Coronavirus disease 2019 (COVID-19) has spread rapidly and extensively to most countries in the world, resulting in considerable mortality in Europe and the United States, as well as in numerous upper-middle-income countries in South America and Asia. Experts predicted millions of COVID-19 deaths in Africa because many countries in the continent rank poorly on the United Nations Development Programme's Human Development Index. However, more than 4 months after the first cases in Africa were detected, prevalence and mortality are still low. It remains unclear if Africa is really spared from substantial cases and deaths. However, differences between Africa and the most affected countries in reliable reporting and death registration, lockdown stringency, demography, sociocultural aspects, environmental exposures, genetics, and the immune system could help to explain the experience of COVID-19 in Africa.