Long COVID Is Real and Presents These Conditions — or Does It?

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Loss of smell. Fatigue. Mental health challenges. Difficulty breathing and other lower respiratory diseases. Fluid and electrolyte disorders. Cardiac dysrhythmia and other nonspecific chest pains. Trouble with urination. Diabetes?

Statistically, these are the conditions that defined post-acute SARS-CoV-2 (PASC) infection, or long COVID, for 28,118 people who tested positive for SARS-CoV-2 by PCR before the Omicron wave. The data, presented at the Conference on Retroviruses and Opportunistic Infections 2022, can be used to guide diagnoses of long COVID, and may be the guide soon at Kaiser Permanente offices, said Michael Horberg, MD, executive director of research, community benefit, and Medicaid strategy at the Mid-Atlantic Permanente Research Institute, in an interview with Medscape Medical News.

“There are some real conditions you could ask about” if you were evaluating a patient who believes they have PASC, Horberg said. “And there are real conditions that are symptoms patients have but they don’t fit the PASC diagnosis.”

That list is likely to evolve as specific symptoms emerge with new variants, he said. And there’s also the nationwide Researching COVID to Enhance Recovery (RECOVER) trial being conducted by the National Institutes of Health (NIH). Horberg is withholding judgment on diabetes, though, until more data come in.

During the global pandemic, Horberg, an HIV physician by training, found himself writing policies and guidelines for Kaiser’s Mid-Atlantic States (KPMAS) COVID response. Not long after that, the reports of symptoms that have come to be called long COVID started to come in. But they were “a mishmash of things” — everything from binge eating to the skin condition vitiligo to cranial nerve impairment, along with the more common complaints like fever, insomnia, and shortness of breath.

So Horberg looked back through KPMAS patient charts and found 28,118 members who had received a positive SARS-CoV-2 PCR test result in 2020. Then he matched them 3:1 with 70,293 members who didn’t have a positive PCR. The majority were women, nearly half were younger than 50, more than 40% were Black, and 24.5% were Latinx. The majority met clinical definitions of overweight or obese and many had other chronic illnesses, including diabetes (18.7% in the COVID-positive group), chronic kidney disease (3%) and cancer (2.6%). Rates of chronic illnesses were similar between arms.

Then they went back to 4 years before each positive PCR test and looked for all the illnesses before COVID, all those that emerged within 30 days of COVID diagnosis and those illnesses that emerged between 1 and 3 months after diagnosis.

From that search, they found 15 symptoms that were more common among people who’d had COVID. In addition to the symptoms listed above, those also included abdominal pain, other nervous system disorders, dizziness or vertigo, and nausea and vomiting. Then they looked at whether each patient had experienced those symptoms in the 4 years before COVID to see if they were, in fact, new diagnoses.

More Than 1 in 10

About 1 in 4 people who’d had COVID reported symptoms they thought might be long COVID, but through the analysis, they found that only 13% actually developed new conditions that could be categorized as long COVID.

“When you start controlling for all those chronic conditions, a lot of symptoms fall out,” Horberg told Medscape Medical News. “Plus, when you start comparing to the COVID-negative population, especially in the first 30 days of your positive diagnosis, actually, the COVID-negative patients have essentially almost the same amount, sometimes more.”

For instance, in the first month after diagnosis, though people with COVID reported anxiety symptoms after their diagnoses, people who’d never had COVID were coming in even more often with that symptom. And although gastrointestinal disorders were common in people who’d had COVID, they were just as likely in people who had not. Nausea and vomiting were actually 19% more common in people without COVID as those with it. And people without COVID were nearly twice as likely to develop nutritional and endocrine disorders.

In the longer run, people who’d had COVID were 25% more likely to develop dysrhythmias, 20% more likely to develop diabetes, 60% more likely to develop fatigue, 21% more likely to develop genitourinary conditions, 39% more likely to develop chest pains, and a full 3.88 times more likely to develop trouble with olfaction.

And although people who’d had COVID were numerically 5% more likely to develop both abdominal pain and vertigo, 4% more likely to develop nervous system disorders, and 1% more likely to develop anxiety disorders longer term, none of those reached statistically significance.

The only diagnosis that doesn’t make sense to Horberg is diabetes.

“At this point I don’t think it’s been fully explained,” Horberg told Medscape Medical News. “I don’t think COVID is affecting the pancreas. But I do think that these are people who probably sought medical care, who hadn’t been seeking medical care and that the findings of diabetes were incidental diagnoses.”

Still, Horberg isn’t saying never on that. “As they say, more research is needed,” he added.

Ready to Define Long COVID?

As an intensive care unit physician and pulmonologist, Michael Risbano, MD, assistant professor of medicine at the University of Pittsburgh School of Medicine, has seen a lot of COVID. As the co-manager of the medical system’s post-COVID clinic, he’s also seen a lot of people coming in for help with what could be long COVID. When he saw the data from Horberg’s presentation, at first it seemed to confirm what he’d already known. But then he looked further.

“Well, this is actually making sense,” Risbano thought. At his clinic, it’s been an ongoing challenge to tease out what symptoms existed before COVID. Unlike Kaiser, the University of Pittsburgh Medical Center is not a closed system.

“We know some people who tend to get sick [with COVID] have some underlying medical issues already,” Risbano told Medscape Medical News. “But we don’t always have a good baseline as to what they were like beforehand, so we don’t always know what’s changed.”

He said the study design here, though retrospective and based on chart review rather than prospective observation, starts to put symptoms into the larger context of a patient’s life. And the diabetes association really stood out to him. He recalled one patient who, when she was admitted to the ICU, had a hemoglobin A1c that was totally normal. But when that patient returned a few months later, her blood sugar had skyrocketed.

“It was sky-high, like 13, and she was in diabetic ketoacidosis,” he said. “I know that’s an N of 1, but my wife is a dietitian and a case manager, and she’s having a lot of people coming in with a new diagnosis of diabetes.”

Still, he said he’s not sure that the conditions the study identified should be the basis for a definition of long COVID.

“I don’t know if you can come up with a definition out of this,” he said. “But I think this is at least helpful in telling us what disease states are different pre- and post-COVID, and what sorts of diagnoses clinicians should look for when a patient comes in after having a COVID diagnosis.”

Horberg and Risbano have disclosed no relevant financial relationships. The study was funded by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Conference on Retroviruses and Opportunistic Infections 2022: Abstract 98. Presented February 15, 2022.

Heather Boerner is an infectious disease and disparities reporter based in Pittsburgh, PA. Her book, Positively Negative: Love, Pregnancy, and Science’s Surprising Victory Over HIV, came out in 2014.

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