For Some Patients, Long Covid Symptoms Mask Something Else

It was overuse of acetaminophen that finally led to Nic Petermann’s cancer diagnosis. For months, the then 26-year-old had been contending with exhaustion, night sweats, recurring fevers, and abdominal pain so debilitating that she regularly woke up in the middle of the night to take soothing baths. Her persistent flu-like symptoms, she’d read online, were probably just the lingering effects of a Covid infection she’d had in January 2021; the pain was the odd symptom out, but an ultrasound had turned up nothing.

Come June, the pain was too much to bear—Petermann called a telehealth hotline and was immediately referred to the hospital after the staff heard how much acetaminophen she had been taking. After extensive testing, Petermann finally had an answer: All her symptoms, including those that seemed to be long Covid, were due to Stage IV Hodgkin’s lymphoma. She started chemotherapy the next day.

Today, Petermann is in remission, though she still deals with the long-term consequences of the aggressive, monthslong chemo. If she hadn’t assumed most of her symptoms were due to long Covid, she says, she may have received proper treatment and a diagnosis much earlier. “When I went to get my pain symptoms checked out, I didn’t mention the flu-like symptoms, because I just thought that was something that I would have to deal with,” she says.

Most people with Petermann’s symptoms won’t end up in her position. Long Covid is common—estimates of its prevalence vary widely , but even the most conservative studies imply that millions of people are dealing with long-lasting symptoms of their infections. Hodgkin’s lymphoma, on the other hand, is rare.

But with dozens of possible symptoms , long Covid can be easily confused with countless other conditions, including cardiovascular diseases such as hypertension and diabetes, autoimmune diseases like lupus and multiple sclerosis, and cancer. Add the fact that Covid can make preexisting conditions worse, and determining whether or not someone has long Covid becomes a daunting task. Parsing these vast sets of alternatives has become the responsibility of clinicians on the vanguard of long Covid care, from the primary care physicians whom patients first seek out to the experts who staff long Covid clinics.

For each patient they must perform a careful differential diagnosis, a medical term for the process of considering every possible cause of a patient’s set of symptoms. Accurate differential diagnosis is essential not just for getting patients care, but also for furthering medical understanding of a still-obscure condition. “We need to be cautious not to turn long Covid into a catch-all diagnosis,” says Linda Geng, codirector of the Stanford Post-Acute Covid-19 Syndrome Clinic.

In the absence of any objective tests, however, long Covid remains a “diagnosis of exclusion”—one that is made only after other reasonable possibilities have been exhausted. Recent data suggest that many patients will emerge from this process with a diagnosis not of long Covid, but of something else. A July paper in Nature that analyzed the medical records of over 2 million patients in the UK found that, while 5.

4 percent of those with a previous Covid infection had at least one long Covid symptom recorded in their charts, 4. 5 percent without evidence of infection also had at least one symptom. In other words, long Covid symptoms are meaningfully common in people who have never contracted Covid—so even those who have had the illness might be experiencing persistent symptoms for unrelated reasons, says Shamil Haroon, associate clinical professor of public health at the University of Birmingham and the Nature study’s senior author.

(Haroon notes that these numbers are likely vast underestimates—many doctors only write patient symptoms in the free text portion of patient charts, which the study did not examine. ) Similarly, an August paper published in The Lancet found that 21 percent of recent Covid patients in the Netherlands reported at least one symptom that worsened after their Covid infection, whereas 9 percent with no evidence of infection had similar symptoms. These high-level statistics are borne out by the experiences of long Covid specialists.

By the time someone makes it to their clinics, they’ve usually already been through testing elsewhere—typically with their primary care provider—and the most obvious alternatives have been considered and rejected. And yet many patients leave these clinics with a diagnosis they did not expect. Fernando Carnavali, site coordinator of the Center for Post-Covid Care at Mount Sinai West in New York, described the situation as “not uncommon.

” Nisha Viswanathan, codirector of the UCLA Health Long Covid Program, estimates that a quarter of the patients she sees end up diagnosed with something other than long Covid. This can be a matter of urgency. “You wouldn’t want to miss shortness of breath being caused by a sudden blood clot in the lungs, or chest pain being caused by a heart attack,” says Jason Maley, director of the Beth Israel Deaconess Medical Center Critical Illness and Covid-19 Survivorship Program.

More often, though, differential diagnosis is a long, sometimes discouraging, process that involves interrogating multiple explanations for each symptom. Patients might come in with half a dozen or more distinct complaints. Different clusters of those complaints suggest different potential explanations, creating a combinatorial explosion of diagnostic possibilities.

“The differential diagnosis is immense,” Carnavali says. “That is the challenge. ” That’s not to say it’s impossible.

Doctors at specialty clinics have seen enough long Covid patients that they can identify some characteristic patterns. Michael Brode, medical director of UT Health Austin’s Post-Covid-19 Program, says that almost all of the long Covid patients he has seen start developing their symptoms within six weeks of their infection; if there’s a longer delay, he suspects something else. Symptoms that group together can help point doctors toward what that something else might be.

Most of the long Covid patients Brode sees who exhibit fatigue and the sluggish thinking known as “ brain fog ” are also dealing with post-exertional malaise—extreme exhaustion after physical, mental, or emotional effort. So when a man came into his clinic with the first two symptoms but not the third, Brode suspected that something else might be going on. He eventually discovered that the patient was dealing with a large, benign brain tumor.

A benign brain tumor may not seem like good news. Unlike long Covid, though, it is curable. Clinicians don’t have many tools for alleviating long Covid beyond lifestyle changes and rehabilitation exercises; while these can make an enormous difference, they don’t necessarily offer the same succor as a pill or a surgery.

Even Petermann, who received a cancer diagnosis, described “the relief of actually knowing what it was and knowing there was going to be a treatment. ” Yet a long Covid diagnosis can also be a form of solace—and validation. “People often come to my clinic and are just relieved for me to explain why I think their symptoms fit with what we’ve seen with long Covid,” Maley says.

Going through a diagnostic process based on excluding other problems can be frustrating, with the patients receiving endless “normal” test results despite feeling that something is wrong. “Normal doesn’t mean everything they’re going through is normal,” Brode says he tells his patients. “It just means it’s not something else.

” Patients have come to him describing symptoms so unusual that they expect he won’t believe them—an internal vibrating sensation, for example—and Brode is able to tell them that not only are their symptoms real, but he has seen them in a number of other long Covid patients. Not all patients have access to this kind of expertise. Most US states have only a few long Covid clinics; some have none at all.

Some patients don’t have a primary care doctor; as a result, long Covid clinicians have had to take on the role of filling gaps in the nation’s medical system. (Carnavali recalls one patient whom he diagnosed not with long Covid, but with uncontrolled diabetes so severe that the person needed immediate treatment. ) These clinics, however, were not designed to carry the full weight of chronic illness care in a broken health care system.

“This is all very much indicative of a system that had never anticipated these kinds of care needs,” Viswanathan says. And their care also doesn’t reach patients who, like Petermann, delay testing because they’ve already chalked their symptoms up to long Covid. As doctors see more suspected long Covid cases, they will become increasingly skilled at its differential diagnosis—but patients will have to seek out that expertise.

As a UK resident, Petermann could take advantage of her country’s socialized health care system. Even so, it took many months for her to get her cancer diagnosis. If she could do it all over again, she says, she would have asked doctors about all her symptoms—not just her pain—and asked them to consider other possibilities when scans didn’t turn up anything.

“If you know something’s wrong,” she says, “push for answers. ”.