In some people, genetic mutations can lead to increased production of type I interferons, proteins that are pivotal in responding to viral infections. COVID toes are likely a manifestation of this exaggerated protective response among patients who successfully control the virus and do not develop severe COVID-19.
Conversely, Arkin said, evidence indicates that gene mutations producing too few type I interferons may cause extreme susceptibility to respiratory viruses. This explains why some people become very ill later into the infection period as an attenuated, delayed response.
“It’s this idea that it’s not the virus that’s killing people; it’s the failed control of the virus,” Arkin said.Â
But, according to the American Association of Dermatology’s national registry, only about 15% of patients who developed COVID toes received positive antigen tests and about 30% produced antibodies, which Arkin said “leaves a big chunk of patients who still have no clear link.” This may be because patients develop COVID toes as a delayed response after the virus is no longer detectable, or because they fought the virus off so immediately and successfully that they never even created antibodies.
Researchers hope to more definitively link COVID toes to the virus. Arkin said the research has already detected strong Type I interferon responses in the skin, leading her to expect there will be similar findings in the blood: “The speculation is, if this is all Type I interferon … then it is a response to some viral exposure. And, of course, pinning the donkey with which is the most commonly circulating virus in Wisconsin, it’s COVID.”
