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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?

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“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.  

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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.  

Her clinic evaluates patients and offers advice and sometimes medications, to manage dizziness caused by low blood pressure, for example. Sometimes Lypson refers patients to cardiologists, aware some may be at risk for future cardiovascular complications, or to neurologists, who can evaluate numbness or tingling as well as cognitive symptoms. She’ll recommend a memory clinic to patients who she thinks can be helped by specialists typically treating people with dementia or delirium.

A few patients have told Lypson their problems finally began to dissipate five or six months after they fell ill with Covid-19. It’s not enough to pronounce them cured or to predict another patient’s trajectory, but it does give her hope. In the meantime, she makes sure patients see a physical therapist to help them manage activities of daily living — for example, dressing, showering, eating. “We use physical therapy as a tool to help us understand what accommodation might be needed,” she said.

Some patients have come to the GW clinic rather than remain on a waiting list for the Mount Sinai Center for Post-Covid Care in New York. When it opened in May, it was among the first to devote its attention to long haulers and study their post-infection course. More than a thousand patients have been evaluated, said Zijian Chen, the center’s medical director, but treating them is still like traveling in unexplored territory.

“There’s really no Covid-19 experience. This is a completely new disease,” he said. “A lot of it is almost trial and error in that we look for things that may help with the symptoms, that we try to see if it works on certain patients.”

Patients are screened for inflammatory markers in their blood or for memory problems. Imaging is performed to spot structural damage to the lungs, heart, or other organs. And symptoms are addressed: They learn breathing exercises or how to build up exercise tolerance. Some people do feel better.

“Not everybody is getting back to normal,” he said. “But there is some good response to some of the things that the groups are doing.” 

He hopes treating and studying these patients will lead to improved outcomes, just as the recognition of unusual blood clots and who benefitted from ventilators did earlier in the pandemic. 

At outpatient clinics run by Spaulding Rehabilitation Hospital in Boston, patients are also offered strategies to cope with symptoms. That might be developing compensatory skills for memory problems, assessing joint complaints and their causes, or building muscle through controlled exercise, said Ross Zafonte, chief medical officer. Other medical problems are evaluated, whether they are cardiac, pulmonary, or related to peripheral nerve disease.

Patients are also invited to participate in research to unravel the reasons why the virus can have such lasting effects, but the primary message Zafonte wants to send is that care is available. “There are a lot of people with symptoms,” he said. “There are opportunities [for people] to be seen in clinics that focus on this.” 

Lypson, Zafonte, and Chen all worry about the psychological impact on patients.

“The world is a gloomy place, unfortunately, right now,” Chen said. “It’s even worse for them. They have to deal with all these extra symptoms so their anxiety, their level of sadness, their depression is higher. I want patients to know that this is normal and that there’s help out there.”

  • Dr.s will need time to really be able to help the longhaulers who are suffering the side effects of Covid 19. My heart goes out to them and they are in my prayers.

  • I’ve been telling doctors about long haul symptoms since getting sick on February 24. I typically use the VA but I was too sick to drive that far so I went to my previous private doctor. He walked into the exam room and immediately said I had seasonal allergies and sent me on my way. No tests other than swabbing my nose to check for the flu.

    It’s been 10 months and I still have multiple Covid symptoms. According to the VA doctors it’s all related to my age even though ALL my symptoms started on Feb. 24th. No one believes I had the virus since I wasn’t tested initially. Very frustrating. I’ve lost faith in all doctors and now I’m just coping with my symptoms day by day. I don’t even talk to my friends and family about it any more. They just don’t care.

    Good luck to all long haulers. Your going to need it!

  • Hopefully a new & revamped CDC and other health institutions will be smart enough to fund R&D for this syndrome that likely millions of Americans will be saddled with as numbers keep rising. Obviously such funding is a worthwhile investment to prevent billions in health care costs for the long haul illnesses that ought to be recognized as such. Maybe when the medical system is no longer buckling under the load of accute Covid cases there will be more attention paid to this clearly real after effect.

  • Why does UCSF keep advertising that they have a post covid clinic? My 1 year old daughter and I have been extremely sick with long covid since the end of February and no one will allow us to participate in the studies or give us rehabilitation at the clinic. They won’t even give me the diagnosis or post covid syndrome even though i have suffered every COVID specific symptom, including loss of smell and taste, covid toes, viral pink eye, memory loss, vision loss, pneumonia, and my hair is profusely falling out. My daughter has intermittent rashes, ongoing low grade fevers, is displaying severe neurological symptoms, and is developmentally delayed due to this horrible chronic viral infection. I have advocated for myself for 10 months despite being severely ill and have not found one doctor at UCSF who will believe me. This is criminal to let hundreds of long covid patients suffer at home with no guidance, no diagnosis, and no options for treatment. We are STILL showing evidence of viral symptoms, the same as day one. Give us at least the option of a clinical trial with antivirals. PLEASE

  • My wife was diagnosed with ground glass and inflammation of her lungs. She suffers from fatigue, some cognitive issues, restless sleep, trouble swallowing at times, ringing in her ear, constipation, muscle weakness, shortness of breath..these symptoms had started in March and has progressively gotten worse. We have been besides to her primary physician..to a Hematologists, Gastro dr, Cardiologist, and now a Neurologist and so far no diagnosis. The health care system pushes us away. Rest and see you in two to four months. We want answers and there seems to be none

  • Excelent aproach to start tracing this symptoms after the acute face we are seeing this happen in patients after their recovery or asymptomatic

  • Funny how this sounds exactly like what we in the Lyme disease world go through & the CDC doesn’t believe us. Symptoms similar and Lyme also hides with a biofilm protection to only come back later. And makes you wonder – both diseases made in a lab? Wuhan & Plum Island? Wish someone would ask all these scientists about that.

  • I am a Pediatric RN that got Covid November 13th.I am still experiencing symptoms that will not go away such as dizziness extreme fatigue, brain fog sense of smell and taste coming back slowly. I am frustrated by this. Are there any studies near the Pgh.PA area that I can participate in

  • The following article is an interesting read about the SAR-COV2 hiding in inaccessible tissue.

    https://www.reuters.com/article/uk-health-coronavirus-science/uk-variant-linked-to-high-viral-loads-neanderthal-gene-offers-protection-idUSKBN2921Z7

    This coronavirus does not behave like a respiratory disease. It hid in the eyes and in the made reproductive organs. The HIV does the same. This virus also has the same gene mutation as the HIV and ebola allowing it to bind to the cell more easily.

    Question, is it possible for this covid hid in other part of the body and stay dormant to come back later on?

  • Why does this article never once mention Mylagic Encephomilitis aka Chronic Fatigue Syndrome? The debilitating post-viral illness that has stumped doctors and scientists for decades and left patients disbelieved and dismissed?

    • If the medical establishment had spent less time denying or downplaying ME/CFS and more time researching it, we might have a treatment approach ready to go. Now they’re being forced to deal with the COVID reality.

      My daughter has taken 5 years to mostly recover from a similar post-viral syndrome that resulted in idiopathic hypersomnia, POTS, brain fog, and other autonomic dysfunction. If my wife and I hadn’t both been scientists, it would have taken much longer to get her diagnosed and treated (not that the treatments were great, just addressing the symptoms). Post-COVID patients shouldn’t assume this is going to go away in months.

    • Looks like we’ll be getting collateral knowledge about ME/CFS in the near future.

      Another hope is that 21st century doctors will quit dismissing syndromes and symptoms they don’t understand and just admit they’re clueless. As we see here, that opens up the next step: helping their patients manage. Long-covid patients will also need legal disability protection.

      In the meantime, my own relatively mild ME/CFS symptoms are one of the reasons I’ve been very conservative about protecting myself during this pandemic.

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