The COVID-19 pandemic has been a major threat to people and healthcare systems around the world. Each region of the world has had unique factors such as culture, demographics, socioeconomic and the political landscape that has either fueled or mitigated the severity of the pandemic. For example, the 2021 Indian Kumbh Mela festival fueled a devastating wave of the pandemic in India. Similarly, the pandemic in the United States has in part been fueled an epidemic of disinformation that led to a growing number of anti-vaxxers, and those who are opposed to COVID-19 prevention guidelines set by agencies like the Centers for Disease Control and Prevention. In Africa, burial practices in Liberia and the Democratic Republic of Congo once fueled the Ebola epidemic. Likewise, in the context of COVID-19, there are factors that are unique to Africa that may have either fueled or mitigated the severity of the pandemic. The anti-COVID-19 measures in many African countries significantly affected household income without commensurate deployment of palliative measures to cushion the effect. Fortunately, the pandemic has run a relatively milder course in sub-Saharan Africa—defying earlier devastating projections. Therefore, to be prepared for the next pandemic, African governments must involve critical stakeholders such as religious and traditional leaders, strengthen current disease surveillance systems and invest in systems that encourage private investments in local vaccine manufacturing.