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Long COVID is real – and complex. A major study aims to untangle its causes.

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"CU researchers see RECOVER as a big step along the path to better treatments and understanding of long COVID.

Rarely has a clinical trial’s name better signaled its ultimate aims. But then, a billion-dollar study deserves a first-rate acronym, too.

RECOVER is the name. It stands for Researching COVID to Enhance Recovery. Its focus is on understanding long COVID – a wide swath of maladies whose roots lay in infection with the SARS-CoV-2 virus that swept the planet starting in late 2019 and continues to mutate and spread, if much less aggressively than during the pandemic. Each infection or reinfection opens the door to long COVID (also called post-acute sequelae SARS-CoV-2 infection, or PASC). We may have moved on from COVID, but COVID has not moved on from us.

The number of long-COVID cases is hard to nail down, but it’s big. One review, which considered 194 studies totaling 735,000 participants, found that, “on average, at least 45% of COVID-19 survivors, regardless of hospitalization status, went on to experience at least one unresolved symptom” an average of four months after infection. The U.S. Centers for Disease Control and Prevention says 19% of those who reported having COVID-19 in the past have long-COVID symptoms. Another review estimates that 10% to 30% of non-hospitalized cases, 50% to 70% of hospitalized cases, and 10% to 12% of vaccinated cases end up with long COVID. Considering that as many as 94% of U.S. residents have gotten the coronavirus at some point, these percentages yield millions of people.

The University of Colorado School of Medicine is one of 86 medical centers around the country participating in the four-year, $1.15 billion National Institutes of Health RECOVER study. It has enrolled more than 12,000 people so far. The CU School of Medicine site at UCHealth University of Colorado Hospital on the Anschutz Medical Campus (UCH) has signed up about 240 patients and counting.

Many health conditions under the long COVID umbrella

RECOVER will probably be the largest U.S. trial of its kind, says Dr. Kristine Erlandson, the infectious disease specialist who leads the study’s Colorado site. The study’s size and its inclusion of a control group of those who never had COVID-19 are important, she says. RECOVER’s leaders have also made an effort to enroll populations that have been underrepresented in many previous COVID studies, such as Hispanic/Latino populations and rural residents. While the study is ongoing, Erlandson says it has enormous potential to help future long-COVID patients.

“I think it’s going to be very important to the field,” she said. “I think there will be, eventually, thousands of papers that leverage this RECOVER cohort to really advance our knowledge of long COVID.”

Improving the diagnosis and treatment of long COVID will be important to millions of people. The disease best known for its spread by the lungs can also impact a wide range of bodily systems over time: the immune system, the brain and neurological system, the gastrointestinal tract, the heart and circulatory system, and the reproductive system among them.

A recent, comprehensive review listed a few of the “multiple adverse outcomes” under the long COVID umbrella: cardiovascular, thrombotic (blood clot-related), and cerebrovascular (brain-related) disease, type 2 diabetes, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and dysautonomia (especially postural orthostatic tachycardia syndrome, or POTS). That’s just a small selection of a long list of documented long-COVID symptoms.

Some are easier to treat than others. Some may last for years. Some, such as ME/CFS and dysautonomia, which renders up to 75% of those with the severe form of the disease unable to work, “are expected to be lifelong,” as the authors put it.

Long COVID broke into five maladies

Critical-care medicine specialist Dr. Sarah Jolley, medical director of the UCHealth Post-COVID Clinic, is co-author of a forthcoming RECOVER-based study that assigns many of the long COVID-related maladies into five domains, she says. They include:

  • ME/CFS including post-exertional malaise (PEM).
  • Dysautonomia and POTS.
  • Neurocognitive symptoms (such as “brain fog”).
  • Cardiopulmonary exercise intolerance.
  • Persistent olfactory (related to the ability to smell) problems.

Jolley has seen them all. She has consulted with about 1,200 patients since the UCHealth Post-COVID Clinic launched in 2020.

“A lot of those same symptoms that were described early on have been solidified into discrete syndromes that come under the umbrella of long COVID,” Jolley said."

More in the University of Colorado Health article here:


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