An original article setting forth crossover prophylaxis as a hypothesis for the superior COVID outcomes in sub-Saharan Africa is Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions - A Clue to Treatment? It can be read on the Elsevier SSRN preprint server referenced as https://dx.doi.org/10.2139/ssrn.3586954 or downloaded locally as a PDF here.
These studies arose out of a planned educational trip to Africa scheduled for March, 2020. It was noted that the first COVID patients arrived in New York City and Lagos Nigeria at about the same time. The results were quite different. Through March and April, it was noted that the infection and death rate in the industrialized West, particularly New York State and New York City climbed rapidly while the infection and death rates of other countries lagged behind. It was noted that India in particular, unexpectedly lagged behind the West in terms of coronavirus deaths.
These early observations suggested an inverse relationship between a country's malaria prevalence and its coronavirus death rate. A closer look was warranted. To test the hypothesis that a country's prevalence of malaria was somehow inversely related to its prevalence of or susceptibility to coronavirus, the six malaria-endemic countries were studied. The six sub-Saharan African countries (Nigeria, Congo, Mozambique, Uganda, Niger and Cote d'Ivoire) were selected for this study because all six are thought to have a higher prevalence of malaria overall than other countries. The WHO's World Malaria Report for 2019 states that "nineteen countries in sub-Saharan Africa and India carried almost 85% of the global malaria burden." These "six countries accounted for more than half of all malaria cases worldwide." They are Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda (5%), and Cote d'Ivoire, Mozambique and Niger (4% each).*
As one might expect, the data has changed slightly over the months. The original conclusions remain unchanged. The original paper, published in early May, asserted a "hundred-fold" or "two orders of magnitude" disparity in the fatality rates of West and SSA. The term "hundred-fold," used to describe the differences in the population-adjusted data, was used eight times in the original article. The population-adjusted fatality rate in SSA was asserted to be <1% of that of the West. Now, seven months into the pandemic, that original conclusion remains intact. The population-adjusted fatality rate in the U.S. and Western countries remains 200 times that of SSA, still a "hundred-fold" or "two orders of magnitude." The overall population-adjusted fatality rate in SSA is still <1% of the West.
Age Adjustment
In October, 2020, in anticipation of presentation of the SSA mortality data at a conference in Washington, and in order to make it as accurate as possible, the data was adjusted for age. There is no doubt that age disparities exist between the various countries. The age disparities do not invalidate the data or the basic conclusions of the research. The overall mortality ratios remain intact. These age-adjusted results are discussed further in the Data section.
The Crossover Hypothesis
All of this begs the question, what distinguishes these six malaria-endemic countries in terms of their residents' propensity toward coronavirus infection. We know three facts: 1) that malaria is so prevalent in these countries that arriving travelers are almost certain to be taking anti-malarial prophylactic drugs; 2) historically, hydroxychloroquine is the most common antimalarial drug and most of the modern drugs are hydroxychloroquine quinoline analogs; and 3) most of a nations COVID-19 infections are caused, at least initially, by seeding by arriving travelers. Based upon these facts it was hypothesized that rates of COVID-19 infections in these countries are so much lower because there exists a crossover prophylactic effect between hydroxychloroquine or newer antimalarial drugs and coronavirus. This crossover prophylactic effect is hypothesized to kill or at least mitigate coronavirus infections in arriving travelers such that they do not transmit the infection to the inhabitants of these six nations.
The first paper, proposing the crossover hypothesis was written on April 27, 2020. Markedly Lower Rates of Coronavirus Infection and Fatality in Malaria-Endemic Regions - A Clue to Treatment? (April 27, 2020). https://dx.doi.org/10.2139/ssrn.3586954.
As the high rate of coronavirus infection was noted in New York City in the first few months of the COVID pandemic, that high mortality rate in New York City was generally attributed to racial disparity, poverty and other generally recognized social determinants of disease. The evolving African experience with COVID indicated that there was some other factor in play. At second paper was written comparing coronavirus fatality in New Your City to another large crowed city, Lagos, Nigeria. A Tale of Two Cities - Lagos, Nigeria's Apparent Success in the War Against COVID-19 (Crossover Prophylaxis Against Coronavirus by Antimalarial Agents) (June 16, 2020). https://dx.doi.org/10.2139/ssrn.3628644 or downloaded locally as a PDF here.
The comparative fatality data, initially reported in the first paper on about May 1, 2020, has now been followed from May 1, 2020 to the present. The comparative fatality data remains about 200 times worse in the West and the U.S. on a raw, population-adjusted basis. It is 35 times worse on an age-adjusted basis. The comparative fatality data, initially reported on about May 1, 2020, has now been followed from May 1, 2020 to the present. That comparative fatality data comparing SSA with the industrialized West including the U.S., the more favorable COVID outcomes in SSA, are the subjects of this website.
* World malaria report 2019. World Health Organization 2019; published Dec 4: https://www.who.int/news-room/feature-stories/detail/world-malaria-report-2019. (accessed Apr 26, 2020).