Long COVID: are we on the verge of a breakthrough?

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long COVID research

When the World Health Organization declared the coronavirus outbreak a global pandemic in early 2020, little did we know that it would dominate the rest of the year and the years to come. Now, almost four years and several vaccines later, research has found that many people infected with the virus feel better in a week or so. But not all. Those with long COVID can have symptoms that last for months and, sometimes, even years. Although, recent advancements in long COVID research suggest that things could change for the better.

How does long COVID manifest in the body?

The Centers for Disease Control and Prevention in the U.S. describes long COVID as a wide range of new, returning, or ongoing health problems that people experience after being infected with the virus that causes COVID-19. There are no tests that can tell if your symptoms are an effect of long COVID but a doctor would diagnose it based on one’s medical history and a health examination.

Studies have shown that those who haven’t gotten a COVID vaccine are more likely to develop long COVID. To add to that, people who are reinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – a viral strain that causes COVID – have a higher risk of developing long COVID, and with each recurrence, the likelihood increases. 

In the U.S., long COVID has been recognized as a condition that could result in a disability under the Americans with Disabilities Act (ADA), since 2021.

While there isn’t one specific medicine that can cure long COVID, a recent study hints at broadening treatment approaches and potentially expanding diagnostic tools.

The complement system and long COVID

The study published in Science, which examined the body’s immune response to long COVID, has to do with the complement system. The complement system is a network of proteins that are activated when a pathogen enters the body. Some of the proteins tag the pathogen to trigger its destruction. When the complement system is alerted, it leads to a cascade of inflammatory reactions that help fight infection.

The study involved 113 people who had been infected with COVID as well as 39 people in the control group. Out of the 113 patients, 40 developed symptoms of long COVID, at the end of six months. Blood samples from those who experienced long COVID showed that the complement system didn’t switch off after the virus entered the body, despite it being cleared out of the body.

Typically, the complement system returns to its resting phase once it has eliminated the pathogen that attacked the body. Scientists found that in the case of long COVID, when the complement system is continuously on duty, it begins damaging healthy cells and tissues. These can even be cells in different organs like the lungs or the brain. 

This might be indicative of why patients with long COVID continue to experience brain fog, fatigue and breathing issues.

Long Covid was linked to clusters of monocytes and platelets as well as tissue injury, the study explained. This study piles on to the need for further research into complement modulators – which can help mitigate cell and tissue damage – and clinical trials testing new biomarkers in long COVID.

While this study can help ramp things up on the complement system research front, the U.S. National Institutes of Health’s (NIH’s) RECOVER initiative is also dedicated to long COVID research.

Recovering from COVID: the NIH’s role

As part of the project, researchers are conducting autopsies – a medical exam of a body after death – and taking tissue samples from people who have died from COVID, including long COVID. The aim of this is to identify how long COVID affects the different parts of the body.

Focused on solving the root cause of long COVID, and why some people get it and some don’t, the RECOVER clinical trials are currently enrolling participants for their study. Phase 2 trials aim to explore treatments for autonomic dysfunction, which includes a range of symptoms like dizziness, shortness of breath and an upset stomach, as well as cognitive dysfunction, which include brain fog and memory-related problems. The trials also look to improve sleeping patterns, manage fatigue, and most importantly, tackle viral persistence, a major driver of long COVID. This occurs when a virus, in this case, the coronavirus, continues to live in the body and cause damage to the immune system.

In these trials, various treatments like drugs, biologics, and medical devices will be tested for long COVID.

While the U.S. government has shelled out more than a billion dollars to help people struggling with long COVID symptoms, a report published in The Sick Times that interviewed Eric Topol, founder and director of the Scripps Research Translational Institute, claims that the Biden administration failed to recognize the long COVID crisis early on in the U.S. Moreover, some critics have said that the NIH’s efforts to curb the spread of COVID – in particular, learn more about long COVID in order to treat the prolonged symptoms that come with it – are moving at a snail’s pace. 

An article by Stat revealed that the NIH RECOVER funds were spent disproportionately, with observational studies bagging much more than clinical trials, which cost around $170 million. And, as the U.S. government has overlooked long COVID research in their $5 billion program to develop COVID-19 vaccines and treatments, some researchers demand that the White House needs to pour more money into the field.

What steps are being taken in the U.K. to prevent long COVID?

However, in other parts of the world, there seems to be some progress. In the U.K., a nation-wide study, STIMULATE-ICP, is recruiting more than 4,500 people in what is the largest long COVID trial to date. A phase 3 trial to evaluate the effectiveness of existing drugs in treating long COVID after three months of treatment, will begin soon. The results will be based on how much the patients’ symptoms have improved, as well as measure how it has affected their mental health. 

The mental health of people with long COVID is said to worsen with time, according to research. A study conducted by Imperial College London, found that mental health and health-related quality of life were worse among patients who experienced persistent symptoms post-COVID compared with those who had never had COVID-19 or those who had recovered from the infection. 

The STIMULATE-ICP program is currently ongoing at the University College London Hospitals NHS Trust, and will also test whether magnetic resonance imaging (MRI) scans can aid in diagnosing potential organ damage, and focus on rehabilitation through an app that can track patients’ symptoms.

Diagnostic and therapeutic research into long COVID

Meanwhile, biomarker research is helping identify better tools for long COVID diagnosis. Elevated levels of extracellular vesicles – components that carry molecules in and out of cells – is a sign of long COVID as it indicates high cytotoxicity. Also, studies have hinted that biomarker tests in myalgic encephalomyelitis/chronic fatigue syndrome, a condition that causes extreme tiredness in people, could be used to detect long COVID as well. This may be done via blood and saliva tests, and sex-specific plasma lipid profiles.

One discovery that some may find fascinating, is that dogs are capable of identifying people with long COVID by merely smelling sweat samples. A study revealed that the dogs sniffed out positive samples from more than half of the patient cohort that had long COVID. While patients will probably need further tests to confirm their diagnosis, this non-invasive method is fairly quick and highly sensitive, research suggests.

To add to that, the antiviral drug Paxlovid has been tied to lowering the risk of developing long COVID. The drug slashed the chances of people getting long COVID by 25%, according to a study. Paxlovid comprises nirmatrelvir and ritonavir. Nirmatrelvir binds to the active site on the virus to halt its replication process, and ritonavir, in turn, ​​guards nirmatrelvir and ensures that it does not get broken down before it has attacked the virus.

While studies are currently being held in the clinic to figure out the best ways to beat long COVID, it seems like much more research needs to be done to address possible solutions to conquer the disease. And, for starters, filling up the funding pot could help with it.

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