Dr. Esther Freeman discusses the complexities of COVID antibodies and what it means to the clinician.
Esther Freeman, MD, PhD, is Director of Global Health Dermatology at Massachusetts General Hospital, Harvard Medical School, Chair of Clinical Guidelines at the American Academy of Dermatology (AAD), and a Member of the AAD Dermatology COVID-19 Task Force. She directs the COVID-19 Dermatology Registry, an international effort supported by the American Academy of Dermatology and the International League of Dermatological Societies (ILDS). The registry has over 1000 cases from 40 countries.
“I think dermatologists have a key role in really understanding host immune response and in understanding viral control, and in some ways things like COVID toes and other skin manifestations have given us a key by which we can do that,” says Esther Freeman, MD, PhD.
Very few patients who present with COVID toes test PCR positive for the virus in the nose, but it doesn’t mean they didn’t have COVID. Considered post acute sequela of COVID-19, it is not surprising that most patients who present with pernio won’t have a PCR positive result, says Dr. Freeman.
“This actually makes sense because we’ve learned over time that pernio, or chilblains, start about one to four weeks after acute infection. So this is not something that shows up the moment you’re infected. We know from our data analysis and the registry that only about 15% of patients when they show up with pernio will be PCR positive, even in the setting of SARS-CoV-2.”
Early in the pandemic, antibody data were generated from hospitalized COVID patients, and there was an expectation that COVID-19 patients overall would have robust antibody responses. But not everyone makes the same antibodies to the COVID-19 virus, if they make antibodies at all.
“It’s possible you could have mild COVID-19 and make a big antibody response,” says Dr. Freeman, “But we also see a lot of patients who we know—even with PCR proof—had SARS-CoV-2, and they actually just don’t mount a significant antibody response. And this is particularly true for our patients with mild COVID-19.”
According to Dr. Freeman, patients with COVID toes may make a robust interferon alpha (IFN-⍺) response, similar to a type I genetic interferonopathy.
“The interferon alpha response isn’t necessarily a bad thing. Younger patients tend to have a more robust host immune response and likely make more interferon alpha, and we know that interferon alpha is actually helpful for controlling the virus.”
She notes the contrast of COVID toes patients who tend to be younger with good outcomes, with patients who have severe COVID-19 and very low IFN-⍺ levels.
“Now this gets even more complicated because there’s a couple other things at play. We know now that there’s actually these robust T cell responses. So some people are not necessarily relying on their antibody response to control the virus they’re relying on their T cell response, and that’s not something that’s measured in the antibody tests.”
The other complexity in patients with pernio who have a robust IFN-⍺ response is that they don’t make particularly high antibody levels. If they do, they make IGA antibodies which are not routinely tested.
“I think that it’s very tempting to have your patient in front of you and you do an antibody test, and it comes back negative. And the temptation is to interpret that as my patient did not have COVID-19. And that’s actually not really the interpretation.”
The correct interpretation, she says, is, when you tested your patient for IgM or IgG, he or she was making insufficient IgM/IgG at that time.
“You have to understand those tests are looking for something very, very specific,” says Dr. Freeman. “Your patient may not be making those antibodies, but that doesn’t mean they didn’t have COVID-19. I think it’s just important for people to realize that.”
