Background: The COVID-19 respiratory illness caused by the SARS-CoV-2 has been a major cause of morbidity and mortality worldwide since the first reported case in Wuhan, China. A year has passed since pandemic began, and the reasons for different COVID-19 burden variation across continents keep puzzling the general public. Main body of the abstract: Since the COVID-19 pandemic started, published research articles have addressed the epidemiological risk factors, host factors, susceptibility and immunity. To ascertain possible reasons for the different rates of COVID-19 infections between Africa and other continents, we summarized the up-to-date scientific literature to identify possible arguments in this regard. Available literature suggests that demographic, epidemiological, sociological, genetic and immunological factors contribute in the COVID-19 severity and the susceptibly to SARS-CoV-2. Short conclusion: This review summarizes existing data and discusses reasons for differential COVID-19 burden across continents. The arguments mentioned herein will be helpful to guide future experimental studies to test different hypotheses.