Five years later, long COVID remains a frustrating medical mystery for thousands of Minnesotans

Thousands of Minnesotans remain exhausted and disabled after their COVID-19 illnesses, but why they got “long COVID” while millions of others who got sick did not remains a mystery.

Maybe COVID-19 reawakened dormant viruses in their bodies. Or enough COVID virus lingered to continue causing havoc. Or COVID caused lasting organ damage before the immune system snuffed it out. Or the immune system went into overdrive in response to the infectious disease.

Dr. Amy Engebretson has wondered why she was so unlucky. A routine COVID illness in March 2020 left her so tired months later that she gave up her OB-GYN practice. Years later, she still sleeps about half of every day while waiting for answers and hoping for better treatments.

“I’m still really nowhere near the person that I was,” the former triathlete and distance runner said.

Long COVID is arguably the most significant hangover from the pandemic, five years after it emerged in Minnesota, affecting everything from the stability of the state’s workforce to the viability of its health systems.

One federal survey in 2023 suggested around 385,000 Minnesota adults endured long COVID, while another last fall estimated the number could be closer to 700,000. Most recovered, but as many as 50,000 have ongoing, significant impairments in their daily lives.

Either estimate reveals a challenge, said Dr. Stephanie Grach, a clinician who specializes in post-COVID cases at Mayo Clinic in Rochester. Her patient population mirrors national estimates, with disproportionate numbers of minorities, middle-age adults and women.

Long COVID hasn’t been diagnosed as often in seniors, surveys show, even though they sustained the majority of COVID hospitalizations and deaths.

Seniors might be dismissing long COVID symptoms as routine aches and pains of aging. But Grach said there are disproportionate cases among teens emerging from adolescence and women reaching menopause, suggesting hormonal changes could elevate risks for long COVID.

Severe COVID increases the risk of developing long COVID, but Grach said many cases emerge from the larger population of Minnesotans who only had mild infections. The Centers for Disease Control and Prevention recommends vaccination to reduce risks, though Mayo research last year found that the shots did not reduce the odds of being diagnosed with long COVID.

Long COVID, as federally defined, includes symptoms that occur immediately after infections, or later after illnesses resolve. The syndrome can come and go, or get progressively worse. A state survey earlier this year showed fatigue is common among Minnesotans with long COVID, along with shortness of breath and brain fog (disrupted memory and focus).

An estimated 5% to 50% of long COVID cases progress to an exhausting form of chronic fatigue syndrome known by the acronym ME/CFS. Patients in their prime find themselves struggling to get through their days and are punished if they try to return to old routines too quickly.

Amid the pandemic, Engebretson rushed back to work at her busy east metro clinic after her own COVID infection. Her fever had receded and her sense of taste and smell returned, but she still felt tired.

Some days after work, she couldn’t move from her sofa to bed, but she dismissed the concern, she said. “I was like, ‘I can still function. This isn’t so bad.‘”

Rushing back caused post-exertional malaise, and working harder, she later learned, only sapped more strength. “Say you have a dollar’s worth of energy a day. If you spend $10 in one day, you’re going to be in trouble. You’re going to be stuck, you know, laying in bed for a week or two.”

Other viral and bacterial infections triggered this level of exhaustion before the pandemic, but cases were rare and attributed to everything from depression to laziness. But COVID caused so many cases that chronic fatigue has gained legitimacy.

After a leave in summer 2021, Engebretson tried once more to return to her medical practice. The effort lasted a couple weeks. She hasn’t worked since.

Research is starting to map out the biological and cellular origins of long COVID, a key step before new drugs can be tested.

Scientists in San Francisco recently reported COVID interferes with fibrinogen, a protein responsible for blood clotting, causing harmful clots that disrupt nerve cells and brain activity. They also found COVID reactivates old viruses such as Epstein-Barr and disrupts healthy bacteria in the gut.

Grach said long COVID is at least partly linked to an overreaction by the immune system, which “doesn’t seem to be shutting off in the way that it’s supposed to” after illness. Treatments that moderate the immune system could help, but the Mayo doctor said a combination of causes are probably at work.

“If it came down to really one specific cause among these options, then we would already know what specific medicine, what specific therapy, was going to be the answer,” she said.

Sioux Falls-based Sanford Health is among more than 20 institutions participating in the federally funded Recover project, which has amassed observational data about thousands of people with long COVID and their treatments. The project has helped to define the demographic groups most at risk for long COVID, but some advocates have criticized it for conducting too much observation and not investing in enough clinical trials of medications.

Recent budget cuts by President Donald Trump’s administration could save taxpayers money but reduce long COVID research, which has advocates concerned. The pace of discovery was too slow before cuts, especially for patients with ME/CFS, who have about a 5% chance of full recovery, said Billy Hanlon, an advocacy director for the Minnesota ME/CFS Alliance.

“We are five years into this health disaster. … Research is not moving fast enough for the millions suffering,” he said.

Treatment now focuses on managing symptoms, such as adjusting medications for patients suffering more asthma flareups as a result of long COVID, said Dr. Tanya Melnik, co-director of M Health Fairview’s post-COVID clinic in Minneapolis.

Treatments include dexamethasone, a steroid that reduces inflammation. Guanfacine treats ADHD but appears to reduce brain fog as well, Melnik said.

She tailors therapy and exercise plans for patients to help them maximize their energy without pushing too far and causing malaise. Disrupted blood flow is a problem in long COVID patients, and exercise can reverse that, she said.

Doctors hoped that the antiviral Paxlovid would help by clearing out lingering virus in patients with long COVID, but studies have been inconclusive. A report from Minnesota’s new Long COVID Guiding Council couldn’t recommend it to doctors.

Clinicians have seen delayed recovery, after months or years of having long COVID, so Engebretson remains hopeful. Her brain fog has lifted to the point that she can read more. Daily meditative breaks help.

She volunteers some of her waking hours, helping to promote research and treatment options through a weekly long COVID newsletter. She encourages people to seek treatment of initial COVID illnesses, because that can reduce the progression to long COVID, and to take symptoms seriously.

“I am a doctor, you know. I have all the advantages, right? But it took me like a year and a half before I was diagnosed with long COVID,” she said. “Part of it was me. I just wanted to ignore it and pretend that it was not a big deal. And there’s a lot of people walking around like that.”