Researchers are taking a closer look at long-term COVID. But the treatments may still be an ineffective way

Two years after the COVID-19 pandemic, Question about Long COVID still outnumber the answers. Why do some people develop persistent symptoms — often after a mild case of COVID-19, sometimes even after being vaccinated—While others fully recovered from their brush with the SARS-CoV-2 virus? Why Long COVID seems appear disproportionately in women? How can a condition affect many body systems, causing symptoms ranging from brain fog to joint pain to exhaustion? Is long COVID a single diagnosis, or is it better understood as an umbrella term for a disease, caused by a variety of biologically diverse effects of the virus? Or, it could actually be a new expression of post-viral disease has existed for decades?
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A series of recent studies, some of which have been reviewed and published, and others are currently going through that process, seek to explain why millions of people have persistent COVID. Each contributes a small piece to the larger research puzzle, helping to build a scientific understanding of the disease, bit by bit.

Even so, even if they do, the number of people living with Long COVID increases every day, and there are still very few research-backed treatments to offer them. “The patient is pushing for an answer. Christina Martin, a nurse who runs the Dartmouth-Hitchcock Medical Center Post-Acute COVID Syndrome Clinic in New Hampshire. “They’re looking for the Holy Grail, and it’s not out there.”

What causes long-term COVID

Dozens of lengthy COVID studies have been published in recent months, many of which can be classified into two groups. One team explored what abnormalities in the body caused Long COVID symptoms, while the other sought to identify which individuals are most at risk of developing the condition.

Most recentpublished year nature on March 7, showed that SARS-CoV-2, the virus that causes COVID-19, can damage the brain — even in people who have experienced mild cases. This, the authors write, can lead to long-term problems including cognitive decline, loss of smelland inflammation of the nervous system.

In a similar vein, research to be presented at the European Congress of Clinical Microbiology and Infectious Diseases in April suggests that damage to the vagus nerve – which extends from the brain down to the trunk – is the cause. cause more persistent COVID symptoms. After studying nearly 350 patients with Long COVID, researchers found that 66% had symptoms suggesting vagus nerve damage, including irregular heartbeats, dizziness, and problems with breathing. gastrointestinal. Another recent studypublished March 1 in the magazine Neurology: Neuroimmunology and Neuroinflammationalso points to nerve damage as a possible culprit for many of the symptoms.

But for a complicated condition like long COVID, ie related to more than 200 different symptomsDr Gemma Lladós, an infectious disease doctor at Germans Trias i Pujol Hospital in Spain and one of the researchers behind the study on the vagus nerve, says there won’t be a single cause. Nerve damage could explain many, but almost certainly not all, she said.

The vascular system is another area attracted attention from researchers. Research published year Journal of Biochemistry in February argued that tiny “microclots” in the blood could cause many long-term COVID symptoms by preventing oxygen from reaching the body’s tissues. Similarly, a paper published in a magazine Chest in January showed that a sign of long-term COVID, intolerance to exercise, may be related to poor oxygen delivery.

Other researchers hypothesized that remnants of the SARS-CoV-2 virus can linger in the body, potentially causing long-lasting symptoms. It’s also possible that, for some people, COVID-19 pushes the immune system into hyperactivity, essentially causing it to attack on its own.

That hypothesis is associated with a piece of paper published in a magazine Cabinet in January, this tried to explain why some people develop Long COVID and others do not. Researchers have found four main risk factors associated with developing long-term COVID:

  • Diagnosing type 2 diabetes
  • genetic material from the SARS-CoV-2 virus in the blood
  • evidence of Epstein-Barr virus in the blood
  • the presence of autoantibodies—Moleculars attack the body’s own tissues, rather than foreign pathogens like viruses

Co-author James Heath, president of the Seattle Institute of Systems Biology, said the autoantibody detection was most important, in part because it showed a possible similarity between long-term COVID and autoimmune lupus. While there’s no cure for lupus, “there are treatments available that can work,” says Heath. “So that would be a line of things to consider” for the Long COVID patient.

The discovery of the SARS-CoV-2 or Epstein-Barr virus in the blood that could predict some cases of Long COVID also suggests that taking antiretroviral medication soon after a COVID-19 diagnosis, he said. may help prevent some cases.

Treatment distance

For now, however, that’s just a theory. Martin from Dartmouth-Hitchcock said that, at least until more research is done, knowing about the risk factors doesn’t do much for people who have had long-term COVID.

Patients often ask about studies they’ve read about risk factors, and all Martin can tell them is, “it doesn’t change the way we manage your symptoms,” she says. . “’What can put you at risk for it, it doesn’t change everything. You have it.'”

Even symptom management, at this point, a complicated game of trial and errorJeffrey Parsonnet, an infectious disease physician who also works at Dartmouth-Hitchcock’s clinic, said. Some of the interventions that seem to work best for patients at his clinic — like occupational therapy and mental health support — don’t have much to do with the basic science described in the studies. . “One of the biggest things we have to offer is a sympathetic and understanding ear,” says Parsonnet.

Dr. Brad Nieset, who runs the Benefis Health System COVID-19 Recovery Program in Montana, says his approach revolves around meeting individual patient recovery goals, whether it be is feeling well enough to sing in church or return to outdoor activities. While his team is always up to date with the latest research, Nieset says it sometimes feels like “people are grabbing zebras.” [rather than looking for horses]. It doesn’t get complicated once you break it down” and focus on what can really help each patient. Often, that means applying long-standing treatments — like respiratory or neurological therapy — to a new illness, he said.

Nieset said that a better understanding of risk factors could be helpful, if vulnerable people can seek care soon after they test positive for COVID-19. But, again, many of the risk factors identified by studies, such as autoantibodies or viral load in the blood, are not something the average person can know they have.

As such, there’s “no direct implications for that,” in terms of developing screening criteria or treatments for patients, Parsonnet said.

Dr Onur Boyman, a clinical immunologist at the University of Zurich, disagrees. He co-authored a recent paper on risk factors for long-term COVID, published in January in Nature Communications. His team found that older people, people with a history of asthma, and people with low levels of certain immunoglobulins (a type of antibody) have a longer risk of developing COVID. People who experience a variety of symptoms during their acute COVID-19 infection are also at higher risk than those with few symptoms.

While most people don’t know much about their immunoglobulin levels, Boyman says the test is fairly easy and inexpensive. “If you have patients who are elderly and/or have a history of asthma, then you can measure their immunoglobulin levels. If those numbers are also relatively low, then you know this individual has a particularly high risk of developing long-term COVID,” he said.

Armed with that knowledge, he says, “you can make sure that individual is very well vaccinated,” perhaps more often. booster shot Boyman said. Studies have shown that vaccinated people get infected about halves the chance of developing long-term COVIDcompared with the unvaccinated.

Going beyond long COVID

Even if studies don’t immediately turn to treatments, it’s important to understand how the disease works and who is affected. That is especially true for a situation as complex as Long COVID; If studies begin to show that there are indeed different subtypes of Long COVID, this could lead to more personalized patient care, Boyman said.

Long-term COVID is also part of a much broader network of chronic diseases. It seems to overlap particularly significantly with myelitis/chronic fatigue syndrome (ME/CFS)—a condition that can follow viral illnesses and lead to debilitating illness—to levels experienced by some persistent COVID patients Diagnostic criteria for ME/CFS.

Complicated chronic conditions like ME/CFS, chronic Lyme disease, and fibromyalgia were around long before COVID-19 existed and affected millions of people in the United States alone, but before that. they do not receive much research funding or interest from mainstream public health. Patient advocate Rivka Solomon, who has had ME/CFS for 32 years, says: “I have a 40-year history defined by neglect and abandonment.

While Solomon says she’s delighted by the amount of interest going into Long COVID and emphasizes that there’s no “we against them” in the chronic disease world, she looks forward to other complex illnesses. received similar attention and funding — like $1.15 billion over four years Congress gave the National Institutes of Health in 2020 to support research on the long-term effects of COVID-19.

Part of the imbalance may have to do with the size and immediacy of the long COVID problem. Experts estimate there are over 15 million long-term COVID patients in the US and even more around the world, all of whom have contracted the disease in the past two years. In contrast, up to 2.5 million ME/CFS patients live in the US. But if researchers had invested in ME/CFS and other post-infectious chronic diseases earlier, Solomon said, they might have better answers for Long COVID patients today.

Heath argues that all the attention on Long COVID could lead to breakouts for other conditions. If researchers learn more about how chronic disease works, over time it could lead to improvements for people living with a variety of illnesses, he said. The study “is not really just about long-term COVID. It is about factors that can lead to the development of chronic diseases.” (Solomon says she’d like to see more studies that focus specifically on conditions like ME/CFS, rather than assuming that long COVID findings translate to other diagnoses.)

Science is making progress, but that progress can feel surprisingly slow for both Long COVID patients and those who have had other viral illnesses before. It can take years for hypotheses to turn into solutions — years for the patient to never return.

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