When the coronavirus pandemic first emerged, public health officials told the world to watch out for its telltale symptoms: fever, dry cough and shortness of breath. But as the virus has spread across the globe, researchers have developed a more nuanced picture of how symptoms of infection can manifest themselves, especially in milder cases.

We're getting a "better understanding of how these symptoms express in the general population and not necessarily in hospitalized patients," which is whom most of the earlier studies from China looked at. "So it's a bit of a bigger picture," says Charitini Stavropoulou, an associate professor in health services research at City, University of London in the U.K., who led an analysis of known symptoms in milder cases as part of a collaboration with Oxford University.

Some of these symptoms, such as loss of smell or taste, are highly distinctive and a strong indicator of infection. Others, like headaches, chills or sore throat, are common to lots of illnesses. So how do you know when a symptom is cause to seek medical advice or testing? We asked doctors and public health and infectious disease researchers for their insights.

THE STANDARD 3

Fever: Some patients can experience fevers that last for days, while others might see their temperature go up and down, with peaks often occurring in the evening, says Dr. David Aronoff, chief of the Division of Infectious Diseases at Vanderbilt University Medical Center. "I think if someone has a fever, regardless of how long it's lasting, unless they can clearly attribute it to something else, that's a very reasonable symptom to seek an evaluation for," he says.

Stavropoulou's systematic review of the medical literature found that fever was reported in 82% to 87% of mild to moderate cases.

Dry cough: Cough was the second most common symptom after fever, though "coughing was not always there," Stavropoulou notes. "So while we think it's a main symptom, it appears only two out of three times for patients with COVID-19."

That said, cough remains a "very, very common symptom of the pneumonia that the virus can cause," says Aronoff. Given this fact, "if someone has a new cough or a new shortness of breath that's cropped up in the last three days or so, they should definitely get tested."

Shortness of breath: Stavropoulou's review found that this symptom occurs more frequently in severe cases "and indeed, in some studies, was a marker of severe disease." The two largest studies she looked at found that shortness of breath occurred in fewer than 8% of milder cases.

THE NEW 6 FROM THE CDC:

Chills/repeated shaking with chills: The chills generally precede a fever, though people don't always perceive when their temperature has spiked, Aronoff says. Sometimes, those chills can be accompanied by shaking, since shivering is our bodies' way of generating heat and raising our temperature, he says.

Muscle pain: Nearly 15% of COVID-19 patients experience muscle pain, according to a report published by the World Health Organization in February that analyzed nearly 56,000 confirmed cases in China. But that's hardly unique to this disease: Lots of viral infections can cause muscle aches and pains, which can result from an inflammatory response to a virus.

"I think all of us who have had the winter cold or flu have had experience with muscle pain, headache, sore throat," notes Aronoff. Given that we're no longer in the typical cold and flu season, if you're experiencing muscle pains and other flu-like symptoms, "we know that those can be associated with COVID-19," he says. "And it is very reasonable to get people thinking, you know, maybe I should get tested."

He added: "I would also include new-onset fatigue, out of proportion to what a patient would expect to be experiencing under whatever circumstances they are [in]," as a symptom.

However, fatigue on its own is not very predictive of disease, because it is also frequently reported by people who don't test positive, says Claire Steves, a geriatrician and senior lecturer at King's College London. She's one of the lead researchers on the COVID Symptom Tracker, an app-based project that has so far recruited 3 million people across the U.K. to log any symptoms — even if they are not feeling sick. Researchers can use data from those who are eventually diagnosed with COVID-19 as an early radar on how symptoms develop in the population. (The COVID Symptom Tracker is now recruiting people in the U.S. to sign up as well.)

Steves' research is finding that certain symptoms tend to cluster together in people who test positive. For instance, fitter people in the 20-70 age range who experience loss of smell often also experience fatigue, and they tend to have a milder course of the disease, she says.

Headache: Headaches are a common experience for many adults. On its own, a headache should probably not be cause for alarm, especially if it behaves like other headaches you've experienced, says Aronoff.

"If somebody is only going to use headache as a trigger to go get tested for COVID[-19], that headache should be something that either is a headache that's new for them or that is sticking around a bit longer than they are used to," he says. "Or it's associated with another symptom that may also be subtle, like fatigue or feeling kind of worn out" — especially if there's no good reason for the tiredness.

In fact, Steves says research out of the COVID Symptom Tracker suggests that headache "is an important symptom" seen early on in the course of the disease and it commonly occurs alongside other symptoms.

Sore throat: "We're seeing sore throat in COVID-19 patients," says Aronoff. "But it's what I would say [is] a minor symptom" — one that's common to lots of other ailments.

Loss of taste or smell: This symptom has emerged as a strong indicator of infection — one distinctive enough that it alone should be cause to seek testing, says Dr. Carol Yan, an otolaryngologist and head and neck surgeon at UC San Diego Health.

If someone is experiencing this symptom, "I would tell them that they should consider self-quarantining themselves and contacting their health care providers," says Yan. Most people who experience loss of smell or taste also have other symptoms, commonly fever, fatigue and malaise, she says. "But there's certainly a subset of people that we know have only smell and taste loss and no other symptoms" who ultimately test positive.

Yan's research has found that about 7 out of 10 patients reported an acute loss of sense of smell or taste at the time of their diagnosis.

Similar findings have emerged from the COVID Symptom Tracker. Among fit and healthy people ages 20 to 70, "the loss of sense of smell is a really good marker" of infection, Steves says.

In fact, this symptom is seen as such a strong indicator of infection that patients at UC San Diego Health are now routinely asked not just if they have a cough or fever but also if they're experiencing a loss of smell or taste, says Yan. "It's really being used as a good screening question and in helping triage patients."

The good news is that both Yan and Steves have found that people who lose their sense of smell or taste tend to experience a milder course of the disease. Yan says patients generally recover these senses in two to four weeks on average.

OTHER POTENTIAL RED FLAGS

Confusion and gastrointestinal issues: Stavropoulou's review of the medical literature found that, in most studies, gastrointestinal issues were reported in fewer than 10% of mild cases of COVID-19.

But Steves says emerging data from the COVID Symptom Tracker suggest that problems like diarrhea, nausea and abdominal pain tend to be more prominent in the frail elderly — people who are over 70 and need help to get around. Acute confusion also seems to be an important symptom in this group, she says.

"Older and frailer and more co-morbid people" — those with underlying conditions such as heart disease, diabetes or obesity — "tend to be getting this cluster of abdominal symptoms and delirium symptoms and headache as well," Steves says.

She says it's important for caregivers to recognize that these symptoms in the frail elderly could be indicative of COVID-19, particularly in situations like nursing homes, "because that's where spread could occur."

AND THEN THERE'S THIS ...

"COVID toes" and other skin manifestations: Dermatologists are now reporting that certain skin conditions appear to be emerging as symptoms of infection in milder cases. Among the most common — and striking — is "COVID toes," a condition resembling chilblains, or pernio, on the feet or toes, says Dr. Esther Freeman, director of global health dermatology at Massachusetts General Hospital and director of the international Dermatology COVID-19 Registry. The registry has received more than 400 reports from dermatologists in 21 countries, and a little under half are cases of COVID toes, she says.

Normally with chilblains, "you would see pink, red or purple lesions on the toes or sometimes on the hands," Freeman says. "That's often accompanied by swelling and can also be accompanied by a burning, itching or tender sensation," she says.

Chilblains are caused by inflammation in the small blood vessels of the skin, usually in reaction to colder temperatures or damp weather, Freeman says. "So, for example, spending a lot of time outside in wet socks could do it."

What's unusual is that during the coronavirus pandemic, "we're seeing patients who are living in warm climates or patients who have been sheltering inside and staying warm developing these lesions for the first time," she says.

"I have seen more toe consults in the past two weeks than I have in my entire prior career combined," Freeman says.

She says some patients develop COVID toes early on, along with other symptoms such as fever or cough. Others develop the condition well after their other symptoms have passed, almost like a post-viral response. And a third category of patients seems to develop COVID toes as the sole symptom.

Other skin conditions reported include hives and morbilliform, a measles-like rash on the chest, back, arms or legs. Freeman notes that viruses — for example, those that cause measles or chickenpox — often cause rashes, so dermatologists were expecting that with the coronavirus. But the toe manifestations were surprising.

While data are still emerging, Freeman says that in her opinion, dermatologic symptoms, such as COVID toes, should be considered as criteria for testing. But if you're having these symptoms, she says, "Please don't panic. Most of our patients who are developing these COVID toes are doing extremely well and are able to recover fully at home."

"I think it's also important to know that the purple lesions will go away on their own," she adds.

Copyright 2020 NPR. To see more, visit https://www.npr.org.

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