There is likely not directly infectious replicating skin in a condition known as "COVID toes," and that’s important to reassure patients, said Christine Ko, MD, professor of dermatology and pathology at Yale University.
There is likely not directly infectious replicating skin in so-called COVID toes, and that’s important to reassure patients: that you’re not at risk for directly infecting others, said Christine Ko, MD, professor of dermatology and pathology at Yale University and a panelist on “What’s New in Dermatopathology,” presented at this year’s conference.
Can you tell us about COVID toes and detecting SARS-CoV-2 in various tissues?
COVID toes is also called perniosis. Or you could call it perniosis during the pandemic, because some experts, and I would include myself in this, I’m not sure that there’s true replicating virus in the skin that’s directly causing that lesion on the toe.
What it looks like is sort of a pink or sort of maybe purplish to maybe even gray or black in darker colored skin; discoloration almost or sometimes a little bit of swelling, sometimes the skin breaks down. And it mainly does affect the toes, which is why there’s that popular moniker “COVID toes,” but it can affect the fingers. And an important clue is that it can also affect other parts of the foot, like the heel, which are garden variety idiopathic perniosis, or perniosis associated with connective tissue diseases, that we did have as well before the pandemic ever happened. It doesn’t usually affect things like the back of the heel.
There are some clues clinically that can suggest to you that this is the entity associated with this pandemic. And I think what researchers, including myself, were curious about early on is whether there really is virus in the skin, that infectious virus. And our skin has that barrier on top of it for most of us, but when that skin breaks down, could that lesion transmit infection? Because that can happen. We know with things like chickenpox there are contact precautions for people with active lesions. It didn't seem like that would be the case, but interestingly, we did find positive staining of the virus spike protein with immunohistochemistry, which is a technique that specifically identifies protein in the skin. There’s an antibody that can bind to a specific protein, whatever it is, and gives you a signal.
The problem is that immunohistochemistry is not necessarily completely specific, and so even though it was a test designed to detect spike protein, there may be other proteins in the skin that are quite similar to spike that we just don’t know really what they are. And so it is always possible that that antibody is detecting another protein that's very similar, perhaps even another viral protein that we just didn’t ever really know to look for. And there is some suggestion from before the pandemic that perniosis—perniosis that happened way before COVID struck us—can maybe be a manifestation of a viral infection, even a later manifestation.
So with the question being, well, is there really a virus there, it was interesting that we found a spike protein signal, so maybe there really is spike protein, but when we looked for RNA for spike protein, it was not there; we could not detect it with a technique that was directed against spike RNA. And there are other papers that have used a technique that’s even more sensitive, where they're looking for just viral RNA, in general, of that SARS-CoV-2 virus directly in skin that’s showing a lesion, and it’s negative.
There was a really important JAMA Dermatology paper of about 31 patients, and they did that sensitive test—PCR, polymerase chain reaction, testing—of lesional skin and they did not find virus. It’s still small numbers, so that’s why I have a little bit of a caveat, but my feeling is that there is not directly infectious replicating skin in COVID toes. And I think that's important to reassure patients: that even if this is somehow related to COVID-19 infection, that it’s a late manifestation and you’re not at risk for directly infecting your family members or people who you’re coming into contact with.
Most of these patients developed lesions it seems at least 4 weeks out from any sort of systemic symptoms—if they had them. The majority of patients did not have any known kind of infection with COVID-19. And many of the patients, even when you look for antibodies or some sort of nasal pharyngeal active PCR at the time, they’re all negative—although a small minority are positive or have a very significant history of being exposed to someone with significant COVID-19 infection.
So there’s definitely some suggestion that this is related to the COVID-19 pandemic, so I think that moniker, “COVID toes” in that sense, yes, you can use that and it’s not really a misnomer. But in the sense of, is this truly active infection of the skin, I would say no.