As more COVID-19 patients are seen across the world and their individual cases are analyzed, the longer the list of symptoms associated with novel coronavirus seems to become.

According to the Washington Post, another symptom of the new virus may be 'frostbite toes.'

A dermatologist at Massachusetts General Hospital in Boston, Esther Freeman, reports getting multiple calls about odd frostbite-like patches showing up on people’s toes.

Though the rash itself was harmless, some patients complained that it was accompanied by a burning sensation.

But what triggered Freeman's curiosity is that many of the patients with this rash also tested positive for COVID-19.

“My inbox and my telemedicine clinic are full of just toes. It’s all about toes. I have never seen so many toes,” Freeman said.

The curious phenomenon has also caught the interest of researchers in hot zones such as France, Italy and China. But the reports had been mostly limited to individual case studies and first-person observations, making it difficult to determine what these rashes mean, why they are occurring and how they are linked to the virus.

Now a U.S.-based group is preparing to publish the first in-depth look at covid-19’s dermatologic effects, based on a registry of nearly 300 patients confirmed or suspected of having the virus. The report, expected out as soon as this week, offers some tantalizing clues about the pathogen and its wildly different effects on different people.

Four months into the battle with the novel coronavirus, the paper is part of a flood of scientific evidence that is challenging early assumptions that covid-19 primarily affects the lungs. While the majority of cases turn out to be mild and may involve no symptoms at all, evidence has proven that infection can result in devastating injury to the kidneys, heart, and other major organs.

And in the same way the first sign of infection for some may be loss of smell and taste — those are among the six new covid-19 symptoms the Centers for Disease Control and Prevention added to its list Monday — the toe rashes may be an early marker of disease, or possibly one that it has resolved and passed.

One of the clearest findings of the new paper is that most patients with “COVID toes” were asymptomatic or had only mild symptoms. Another is their age. Nearly all were children or adults in their 20s and 30s — a group that as a whole tends to have a less severe bodily response to the disease than their older counterparts.

Freeman, a Harvard Medical School researcher who led the analysis in collaboration with the American Academy of Dermatology, said the information should be comforting to those who have seen the lesions on themselves or loved ones.

“Most of the patients were young, healthy and had a benign clinical course,” she said.

“The message to the public is not to panic,” she added. “I don’t want people to think if they are having purple spots on their toes that they are going to end up on a ventilator in the ICU. That is not what we are seeing in the data.”

Freeman said that while her team is still analyzing information about other types of rashes, she feels it’s important for people to be aware because they “are potentially infectious and might have no idea they are infected.” She urged those who notice such lesions to talk to a health-care professional to see if there may be other explanations.

One of the earliest report of issues in toes came in early April, when a French dermatology group warned of “pseudo-frostbite” of the extremities and transient hives, and urged patients with such problems to consult a dermatologist. 

“We alert the population and the medical profession to detect these potentially contagious patients — who may not necessarily have respiratory signs — as soon as possible,” they wrote.

Then on April 18, a report in the Journal of the American Academy of Dermatology detailed purplish lesions on the feet of a 23-year-old student in Belgium. He had a dry cough and a low-grade fever and tested positive for covid-19, but was otherwise healthy. The researchers theorized that the lesions may “portend an indolent course and a good prognosis.”

Viral rashes themselves are not unusual. Changes in the skin — the body’s largest organ — are often one of the most obvious indicators that something is amiss. Measles produces itchy flat spots; coxsackie, painful sores in the hands, feet and mouth; and dengue fever, what has been described as “islands of white in a sea of red” on the face.

But the location of the rash on the toes, and sometimes fingers too, has puzzled researchers.

This type of rash, called pernio or chilblains, usually occurs in the dead of winter because of exposure to cold, such as when a person is slogging in freezing rain in wet socks. But covid-19 patients are getting it in springtime. Doctors also typically see the rash in people who work as florists or in warehouses that are not temperature-controlled — not in children, as is happening now.

“The truth is nobody knows why this is happening and why it’s happening in the toes and fingers,” said Ebbing Lautenbach, chief of the division of infectious diseases at the University of Pennsylvania’s Perelman School of Medicine.

One theory is that it may be related to inflammation and blood-clotting complications, he said, which more and more doctors suspect are a cause of some COVID-19 deaths.

“As you get away from the core of the body out to the periphery, the blood vessels get smaller, so they are more susceptible to inflammation and clotting,” Lautenbach explained.

In the case of the 23-year-old student in Belgium, researcher Curtis Thompson said a biopsy showed inflammation in the cells in the location of the rash that resulted in attacks to the surface of the skin’s dermis, the inner of the two main layers of skin. He said it looked nearly identical to what he’s seen in patients with lupus, an autoimmune disease that causes inflammation and pain because the immune system attacks healthy tissue.

“You could take these biopsies and put them in a textbook under the lupus chapter,” said Thompson, an affiliate professor of dermatology and pathology at Oregon Health & Science University.

As a result, he believes the rashes are a sign that the body’s natural defense mechanisms are at work. But unlike lupus, for which there is no cure, the suspected COVID-19 rashes have come and gone within days or weeks in the patients he’s seen.