Nearly a year into the coronavirus pandemic, the perplexing problems of Covid-19 long-haulers seem no nearer resolution — or even explanation — than when they first puzzled doctors and patients in the spring.
This much is known: Long haulers, recovering patients whose symptoms persist after their coronavirus infections disappear, are a mix of younger people who never needed hospital care and older people with chronic conditions that predate Covid. Their symptoms trail the infection’s path through their lungs, hearts, muscles, nerves, and brains. Deadening fatigue can dog them for weeks or months. Sometimes their problems wane, then resurface in a stuttering pattern that leaves them wondering if they’ll ever get over the malaise.
With a growing sense of urgency as cases mount across the U.S., physicians have launched specialized clinics to treat and study these “long Covid” patients, creating registries to track their progress. But answers are elusive: Why does brain fog or muscle weakness or shortness of breath linger in some people and not others? What can help lift the fog or restore their vigor? Can these people ever resume normal life?
“I don’t think this is going to be easy to figure out,” said Steven Deeks, a professor of medicine at the University of California, San Francisco, who is leading a clinical trial to find answers. “The vaccines and therapeutics, they were easy. With this post-acute Covid syndrome, we have no idea how to measure it. We have no prior experience in terms of defining it or treating it, so it’s kind of a wild, wild West right now.”
The Centers for Disease Control and Prevention estimates that about a third of Covid-19 patients still feel after-effects two to three weeks after their infections clear and they test negative for the virus. One in four of those people was 18 to 34 years old and had no chronic medical conditions before falling ill with Covid-19, according to CDC’s report, released in July. A survey conducted in the U.K. concluded in November that 1 in 5 people who tested positive for SARS-CoV-2 (the virus that causes Covid-19) suffered from symptoms lasting five weeks or longer; 1 in 10 said their problems lasted 12 weeks or longer.
So far, there is little science beyond case reports and anecdotes to guide clinicians treating these patients, whose difficulties are distinct from the delirium and PTSD sometimes seen after a stay in a hospital intensive care unit. The clinical trial Deeks leads at UCSF is tracking a cohort of people with enduring post-Covid symptoms — some who did and some who didn’t become critically ill from the coronavirus — to build a bank of blood and saliva samples obtained early in their disease to understand virologic, immunologic, and host factors that might correlate with being a Covid-19 long-hauler.
There is a consensus that the problem is more common in women than men, unlike the overall mortality rate, which is higher in men. The CDC survey did not find an association between race and return to full health after Covid-19, but the small number of respondents limits any conclusions to be drawn. How the problems play out in different people is unpredictable, doctors say, with some gradually getting better and others not. Multiple organs are involved, so multiple biological mechanisms might be at play.
Post-viral infection is not new. It’s been seen with Ebola, and the first SARS virus in the early 2000s also gave rise to long-lasting symptoms after some people recovered. A 2009 study in Hong Kong found that psychiatric problems and chronic fatigue still plagued SARS-1 survivors up to four years later. People who completely recover from an Ebola infection can still suffer from fatigue, headaches, muscle, joint and stomach pain, eye problems, memory and hearing loss, and mental health issues. The Ebola virus can persist in their bodies, including in the eyes and the central nervous system, even after being cleared from the rest of the body.
Some theories suggest that prolonged symptoms arise when a patient’s immune system never resets from high alert during the original infection, turning into an autoimmune response that attacks the body, or developing autoantibodies that target shreds of cells destroyed by the virus. The symptoms that Covid-19 long-haulers report resemble those experienced by people with chronic fatigue syndrome/myalgic encephalomyelitis syndrome, believed to be another post-viral infection.
Whether any of this also happens in Covid-19 is unclear. The UCSF study is looking at the “black box of inflammation,” Deeks said. It could be the coronavirus is still causing symptoms, or it’s the ongoing inflammation that’s to blame. Abnormal clotting early in the disease — a hallmark of Covid-19 — could also have damaged the lungs, the heart, and the nervous system.
How long these ill effects last is an open question.
“It’s impossible to study the long-term outcomes of a virus that’s only been around for several months,” Deeks said. “So we are learning as we go.”
While research goes on at UCSF and elsewhere, published reports, anecdotes, and experience are guiding clinicians day to day. As their observations add up, they are accumulating strategies to guide the care they offer patients, which begins with listening to them.
“Meeting patients where they are at and believing them is the most important thing we do, telling them ‘I hear you, I believe you, and I’m going to try to help you navigate the health care system and figure this out,’” said Dr. Monica Lypson, co-director of the COVID-19 Recovery Clinic at George Washington University Medical Faculty Associates in Washington, D.C.
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