Without Guidelines, Docs Make Their Own Long COVID Protocols

Nov. 22, 2022 – Diagnosing long COVID is something of an art for doctors who, without any formal criteria, say they know it when they see it. Treating the condition requires equal combinations of skill, experience, and intuition, and doctors waiting for guidelines have started cobbling together treatment plans designed to ease the worst symptoms.

Their work is urgent. In the U.S. alone, as many as 29 million people have long COVID, according to estimates from the American Academy of Physical Medicine and Rehabilitation.

“Patients with long COVID have on average at least 14 different symptoms involving nine or more different organ systems, so a holistic approach to treatment is essential,” says Janna Friedly, MD, executive director of the Post-COVID Rehabilitation and Recovery Clinic at the University of Washington in Seattle. 

For acute COVID cases, the National Institutes of Health has treatment guidelines that are taking a lot of the guesswork out of managing patients’ complex mix of symptoms. This has made it easier for primary care providers to manage people with milder cases and for specialists to come up with effective treatment plans for those with severe illness. But no such guidelines exist for long COVID, and this is making it harder for many doctors – particularly in primary care – to determine the best treatment. 

While there isn’t a single treatment that is effective for all long COVID symptoms – and nothing is approved by the FDA specifically for this syndrome – doctors do have tools, Friedly says. 

“We always start with the basics – making sure we help patients get enough restorative sleep, optimizing their nutrition, ensuring proper hydration, reducing stress, breathing exercises, and restorative exercise – because all of these are critically important to helping people’s immune system stay as healthy as possible,” she says. “In addition, we help people manage the anxiety and depression that may be exacerbating their symptoms.”

Fatigue is an obvious target. Widely available screening tools, including assessments that have been used in cancer patients and people with chronic fatigue syndrome, can pinpoint how bad symptoms are in long COVID patients. 

“Fatigue is generally the number one symptom,” says Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the COVID-19 Recovery Clinic at the University of Texas Health Science Center in San Antonio. “If a patient has this, then their therapy program has to look very different, because they actually do better with pacing themselves.”

This was the first symptom tackled in a series of long COVID treatment guidelines issued by the medical society representing many of the providers on the front lines with these patients every day – the American Academy of Physical Medicine and Rehabilitation. These fatigue guidelines stress the importance of rest, energy conservation, and proper hydration. 

For patients with only mild fatigue who can still keep up with essential activities like work and school, activity programs may begin with a gradual return to daily routines such as housework or going out with friends. As long as they have no setbacks, patients can also start with light aerobic exercise and make it more intense and frequent over time. If symptoms do not worsen, they can ramp up exercise by about 10% every 10 days. 

But with severe fatigue, this is too much, too soon. Activity plans are more apt to start with only light stretching and progress to light muscle strengthening before any aerobic exercise enters the picture. 

“Traditional exercise programs may be harmful to some patients with long COVID,” says Verduzco-Gutierrez. “Many cannot tolerate graded exercise [where exertion slowly ramps up], and it actually can make them worse.” 

There’s less consensus on other options for treating fatigue, like prescription medications, dietary supplements, and acupuncture. Some doctors have tried prescription drugs like the antiviral and movement disorder medication amantadine, the narcolepsy drug modafinil, and the stimulant methylphenidate, which have been studied for managing fatigue in patients with other conditions like cancer, multiple sclerosis, traumatic brain injuries, and Parkinson’s disease. But there isn’t yet clear evidence from clinical trials about how well these options work for long COVID. 

Similarly, interventions to tackle neurological symptoms and cognitive problems borrow a page from treatments used for other conditions like stroke and dementia – but require changes to meet the needs of those with long COVID. Four in five long COVID patients with neurological and cognitive issues have brain fog, while more than two-thirds have headaches, and more than half have numbness and tingling in their extremities, loss of taste, loss of smell, and muscle pain, one study suggests.

Patients with deficits in areas like memory, attention, executive function, and visual and spatial planning may get speech therapy or occupational therapy, for example – both approaches that are common in people with cognitive decline caused by other medical conditions. 

Doctors also promote good sleep practices and treating any mood disorders – both of which can contribute to cognitive problems. But they often have to skip one of the best interventions for improving brain function – exercise – because so many long COVID patients struggle with fatigue and exertion or have cardiovascular issues that limit their exercise. 

The lack of formal guidelines is especially a problem because there aren’t nearly enough specialists to manage the surge of patients who need treatment for issues like fatigue and brain fog. And without guidelines, primary care providers lack a reliable road map to guide referrals that many patients may need. 

“Given the complexity of long COVID and the wide range of symptoms and medical issues associated with long COVID, most physicians, regardless of specialty, will need to evaluate and treat long COVID symptoms,” says Friedly. “And yet, most do not have the knowledge or experience to effectively manage long COVID symptoms, so having guidelines that can be updated as more research is conducted is critical.”

One barrier to developing guidelines for long COVID is the lack of research into the biological causes of fatigue and autonomic dysfunction – nervous system damage that can impact critical things like blood pressure, digestion, and body temperature – that affect so many long COVID patients, says Alba Miranda Azola, MD, an assistant professor and co-director of the Post-Acute COVID-19 Team at Johns Hopkins University School of Medicine in Baltimore. 

Research is also progressing much more slowly for long COVID than it did for those hospitalized with severe acute infections. The logistics of running rigorous studies to prove which treatments work best for specific symptoms – information needed to create definitive treatment guidelines – are much more complicated for people with long COVID who live at home and may be too exhausted or too preoccupied with their daily lives to take part in research. 

The vast number of symptoms, surfacing in different ways for each patient, also make it hard to isolate specific ways to manage specific long COVID symptoms. Even when two patients have fatigue and brain fog, they may still need different treatments based on the complex mix of other symptoms they have. 

“All long COVID patients are not equal, and it is critical that research focuses on establishing specific descriptions of the disease,” Azola says. 

The National Institutes of Health is working on this through its long COVID Recover InitiativeIt’s unclear how long it will take for this research to yield enough definitive information to inform long COVID treatment guidelines similar to what the agency produced for acute coronavirus infections, and it didn’t respond to questions about the timeline. 

But over the next few months, the National Institutes of Health expects to begin several clinical trials focused on some of the symptoms that doctors are seeing most often in their clinics, like fatigue, brain fog, exercise intolerance, sleep disturbances, and changes in the nervous system’s ability to regulate key functions like heart rate and body temperature. 

One trial starting in January will examine whether the COVID-19 drug Paxlovid can help. A recent Department of Veterans Affairs study showed patients treated with Paxlovid were less likely to get long COVID in the first place.

Some professionals aren’t waiting for the agency. The Long Covid Research Consortium links researchers from Harvard and Stanford universities; the University of California, San Francisco; the J. Craig Venter Institute; Johns Hopkins University; the University of Pennsylvania; Mount Sinai; Cardiff; and Yale who are studying, for instance, whether tiny blood clots contribute to long COVID and whether drugs can reduce or eliminate them.

“Given the widespread and diverse impact the virus has on the human body, it is unlikely that there will be one cure, one treatment,” says Gary H. Gibbons, MD, director of the National Heart, Lung, and Blood Institute at the National Institutes of Health. “This is why there will be multiple clinical trials over the coming months that study a range of symptoms, underlying causes, risk factors, outcomes, and potential strategies for treatment and prevention, in people of all races, ethnicities, genders, and ages.