© Sebastian Gollnow/Picture Alliance via Getty ImagesA doctor conducts a Covid-19 test on a teacher. Researchers are still finding new symptoms of the disease.
It's been more than a year since Covid-19 landed in the United States. And the once-perplexing array of symptoms like coughing, fever, shortness of breath, and loss of taste and smell are now very familiar to doctors around the country.
The range of possibilities when someone shows up to a doctor's office with new respiratory symptoms "is very, very narrow these days," said Anish Mehta, medical director for clinical quality and virtual health at Eden Health, and an assistant clinical professor of medicine at the Icahn School of Medicine at Mount Sinai. "It's probably Covid if you have fever and you're coughing, or if you have a fever and feel muscles aches."
Medical researchers have also learned more about how a Covid-19 infection can ripple through the circulatory, nervous, and immune systems with symptoms like rashes, blood clots, strokes, and even foot lesions dubbed "Covid toes." They're also more familiar with the more than 10 percent of Covid survivors who are reporting long-term symptoms, including difficulty thinking and focusing, heart palpitations, hair loss, and mood swings.
Yet even now researchers are finding new symptoms. Tim Spector, a professor of molecular epidemiology at King's College London, has been studying Covid-19 throughout the pandemic through a Covid-19 Symptom Study smartphone app. He recently started receiving reports of mouth ulcers and something he calls Covid tongue - a fuzzy yellow-white coating on the tongue.
"It came about because people sent me images of their tongue," said Spector. "I posted them and then people started ... realizing that's what they had originally when they had Covid. It's a strange phenomenon that no doctor thought was related."
Though cases and hospitalizations are falling, and multiple Covid-19 vaccines are rolling out, the SARS-CoV-2 virus that causes Covid-19 is still spreading, and new variants are threatening to undo some of the progress made during the pandemic. The more the virus spreads, the more likely it is to acquire new mutations. Changes in symptoms could be a warning sign of these changes to the virus. So doctors have to remain on their toes.
"I think the lesson is unusual symptoms can come out of the blue with no clear explanation," said Andrew Chan, a professor of immunology and infectious disease at the Harvard T.H. Chan School of Public Health, who collaborated with Spector on the symptom study app. "It has to be on every health care provider's mind."
The list of Covid-19 symptoms is still getting longer
The fact that Covid-19 has spread so widely, with 115 million cases worldwide to date, means the disease has had opportunities to affect people under a variety of circumstances including preexisiting health conditions, age, nutrition, living standards, and access to health care. How Covid-19 interacts with these variables is part of why there are so many different symptoms.
According to the Centers for Disease Control and Prevention, the most common signs of Covid-19 are:
- Fever or chills
- Cough
- Shortness of breath or difficulty breathing
- Fatigue
- New loss of taste or smell
- Headache
- Muscle or body aches
- Diarrhea
- Sore throat
- Congestion or runny nose
- Nausea or vomiting
- Diarrhea
It's helpful to think of the progression of Covid-19 in stages. During the early phase of the disease, it's the virus itself that causes the most damage, leading to many of the respiratory symptoms like a loss of taste or smell, which remains one of the most predictive symptoms. As the disease progresses, the immune system's response becomes the dominant factor, leading to effects like fever, chills, and inflammation. Once the virus fades away, damage from the virus and the immune response can linger.
For instance, Covid-19 can lead to abnormal blood clotting. Those clots can then choke off blood vessels, impairing the function of other organs like the liver or kidneys. Some of these effects can take weeks to manifest.
Another factor to consider is that Covid-19 symptoms can group together in clusters, which can signal the prognosis for the disease. In a preprint paper using data from the Covid-19 symptom tracking app, researchers identified six distinct clusters of symptoms for Covid-19. For instance, patients who experienced respiratory symptoms like sore throat and coughing alongside gastrointestinal symptoms like diarrhea and abdominal pain were far more likely to end up hospitalized than Covid-19 patients who didn't have gastrointestinal problems.
Clusters are also emerging as a warning sign of long Covid. "We've seen that people who present with fatigue, headache, shortness of breath, loss of smell - that sort of cluster of symptoms in particular seems to be associated with a higher likelihood of developing long Covid," Chan said.
Scientists are still trying to figure out whether long Covid is due to the virus itself, other opportunistic infections, or latent underlying conditions exacerbated by the disease. "The underlying biology of why those things have been triggered by a virus is not clear," Chan said. Nonetheless, health officials are now concerned that these long-Covid symptoms could be a massive knock-on health crisis.
"I fear that some people who have had these effects who are already three or four months out may not be on a path to get better in a few more months," Francis Collins, director of the National Institutes of Health, told NBC News on March 1. "When you consider we know 28 million people in the United States have had Covid, if even 1 percent of them have chronic, long-term consequences, that's a whole lot of people."
Yet at the same time, there remain people who get infected and don't experience any symptoms at all but can still spread the virus. Estimates vary, but researchers suspect that between 20 and 50 percent of SARS-CoV-2 infections don't produce symptoms and lead to disease.
So while researchers have a better grasp of the disease now, there is still much to learn. And as the disease continues spreading and mutating, researchers worry that it can start to present in unexpected ways.
So far, people infected with the new variants have similar Covid-19 symptoms to older variants
It's rare, but researchers have documented several instances of people becoming reinfected with SARS-CoV-2. For the most part, the second round of infection results in milder symptoms than the first. But several people have become more severely ill the second time, and some have died.
The new variants of the virus that are rapidly spreading could increase the chances of this happening. Already, some of the variants have been shown to be more transmissible and likely more deadly. In laboratory studies, antibodies produced to counter earlier versions of the SARS-CoV-2 virus were less effective against some variants, like the B.1.351 variant first found in South Africa.
That means someone who shrugged off an earlier bout with Covid-19 could later experience a more dangerous course of the illness. Some variants could also make Covid-19 vaccines less effective at preventing disease.
As for how the variants present, right now they show up in similar ways to earlier versions of the virus. "From what we can tell from the work that we've done through the Covid symptom study, we haven't seen tremendously striking differences in terms of the symptoms that people present with," Chan said.
A survey in the United Kingdom found that the B.1.1.7 variant led to some subtle changes in symptoms. "People testing positive compatible with the new UK variant were more likely to report any symptoms and the classic symptoms, but were less likely to report loss of taste and smell," according to the UK Office for National Statistics.
But the US isn't conducting enough genetic surveillance to readily identify new mutations in the virus as they arise. A sudden change in symptoms may end up being the warning sign that another new variant has arrived. And even more symptoms that doctors didn't previously appreciate could still crop up.
"It just tells you we need to be humble and realize we know very little about this virus and keep an open mind," Spector said.