February 2021. Improving our response to the ongoing COVID-19 pandemic in Africa requires regularly updated information, constant innovation, and considerable support towards research and development (R&D) for priorities that respond to the African realities. Shaping the research agenda and stimulating the generation, translation, and dissemination of valuable knowledge is one of the core functions of the African Academy of Sciences (AAS), African Centre for Disease Control (Africa CDC), and WHO-AFRO. We need answers to a list of critical research questions that respond to the current realities on the African continent to guide the COVID-19 outbreak control efforts