral antiviral rollouts span use in special populations, drug-drug and herb-drug interactions, adverse events, development of resistance, black markets, and equity in access and prescribing. Future antivirals may address some of these barriers; however, health systems around the world should be equipped to receive and administer COVID-19 oral antivirals. Improvements in manufacturing capacity, community engagement, capacity for testing and linkage to care, and systems for surveillance and safety monitoring could "change the game" for LMICs, irrespective of any specific antiviral drug. Investments in health care infrastructure can promote resilience, not only for COVID-19 but also for future local and global health crises.
Keywords: COVID-19; antivirals; global health; health care infrastructure.