Low iron mitigates viral survival: insights from evolution, genetics, and pandemics\u2014a review of current hypothesis

Rahma Menshawey,Esraa Menshawey,Ayman H K Alserr,Antoine Fakhry Abdelmassih

doi:10.1186/s43042-020-00114-z

Rahma Menshawey, Esraa Menshawey + Show 2 more

Open Access

https://doi.org/10.1186/s43042-020-00114-z

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Abstract

BackgroundUpon re-examination of our human history, evolutionary perspectives, and genetics, a prevailing iron deficiency phenotype appears to have evolved to protect the human race from extinction.BodyIn this review, we summarize the evolutionary and genetic perspectives pointing towards the hypothesis that low iron mitigates infection. The presence of infection promotes the generation of resistance alleles, and there are some evolutionary and genetic clues that suggest the presence of an iron deficiency phenotype that may have developed to protect against infection. Examples include the relative paucity of iron overload genes given the essential role of iron, as well as the persistence of iron deficiency among populations in spite of public health efforts to treat it. Additional examination of geographic areas with severe iron deficiency in the setting of pandemics including H1N1, SARS, and COVID-19 reveals that areas with higher prevalence of iron deficiency are less affected. RNA viruses have several evolutionary adaptations which suggest their absolute need for iron, and this dependency may be exploited during treatment.ConclusionRNA viruses pose a unique challenge to modern healthcare, with an average of 2–3 new pathogens being discovered yearly. Their overarching requirements for iron, along with human evolutionary and genetic adaptations which favored an iron deficiency phenotype, ultimately suggest the potential need for iron control in these infections.

Highlights

ribonucleic acid (RNA) viruses pose a unique challenge to modern healthcare, with an average of 2–3 new pathogens being discovered yearly
This study suggests that the presence of concurrent malnutrition disorders limit the effectiveness of iron therapy in the setting of iron deficiency anemia (IDA), while other studies suggest that the resistance to iron supplementation in the setting of anemia may be due to genetic variations
The insight provided by evolutionary and genetic perspectives, points towards an iron deficiency phenotype that has prevailed throughout generations, providing protection against acute infection

Summary

Conclusion

The insight provided by evolutionary and genetic perspectives, points towards an iron deficiency phenotype that has prevailed throughout generations, providing protection against acute infection. Evidence that point to an overarching role of iron in COVID-19 infection includes hyperferritinemia in severe cases, similarities between COVID-19 and hyperferritinemia syndromes, and hepcidin overexpression that may be responsible for the increased risk of disease in diabetic, obese, and elderly patients Given this understanding, targeting iron from a therapeutic stand point may prove decisive as part of adjuvant therapy against such viruses; more robust evidence is needed. If low iron mitigates infection, the areas with high iron deficiency anemia prevalence may be protected against some types of infection, such as Sub-Saharan Africa To enhance this theory, further investigations are needed to determine the genetic variants responsible for iron imbalance among susceptible populations.

Background

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Findings

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