The most common symptoms of COVID-19 are fever, dry cough and loss of taste and smell. Other common signs include headache, muscle and joint pain, nasal congestion and fatigue.
A less common symptom is rashes of various forms. These have been reported more slowly, in part because of the wide variety that has occurred in patients with COVID-19, making it more difficult to establish a consistent correlation.
However, it is important to know how COVID-19 affects the skin. A recent study found that for 17% of COVID-19 patients with multiple symptoms, rash was the first symptom to occur, while for 21% of patients, rash was their only symptom.
The ability to identify the effects of COVID-19 on the skin may allow cases to be detected earlier – or even taken up entirely in people who are otherwise asymptomatic. This could help limit transmission.
With this in mind, here are the four main types of skin changes that need to be considered and the possible reasons for them.
Chilblain-like lesions
These are red, swollen or blistered skin lesions that mainly affect the toes and soles, colloquially known as “COVID toes”. Within one to two weeks, the lesions will become even more discolored and flatten, and after that they will resolve spontaneously without treatment.
A substantial number of these lesions were observed primarily in adolescents and young adults with no or only mild symptoms of COVID-19. They represent the majority of skin problems associated with the virus. In two international reports of various types of suspected COVID-related skin conditions, approximately 60% of patients with skin conditions reported these lesions.
However, given that these lesions correlate with a mild illness, many of the patients with them in these studies did not qualify for a COVID-19 test at that time, and 55% were otherwise asymptomatic.
So, while the rapid growth of these lesions during the pandemic suggests that they are associated with COVID-19, direct confirmation of this has not been established. It may be caused by another related factor.
Exactly when they appear is also somewhat unclear. In a study that looked at 26 patients with suspected COVID-related skin changes, 73 percent had child-like lesions. None of the patients showed respiratory symptoms and all were COVID-negative at the onset of the lesions. One explanation is that these lesions appear only after a long delay – up to 30 days after infection.
The cause of these injuries has been debated. A possible culprit could be type 1 interferons, proteins that regulate the antiviral properties of the immune system.
The theory is that high production of these interferons could lead to the rapid elimination of coronavirus patients, but can cause damage to blood vessels and increased inflammation. This would explain the coincidence of mild or non-existent disease, negative tests and skin damage.
Another theory concerns ACE2, the molecule that the coronavirus uses to get inside cells. It is present on many types of cells, including those in the sweat glands, which are common on the palms of the hands and the soles of the feet. This could make these areas particularly vulnerable to damage from the virus.
Or it could be that the damage to the blood vessels, caused by either the immune response or the virus, can lead to cell death and multiple mini blood clots in the toes.
Maculopapular rash
This term describes both flat and high areas of discolored skin. A study of 375 patients in Spain found that 47% of patients with COVID-related skin changes had this type of rash.
These have been associated with more severe symptoms of COVID-19 and have been found mainly in the trunk in middle-aged to elderly patients. They tended to last 7-18 days, appearing 20-36 days after infection.
One suggested cause is that the body’s immune system goes into excess. In some patients, a hyperinflammatory phase occurs 7-10 days after infection, leading to tissue damage and, potentially, more severe disease and death.
Hives
Also known as hives, these are high itchy areas of the skin. In a study involving four hospitals in China and Italy, 26% of COVID-19 patients complained of skin changes with hives.
Urticaria precedes or is present at the same time as other symptoms, making them useful for diagnosis. They are more common among middle-aged patients and are associated with more severe diseases. Viral infections are a known trigger of urticaria because they cause cell breakdown and the release of histamine through a cascade of reactions in the immune system.
However, it is important to remember that hives are also a notable side effect of many drugs that have been used to treat COVID-19, such as corticosteroids and remdesevir.
Bladder lesions
These are clear bags filled with fluid under the skin, similar to those seen in chickenpox. They are less common compared to the above skin conditions: in the aforementioned Spanish study on skin changes associated with COVID-19, only 9% of patients had these blisters.
However, these are thought to be a more specific indication of someone having COVID-19 than those already listed and are therefore more useful for diagnosis. It appears to occur in patients with mild illness about 14 days after infection.
They are believed to be caused by prolonged inflammation, with antibodies attacking the skin and damaging its layers, leading to bags full of fluid. 
Vassilios Vassiliou, Senior Clinical Lecturer in Cardiovascular Medicine, University of East Anglia and Subothini Sara Selvendran, Visiting Researcher in Medicine, University of East Anglia.
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