No Covid in Africa: why?

In an April 10 interview, American philanthropist Melinda Gates expressed her belief that the coronavirus pandemic will have the worst impact in the developing world. She said she foresees bodies lying around in the street of African countries. It is quite surprising to see that although there have been shocking reports of hospitals overwhelmed with patients in the US and in other Western countries, the billionaire philanthropist and others like her still choose to talk about dead bodies in Africa. Gates is not the only one to be predicting total doom in Africa. A report released by the United Nations Economic Commission for Africa (UNECA) in April stated: “….up to 3.3 million African people could lose their lives as a direct result of COVID-19.” And on April 6. Dr Matshidiso Moeti, WHO Regional Director for Africa stated that if we are not able to eradicate this virus in Africa the entire world will collapse. But the African apocalypse did not happen. Why ? The data are stubbornly telling us that Africa not only have lower death rates than the rest of the world, but also have less confirmed infections In DRCongo with a population of 90 000 000 and 600 Covid fatalities, this is a deathtoll of 0.0007% for the entire country. . Efforts have been made, particularly in Africa, to link the low morbi/mortality rates by Covid-19 to many possible influencers, among them, the median young age of the African population, population density variables, climate, etc. All of them do not achieve statistical relevance by any means. In our weblog « Malaria inhibits Covid » on www.malariaworld.org we discuss the possibility that the overwhelming impact of malaria in Subsaharan Africa might play a role. Both infections generate several immunoglobulins which are synergetic. In extension to the « hygiene hypothesis », the host immune system is conditioned by lifelong environmental encounters with micro- and macro-organisms, ranging from commensals to pathogens. Co-infections shape the host immune status, thereby influencing the development of inflammatory diseases, which can result in detrimental or beneficial effects. Helminth parasites have adapted to their hosts during long coevolution processes, which usually result in chronic disease with low mortality and variable morbidity. During this evolutionary coadaptation with their hosts, including vertebrate hosts, parasites have contributed to the modulation of several molecular and physiological host mechanisms, for example, the immune system. Siles-Lucas M, González-Miguel J, Geller R, Sanjuan R, Pérez-Arévalo J, Martínez-Moreno Á. Potential Influence of Helminth Molecules on COVID-19 Pathology. Trends Parasitol. 2021 Jan;37(1):11-14. More than 1 million people worldwide are infected by helminths, the highest load in sub Saharan Africa with 700 000 infections. One of the major helminthic diseases is schistosomiasis (bilharzia). The majority of individuals infected with schistosomiasis are asymptomatic, although non-specific signs of infection can include eosinophilia, microscopic haematuria. Eosinophils are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply. They form about 2 to 3% of WBC's. (Wikipedia). A review paper in 2009 stated that eosinophils are among among the most enigmatic of all cells of the immune system. Some experts even have expressed their concern that a Covid-19 vaccine which increases the eosinophil count could have harmful effects. Rosenberg HF, Dyer KD, Domachowske JB. Eosinophils and their interactions with respiratory virus pathogens. Immunol Res. 2009;43(1-3):128-137. doi:10.1007/s12026-008-8058-5 Simon H, -U, Karaulov A, V, Bachmann M, F: Strategies to Prevent SARS-CoV-2-Mediated Eosinophilic Disease in Association with COVID-19 Vaccination and Infection. Int Arch Allergy Immunol 2020;181:624-628. doi: 10.1159/0005093 Literature confirms the high eosinophil counts in the general population of helminth prevalent regions, much higher than in the modern urban "dewormed" world. Ilesanmi A, . O. Olalubi}, Prevalence of latent eosinophilia among occupational gardeners at Babcock University, Nigeria}, Asian Pacific Journal of Tropical Biomedicine},2016, 6, 511-515 An explanation of their action was already described in 1982. Schistosomiasis is characterized clinically by an increase in eosinophil counts in bone marrow and peripheral blood. This eosinophil response is also manifest pathologically by cell accumulation around the invading schistosomula and the parasite ova retained in host tissues. The ability of these cells to destroy multicellular parasites has been shown to be due to highly reactive oxygen reduction products or to release of cationic or major basic proteins from the granules. Adel A. F. Mahmoud, The Ecology of Eosinophils in Schistosomiasis, The Journal of Infectious Diseases, Volume 145, Issue 5, May 1982, Pages 613–622 Eosinophilia is a common finding in returning travellers and migrants, and in this group it often indicates an underlying helminth infection. Infections are frequently either asymptomatic or associated with non-specific symptoms Anna M. Checkley, Frances Sanderson. Eosinophilia in returning travellers and migrants from the tropics: Clinical Guidelines of the British Infection Society| Volume 60, ISSUE 1, P1-20, January 01, 2010 Stephan Ehrhardt and Gerd D. Burchard, Eosinophilia in Returning Travelers and Migrants. Dtsch Arztebl Int. 2008 Nov; 105(46): 801–807. In his study on the effect of Artemisia annua, Artemisia afra and Praziquantel on schistosomiasis infections J Munyangi found that the 3 treatments lowered the eosinophil count by 27 % from day 0 to day 28. Munyangi, J., Cornet-Vernet, L., Idumbo, M., Lu, C., Lutgen, P., Perronne, C., Ngombe, N., Bianga, J., Mupenda, B., Lalukala, P., Mergeai, G., Mumba, D., Towler, M., & Weathers, P. (2018). Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial. Phytomedicine : international journal of phytotherapy and phytopharmacology, 51, 233–240. Helminthic parasites are known to play a protective role. They induce regulatory T and B cells as well as anti-inflammatory cytokines (e.g. IL-10, TGF-β). Although the interaction between helminth infection and viral pneumonia is poorly defined, there is some evidence that helminth infection may moderate the process of pulmonary inflammation in viral infections. Hays R, Pierce D, Giacomin P, Loukas A, Bourke P, McDermott R (2020) Helminth coinfection and COVID-19: An alternate hypothesis. PLoS Negl Trop Dis 14(8): e0008628 Cotton S, Gonzales Santana B, Dalton JP. Schistosoma mansoni immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs). PLoS Negl Trop Dis. 2020 Jul 9;14(7):e0008470 A recent Spanish paper summarizes well the link between helminths and Covid-19. Parasites engineer strategies to maintain the host in an immune "silent" state. Helminths (worms) modify the immune system of their host to avoid immune ejection, a strategy that promotes their long-term survival and results in chronic infection, but that also has a bystander positive effect by protecting both the host and the parasite against the onset of inflammatory disorders. Helminth infection produces a whole array of effects, which is best described by the so called Th2-IL-10 axis. IL-10 is an anti-inflammatory cytokine abundantly produced by the Th2 CD4+ lymphocytes. During helminth infection, it inhibits the activity of Th1 cells, suppresses the bidirectional crosstalk between NK cells and myeloid dendritic cells, inhibits CD8+ cytotoxic T cell function and directs macrophage polarization to an immunosuppressive phenotype. It is now generally accepted, that what leads to the Acute Respiratory Failure in the Covid-19 disease is not the viral infection (i.e. the viral load) itself, but the extremely intense and seemingly uncontrolled inflammatory reaction as seen in the lungs of these patients. To sum, the Spanish authors believe that chronic helminth infection provides infected people with an unexpected wealth of protective mechanisms against the Covid-19 disease and its lethal complications. This protective mechanism is based on two legs : eosinophils and the Th2-IL-10 system. Rodriguez, Carlos. The global helminth belt and Covid-19: the new eosinophilic link, Journal Qeios, 2020/05/28 DO - 10.32388/IWKQH9.2 Coming back to studies in the « dewormed » Northern hemisphere, it was found that in the elderly IL-10(+) B cells generally decline. IL-10 is an essential cytokine, mainly produced by macrophages, and is responsible for suppressing proinflammatory response in various tissues. In elderly women, an increased Th1/Th2 ratio was found, due to a higher response of Th1 cells and lower response of Th2 cells. Kroesen BJ, Brouwer E, Boots AM. Aging-dependent decline of IL-10 producing B cells. 2016 Mar; 75:24-9. Dagdeviren S, Jung DY, Friedline RH, et al. IL-10 prevents aging-associated inflammation and insulin resistance in skeletal muscle. FASEB J. 2017;31(2):701-710. doi:10.1096/fj.201600832R Eosinopenia is often used as predictor of infection. In a Spanish study on 99 patients admitted for acute respiratory failure related to SARS-CoV-2 pneumonia 88% had eosinopenia at ICU admission and 33% developed eosinophilia during ICU stay. A French team noticed that the early phase of SARS-CoV-2 infection seems to be accompanied by eosinopenia. Conversely, several of the critically ill COVID-19 patients developed unexpected and unexplained eosinophilia. Silva JM, Costa AM, Tuna C, Ascensão M. Eosinopenia as predictor of infection in patients admitted to an internal medicine ward: a cross-sectional study. Porto Biomed J. 2020 Nov 11;5(6):e084.. Mateos Gonzalez M, Sierra Gonzalo E, Casado Lopez I, Arnalich Fernandez F, Beato Perez JL, Monge Monge D, et al. The prognostic value of eosinophil recovery in COVID-19: a multicentre, retrospective cohort study on patients hospitalised in Spanish hospitals. medRxiv. 2020;2020.08.18.20172874. Fraissé, M., Logre, E., Mentec, H. et al. Eosinophilia in critically ill COVID-19 patients: a French monocenter retrospective study. Crit Care 24, 635 (2020)