What Should We Expect From Long COVID Treatment?

This story is part of a series where we look at the ways COVID-19 has changed our lives and how it will continue to affect public health in 2022.

In 2021, over 34 million people contracted COVID-19 in the United States. Of those people, studies estimate that as many as half will develop long COVID: a complex, multi-systemic illness that follows the initial infection. For some, this may manifest as a lingering cough or the permanent loss of taste and smell. For many, it morphs into a severe disability, with an endless litany of symptoms.

In 2021, these patients finally received an official, medical name for their illness: post-acute sequelae of SARS-CoV-2 infection (PASC). 

Unfortunately, for many patients, that was as far as they got. Two years into the pandemic, long COVID still raises more questions than it offers answers. We took a look at some of what 2021 managed to unravel about long COVID, and what patients hope 2022 will hold.

Progress Made in 2021

In July, the Patient-Led Research Collaborative (PLRC), a team of long COVID patient-researchers, published the first study capturing the full spectrum of long COVID’s 200-plus symptoms, showing how it can impact every organ, and emphasizing that it can occur in non-hospitalized, mild, or asymptomatic cases.

“Personally, this was a big milestone,” Hannah Wei, a long-hauler, qualitative researcher, and co-leader of PLRC, told Verywell. “We originally published this preprint on Medrxiv about a year ago and received both support and pushback from the academic world, then we were faced with several months of rejections by journals and revisions.”

That same month, President Joe Biden announced that long COVID could qualify as a disability, and patients could file for coverage under the Americans with Disabilities Act.

Mechanisms Behind COVID

Studies throughout the year also painted a clearer picture of the mechanisms behind long COVID, underpinning the neurological, vascular, autoimmune, and inflammatory components of the illness. Some symptoms were pinned down to a particular cause, though the full clinical picture still has many gaps.

For example, in 2020, terms like “brain fog” were used by long-haulers to describe cognitive symptoms such as memory loss and trouble concentrating. In 2021, we found out what was behind those symptoms: brain damage, neuroinflammation at the cellular level, seizures, strokes, and even particles of the virus trapped in their brains.

In 2020, the most pervading symptom documented by long-haulers was fatigue. In 2021, a study by the World Health Organization (WHO) showed that Epstein-Barr Virus (EBV), the virus behind mononucleosis, was reactivating in long-haulers, and could be a source of that fatigue.

And that fatigue—according to Lauren Nichols, who has been living with long COVID and reactivated EBV for almost two years—is more than mere tiredness.

“Doctors need to understand that when we say chronic fatigue, we’re saying our bodies are hurting to simply move and to be alive and to function,” Nichols, who is also the Body Politic vice president, told Verywell. “This is a known symptom of chronic EBV, and I think stressing that is important because it helps people to understand that when EBV does reactivate, the fatigue feels different and is debilitating.”

Many studies last year showed that long COVID can present as a post-viral conglomeration of different illnesses, specifically myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), mast cell activation syndrome (MCAS), and dysautonomia, which refers to a dysfunction in the autonomic nervous system. These illnesses can trigger symptoms across every organ system.

Experts emphasize that PASC could be an umbrella term that includes these illnesses, amongst other things.

ME/CFS, for example, shares three of the most common symptoms as long COVID: brain fog, fatigue, and post-exertional malaise (PEM), which is when a patient’s symptoms worsen after activity. Studies have shown this could be triggered by disruption at the cellular level, specifically in our NK T cells, which are usually responsible for fighting off viruses. In ME/CFS, and potentially in long COVID, these cells become impaired, allowing for viral persistence and chronic inflammation. Other studies show that there may be impairment in the part of the cell responsible for producing energy: the mitochondria.

Last year, our understanding of the vascular nature of COVID also expanded. We know it can sear through and damage our blood vessels, use them to travel to any organ, and cause persistent microclots, pulmonary embolisms, heart inflammation, and heart attacks—even weeks after “recovery.” The shifting narrative pointing to COVID as a vascular disease is something that activists like Nichols are emphasizing, especially in mild cases of COVID, as it could be a reason why patients retain long-term damage after recovery.

In December, a preprint study by researchers from the National Institutes of Health (NIH) showed that COVID can linger in the brain, gut, and other organs for more than seven months after the initial infection. This is one of the most exhaustive analyses of the virus’s ability to persist in the body, showing how it can replicate in cells outside of the respiratory tract.

The hope is that these observations and discoveries can help create a broader clinical picture of PASC and provide symptom relief and treatments for long-haulers in 2022.

Are Long Covid Clinics and Treatments Helping?

According to Noah Greenspan, PT, DPT, a cardiopulmonary physical therapist and founder of the Pulmonary Wellness COVID Rehab & Recovery Clinic, one of the most difficult parts of treating long COVID is that the illness can vary from person to person, month to month, and even minute to minute. This, coupled with everything we do not yet know about it, makes it different to create one standard treatment protocol, especially in an outpatient setting.

“What works for some patients may not work and may even be detrimental or harmful to others,” he told Verywell. “This further reinforces the need for close monitoring of signs and symptoms including heart rate and rhythm, blood pressure, and oxygen saturation.”

While many long COVID clinics opened in 2021 to try to treat long-haulers, there are many barriers that prevent patients from accessing them or finding relief.

“Many clinics simply will not accept a patient without a positive test when they had their acute infection with COVID,” Greenspan said. “This is a joke because if we look at who the long-haulers are, a huge percentage of them are young people, mostly women who got sick in early 2020 when one, tests were unavailable and two, people were being told to shelter at home. Many people who probably should have been hospitalized or at least evaluated and treated were turned away.”

Alexis Misko, 34, who had to leave her job as an occupational therapist because of her ongoing long COVID symptoms, told Verywell that traditional methods of rehabilitation are often highly inappropriate with long COVID.

“There is a big lack of understanding of how serious, disabling, and debilitating this illness can be,” she said. “For some, long COVID clinics are not even accessible because people are homebound or bedbound and even visiting a long COVID clinic would cause a severe relapse. … Additionally, it is not clear what the follow-up procedures are with long COVID clinics, meaning that they might discharge someone as ‘recovered,’ never knowing that that person later relapsed.”

Doing too much too fast in treatment or rehabilitation can even lead to worsening symptoms, making long COVID care a delicate balance.

"Many patients seem fine during activity but can then experience debilitating Post-Exertional Malaise (PEM) or Post-Exertional Symptom Exacerbation (PESE)," Greenspan said. "By treating every patient as an individual, erring on the side of caution, pacing and resting as needed, and increasing activity gradually over time as tolerated, we have the best opportunity of first, not harming the patient and second, helping them reach their full potential while avoiding pitfalls like overdoing."

Regarding medications, most of the clinical research examining potential treatments for long-haulers involves the repurposing of old drugs that were developed for other diseases, Susan Levine, MD, an immunologist specializing in ME/CFS and long COVID, told Verywell.

Trials involving intravenous immunoglobulin infusions (IVIG), which have shown to help in ME/CFS, autoimmune dysautonomia, and autoimmune small fiber neuropathy (which many long-haulers are diagnosed with) are also being conducted.

For example, medications used for symptom management of postural orthostatic tachycardia syndrome (POTS), such as beta-blockers, are being prescribed to long-haulers who meet the criteria. Many long-haulers with reactivated latent viruses are finding relief from herpesvirus antivirals. Most medications being used are all for symptom management, but for the long-haulers whose lives have been completely derailed by this virus, it is a start.

But there is still plenty of progress to be made. Many patients have yet to find relief from existing treatments.

What Will 2022 Bring?

In September, the NIH awarded $470 million to the RECOVER Initiative, which aims to study the sources of long-term COVID-19 symptoms and look for possible treatment regimens. Over $1 billion has been spent in researching potential treatment, and more studies will publish their results in 2022.

Throughout the next year, we will be seeing more insight into the pathophysiology of COVID-19. Microbiologists like Amy Proal, PhD, a microbiologist at the PolyBio Research Foundation, and Eric Topol, MD, the founder and director of the Scripps Research Translational Institute, have made many strides in advancing our knowledge of long COVID, and are important scientists to follow both in the clinical sphere and online for updates.

Some long COVID patients hope to see more collaboration in the new year within the medical community.

“Through my challenges with long COVID, I’ve come to the conclusion that teamwork within the medical community is lacking,” Yaron Fishman, 42, who has experienced a variety of long COVID symptoms since November of 2020, told Verywell. “I remember lying on the hospital bed and thinking that if my doctors were able to share what we learned with other hospitals, it could make a big difference.”

Wei also emphasizes that collaborative efforts are needed.

“The challenge ahead is not only for long COVID and disabled patients to be invited to a seat at the table in decision-making,” Wei said. “We are grateful for these opportunities to collaborate with research institutions and public health bodies—but also for the patient voice to be treated as an equal vote. In December PLRC wrote an open letter to the NIH RECOVER stakeholders detailing changes we would like to see in leadership. We advocate for patient engagement to be more transparent, accountable, and meaningful toward the people most affected by these decisions.”

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

Correction - January 20, 2022: This article was updated to reflect a correction in the month Yaron Fishman began to experience long COVID symptoms.