The incidence and mortality of COVID-19, according to the World Health Organization reports, shows a noticeable difference between North America, Western Europe, and South Asia on one hand and most African countries on the other hand, especially the malaria-endemic countries. Although this observation could be attributed to limited testing capacity, mitigation tools adopted and cultural habits, many theories have been postulated to explain this difference in prevalence and mortality. Because death tends to occur more in elders, both the role of demography, and how the age structure of a population may contribute to the difference in mortality rate between countries were discussed. The variable distribution of the ACEI/D and the ACE2 (C1173T substitution) polymorphisms has been postulated to explain this variable prevalence. Up-to-date data regarding the role of hydroxychloroquine (HCQ) and chloroquine (CQ) in COVID-19 have been summarized. The article also sheds lights on how the similarity of malaria and COVID-19 symptoms can lead to misdiagnosis of one disease for the other or overlooking the possibility of co-infection. As the COVID-19 pandemic threatens the delivery of malaria services, such as the distribution of insecticide-treated nets (ITNs), indoor residual spraying, as well as malaria chemoprevention there is an urgent need for rapid and effective responses to avoid malaria outbreaks.