If there’s one symptom that’s become synonymous with COVID-19, it’s the cough. It’s not surprising, then, that many of us think of COVID-19 as strictly a respiratory illness: One that infects your lungs and airways and causes, among other symptoms, a cough. So why, then, are some people with COVID-19 reportedly having strokes or suffering heart failure? Why do others lose their sense of smell, experience confusion, or have sore, itchy toes? If this is a respiratory infection, why are so many other parts of the body affected?
Experts say the novel coronavirus is not some kind of all-powerful superbug; the wide range of symptoms and complications experienced by COVID-19 patients are also found in other kinds of infections. But whether these reactions are caused by the virus itself or the body’s immune response to it is still a mystery.
What we know
When it comes to provoking a wide range of reactions in the human body, the novel coronavirus is not unique. Viruses both common (like influenza) and rare (like Ebola) can cause reactions beyond the typical symptoms. So these early reports showing an association between COVID-19 and a range of symptoms beyond the classic fever and cough aren’t that surprising.
“Headaches, dizziness, confusion — viral infections or pneumonia lead to those kinds of symptoms in the hospital all the time,” said Dr. S. Andrew Josephson, chair of the department of neurology at the University of California San Francisco.
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Seasonal flu, for example, is associated with an increased risk of heart attacks and stroke, according to the Centers for Disease Control and Prevention. One study published in the New England Journal of Medicine in 2018 found that the risk of heart attack was six times higher for people who had tested positive for the flu in the last seven days. Another study published that year found a link between influenza-like illnesses and an increased risk of stroke.
Or take a look at Ebola. It’s most commonly associated with bleeding and hemorrhaging, but the virus can also cause gastrointestinal issues like vomiting.
Cytokine storms, a condition where an overabundance of immune cells triggers widespread inflammation, have been cropping up in some of the sickest coronavirus patients, but they aren’t unique to severe cases of COVID-19. They can be triggered by other pathogens, including ones that typically don’t cause severe illness, like the flu.
“Cytokine storm syndromes kill people, children and adults, every day in ICUs all over the globe,” said Dr. Randy Cron, a pediatrician at the University of Alabama at Birmingham and author of a textbook about cytokine storms. “Many of them are associated with viruses, and there are certain viruses that are much more likely to trigger it than others. But there are probably over 100 different organisms, including bacterial, protozoal and fungal, that have been associated with the cytokine storm. They occur all the time.”
A number of factors contribute to determining what kind of symptoms an infection causes. The route of transmission, the viral load (how much of the virus a person has reproducing inside them), which strain of the virus the person caught, and the genetics and predispositions of the individual who is sick can all influence which symptoms emerge, according to Angela Rasmussen, a virologist at Columbia University who specializes in infectious diseases.
Rasmussen also said that some of these COVID-19 symptoms may be rare, but because the disease has spread so widely and is being given such close attention, doctors and researchers are much more likely to see and catalogue even the least common types of cases.
“A lot of this has to do with the number of people that have been infected,” Rasmussen said. “When you have a smaller subset of patients, you might not see all of these broad, different presentations of the clinical disease.”
What we don’t know (and how we figure it out)
We know that viruses can cause a broad spectrum of reactions in the human body, so it’s totally possible that the novel coronavirus does as well. But there’s a lot we don’t know, such as whether all the symptoms that have been reported in patients with the new virus are actually related to COVID-19, how common those symptoms are, and whether the virus itself is causing them — by, for example, infecting heart tissue — or if the body’s immune response is what’s leading to the complications.
Neurological symptoms like brain fog and dizziness, for example, may be caused by inflammation due to the immune system trying to fight off the infection, according to Josephson.
“When you have inflammation everywhere in the body, the brain doesn’t work so well,” he said. “We don’t understand all of these mechanisms, but we do know this is a very common observation when people get sick.”
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But there’s also a chance these symptoms are caused by the virus managing to infect the brain and damage cells. And knowing whether the cause is the body or the virus tells doctors not only what the potential treatment options are but also what the patient’s prognosis is, Josephson explained.
“If most of the effects are simply due to the body having all this inflammation, then when that inflammation goes down, the nervous system is going to recover,” Josephson said. “But if it’s due to an actual viral invasion of the brain and nerve cells are dying, that may be a very different story in terms of long-term prognosis.”
The only way we’ll know for sure, Josephson said, is through research, such as studying tissue samples from autopsies to look for evidence that the virus caused damage directly or observing groups of patients who had specific responses (like a heart attack) and comparing them to patients who didn’t.
Animal studies may also provide some answers, according to Rasmussen. (She told me ferrets are particularly useful because they have a similar respiratory system to humans.) By running experiments in animals, researchers can start to pinpoint what’s different about people who have a particular outcome versus those that don’t. A paper published earlier this year and co-authored by Rasmussen, for example, used a genetically diverse pool of mice and gave them Ebola to see how genes affected the severity of the infection and what kind of symptoms emerged.
“We looked at gene expression and linked that to the ultimate outcome,” Rasmussen said. “Using the features we found in the mice, we were able to look at a set of human patients and predict outcomes correctly 75 percent of the time.”
Like so many mysteries around COVID-19, our understanding of why this respiratory infection affects so many other parts of the body is limited by the novelty of the virus itself. The earliest known cases of COVID-19 are still only a few months old at this point, so it will take some time before we can start to untangle how exactly the virus impacts our body.
CORRECTION (May 28, 2020, 1:32 p.m.): Angela Rasmussen’s last name was incorrectly spelled Rassmussen in some instances in a previous version of this story.