Your body is ground zero for a cellular arms race.
Your mitochondria, red blood cells and immune system rely on iron to function; so do invading viruses and bacteria. As your body evolves safeguards for this most critical resource, these safeguards select for invaders that can overcome them.
"Iron is physiologically useful in catalyzing reactions, such as binding oxygen, because it both donates and accepts electrons," explained Binghamton University Associate Professor of Anthropology Katherine Wander, the first author of a recent paper on the topic.
"Iron nutrition and COVID-19 among Nigerian healthcare workers" appeared in the journal Evolution, Medicine, and Public Health. Wander's 34 co-authors include personnel from Nigerian hospitals and universities; Binghamton doctoral students Meg Gauck in anthropology and Zifan Huang, who assisted in data curation and analysis; Mei-Hsiu Che, Binghamton's director of Statistical Consulting Services; and Associate Professor of Africana Studies Titilayo Okoror, who aided in funding acquisition and project administration.
COVID-19 represented an intriguing opportunity for study. As a novel virus, it had less opportunity to adapt to human physiology - and less time in the evolutionary arms race.
The study focused on healthcare workers in four Nigerian hospitals working in coronavirus wards during the pandemic's Delta wave. Most of them had Astra Zeneca vaccinations at this point, Wander said.
The war for iron
The body uses iron in multiple ways, from immune function to catalyzing reactions in mitochondria, which produce cellular energy in the form of adenosine triphosphate (ATP).
Iron, famously, is what gives red blood cells their color. Red blood cells use a protein called hemoglobin to transport oxygen. Hemoglobin, in turn, is made of smaller proteins known as heme, which contain an iron molecule that binds and transports the oxygen.
"Our pathogens need iron for the same reasons," Wander explained. "A virus hijacks the cellular machinery to make more virus. Often, viruses increase the cellular uptake of iron."
Simply put, naturally high levels of iron offer needed resources for your body's cells, but it also becomes available to pathogens, promoting their spread. As a result, we have evolved layered, overlapping mechanisms to keep iron under control, while pathogens continually evolve ways to overcome these obstacles.
In an evolutionary sense, the pathogens have the advantage.
"Even in the best of circumstances, our immune system can't adapt as fast as something with a generation time of 20 minutes," said Wander, referring to iron sequestration mechanisms. "Bacteria and viruses are able to turn over new generations so quickly that their evolution just happens faster."
In biological anthropology, the optimal iron hypothesis refers to a purported "sweet spot" that reduces susceptibility to infection, while mostly meeting the body's iron needs.
The research in Nigeria showed that individuals with plentiful iron in their system did have a higher risk of catching COVID, as well as people who had anemia. But mild or moderate iron deficiency, however, didn't seem to protect against infection in and of itself.
The case study of COVID-19 suggests that even very early in the arms race - when an infectious disease is emerging and still very new to humans - iron nutrition tradeoffs are in play.
"Any additional increment of iron is going to come with both potential benefits in terms of immune defense and potential risk from an infectious agent," Wander said. "The trade-off is always there, but the optimal level is going to shift depending on the infectious disease environment."
This tradeoff is potentially one of the reasons why iron deficiency is common even in otherwise well-nourished populations, particularly among women.
The body tends to conserve iron, recouping 80% of the iron contained in senescent blood cells. We're not, however, particularly efficient at absorbing iron, and dietary factors can interfere with this process.
"Humans seem to be vulnerable to iron deficiency, and we try to solve that problem by helping people improve their iron intake and iron absorption," Wander said. "It's hard to do."
