By William Parker1, Jon D. Laman2, Dawit Wolday3 and Tobias F. Rinke de Wit4,5

Correspondence should be addressed to William.Parker@WilliamParkerLab.org

Predictions regarding clinical manifestation of COVID-19 in low-income countries can be based on evolutionary theory.

In 2010, Parker noted in The Evolution and Medicine Review that “biome depletion,” the loss of helminths from the ecosystem of the human body, is a critical evolutionary mismatch which leads to autoimmune disease, with viral infections serving as “triggers” [1]. A decade later, as clinical data from patients with COVID became public, investigators noticed that severe cases of COVID were associated with autoimmune or autoimmune-like reactions [2]. Based on these observations, Parker predicted in a May 2020 Face Book post that individuals in developing countries who were exposed to helminths would have less severe reactions to COVID due to immune modulation induced by the symbionts. Independently, Wolday and Rinke de Wit submitted a letter in May 2020 to The Lancet making similar predictions, based on their previous extensive research on HIV and the immune system of Ethiopians, but The Lancet declined to publish.

Robins and Gildner submitted an article in July 2020 to Evolution, Medicine and Public Health discussing the potential role of soil-transmitted helminths in attenuating severe reactions to the SARS-CoV-2 virus [3]; the article was published in October 2020. In August, Hays and colleagues published a similar view, asserting that helminths were likely to downmodulate severe adverse reactions to the SARS-CoV-2 virus [4].  Early the next year, Parker, Sarafian, Broverman, and Laman published another article in EMPH, describing in some detail the view that “system hygiene,” which includes sanitation and food preparation/storage technology, causes loss of helminths and protists, resulting in pathologic immune reactivity to viral infections, including SARS-CoV-2. Thus, multiple groups on different platforms used evolutionary medicine principles to predict that the presence of gut helminths and protists would be associated with reduced SARS-Co-V-2 severity.

Predictions are confirmed.

Inadequate medical facilities and an infrastructure unable to accommodate extensive social distancing led many experts to predict public health disasters in parts of Africa [5] and other low-income areas [6, 7]. Nevertheless, as data emerged during the second half of 2020, several studies reported the relatively light impact of COVID-19 in some developing countries [8-14]. An epidemiologic study first made available in October of 2020 on medRxiv indicated that, in addition to demographic factors such as a younger population, the presence of improved hygiene and the higher incidence of autoimmune disease were associated with increased mortality due to COVID [15]. However, a number of other factors, including underdiagnosis of COVID-19 due to paucity of diagnostics, underreporting of COVID-19 deaths, cross-protection through previous non-pathogenic coronavirus infections, BCG vaccination for tuberculosis, and genetic factors were proposed as factors that might account for the unanticipated observations, and questions remained [14, 16].

In May of 2021, Wolday, Rinke de Wit and 19 Ethiopian colleagues submitted for publication a study on 751 Ethiopian patients infected with SARS-CoV-2, 284 of whom had complex eukaryotic symbionts (helminths and/or protists) living in their intestines. Their study showed that the presence of complex eukaryotic symbionts, when corrected for gender, age, residence, education level, body mass index, and comorbidities, was associated with an odds ratio of 0.35 (0.26-0.48) for severe COVID. In their study, 2.4% of patients without complex eukaryotic symbionts died from COVID, whereas no patients with complex eukaryotic symbionts died. Evidence continues to emerge confirming the original predictions. For example, current data indicate that the blood borne protist responsible for malaria can alter immune function in a way that may be protective against SARS-CoV-2 infection [17, 18].

Conclusions

Evolutionary theory correctly predicted factors that profoundly influence COVID-19 severity in Africa, while dire predictions for the COVID-19 pandemic in Africa [5-7] were fortunately not fulfilled. First-hand observations by co-authors Wolday and de Wit, report emergency hospitals set up in Africa to deal with an anticipated crisis have not been needed, at least not prior to the recent spread of the Omicron variant.

The higher severity of the COVID-19 pandemic in high-income countries highlights the value of applying evolutionary principles to the field of medicine. Loss of helminths and protists in high-income countries was identified more than 50 years ago as a critical evolutionary mismatch [19-22], whose investigation in the intervening years could have considered strategies, including re-introduction of benign species, that could modulate immune function safely [1, 23, 24]. Based on currently available evidence, in particular the study by Wolday, Rinke de Wit and colleagues, such “biome reconstitution” could conceivably have mitigated a significant amount of the tragic clinical outcome of the COVID pandemic in high-income countries.

The primary reference for this commentary is: Wolday, D., Gebrecherkos, T., Arefaine, Z. G., Kiros, Y. K., Gebreegzabher, A., Tasew, G., Abdulkader, M., Abraha, H. E., Desta, A. A., Hailu, A., Tollera, G., Abdella, S., Tesema, M., Abate, E., Endarge, K. L., Hundie, T. G., Miteku, F. K., Urban, B. C., Schallig, H. H. D. F., … de Wit, T. F. R. (2021). Effect of co-infection with intestinal parasites on COVID-19 severity: A prospective observational cohort study. EClinicalMedicine, 39, 101054. https://doi.org/10.1016/j.eclinm.2021.101054

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Author’s affiliations

1WPLab, Inc., Durham, NC 27707, USA, 2Department of Pathology & Medical Biology, University Medical Center Groningen, Groningen, The Netherlands, 3Mekelle University College of Health Sciences, Mekelle, Ethiopia 4Amsterdam Institute of Global Health and Development, Department of Global Health, Amsterdam University Medical Center, Amsterdam, the Netherlands, 5Joep Lange Institute, Amsterdam, the Netherlands