Researchers Chase Biomarkers – Potential Keys to Long COVID
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January 6, 2023
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January 6, 2023 – Even as the causes of a long COVID remain confusing, researchers are focusing on biomarkers – compounds that can be detected and measured – that may help them better diagnose and treat the condition. The ultimate goal: a simple test to determine who has had COVID for a long time and whether treatments are helping.
“The hope is that the specific markers discovered will shed light on how individual (disease) clusters should be treated and managed to either reduce or eliminate symptoms,” she says David WaltersPhD, Co-Director of Mass General Brigham Center for COVID Innovation in Boston.
Biomarkers are widely used to identify and track diseases. They range from simple measurements like blood pressure or blood sugar levels to the autoantibodies that cause rheumatoid arthritis and the enzymes that can indicate liver disease. As COVID’s unbearable range of symptoms includes fatigue, shortness of breath, chest pain and dizziness, a biomarker or biomarkers could help better define and diagnose them.
Michael Peluso, MD, who has been treating COVID-19 and long-COVID patients at San Francisco General Hospital since the pandemic began, says a “game-changing” biomarker would be to “find something where you can intervene today, see a change in marker level and know that this will have a long-term impact.”
Researchers know that patients should not expect a single diagnostic test or research metric to come out. Several things seem to be linked to different symptoms. Scientists and doctors predict that they will establish different clinical subtypes of long COVID.
Many research teams work under the umbrella of the RECOVER initiative, a $1.15 billion COVID project by the National Institutes of Health. The NIH funded 40 research projects Look at the role of metabolism, genetics, obesity, antibodies, inflammation, diabetes and more.
The NIH team has long divided COVID into symptom cluster and looks for what drives the disease in each cluster. The clusters are:
- Viral persistence: when the COVID-19 virus remains in some people’s bodies
- Autonomic Dysfunction: Changes in the ability to regulate heart rate, body temperature, breathing, digestion, and sensation
- Sleep Disorders: Changes in sleep patterns or ability to sleep
- Cognitive dysfunction: Difficulty thinking clearly or brain fog
- Exercise intolerance/fatigue: Changes in a person’s activity level and/or energy level
the RECOVER studies are expected to begin in early 2023. The first clinical trial will test the antiviral Paxlovid – as some have indicated Efficacy in early studies – against a placebo.
Many researchers are accumulating evidence that the virus hiding in patients’ bodies is long driving COVID. That could make the virus itself or parts of it a biomarker for long COVID.
Mass Generals Walt uses a sensitive test that could find much smaller pieces of the virus than traditional tests. In a sample of about 50 patients, he found 65% of long COVID patients had parts of the spike protein of the SARS-CoV-2 virus in the blood. Although the study was small and preliminary, he sees the presence of the spike protein in the blood as a clue.
“If there weren’t a virus, there wouldn’t be a spike protein because the lifespan of the spike protein is very short after someone clears their viral infection,” says Walt. “There has to be a continuous production of this spike protein from active virus for this spike to keep circulating.”
A private research collaboration in California is looking for the persistent presence of the virus in organ tissues. Researchers at the PolyBio Research Foundation are studying complex chronic inflammatory diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and now long-standing COVID, which often produce the same symptoms.
Michael Van Elzakker, PhD, co-founder of the group and member of the Department of Neurotherapeutics at Massachusetts General Brigham Hospital in Boston, focuses on the possibility of a viral reservoir — a place where the virus can reside and evade the immune system. If it’s there, his team wants to find it and figure out what it’s doing, VanElzakker says.
“All successful pathogens somehow evade the immune system,” he says. “You don’t find little niches where they do that very well.”
microclumps – small blood clots – are another sign of a long COVID. A group of researchers – #Teamclots on Twitter – studying them. One theory is that inflammation encourages blood clots, which disrupt tiny blood vessels and prevent oxygen delivery. One possible trigger: the spike protein.
sign of inflammation could themselves be used as biomarkers. Peluso and colleagues found in 2021 that long COVID patients had higher levels of inflammation Chemicals called cytokines. Measuring these cytokines helps explain the causes of long COVID, Peluso said during a Online RECOVER initiative Update in November.
Similarly, Yale researchers reported in August that cortisol – a stress hormone – was consistently lower than normal in long COVID patients.
The emergence of new COVID variants has made research difficult. Much of the early research was done before the rise of the Omicron variant. Walt said he found spike protein in fewer omicron-long COVID samples — closer to 50% than 65% — and researchers found fewer clots in omicron patients. who also had a minor illness.
Like some of the other scientists who have long focused on COVID, Mohamed Abdel-Mohsen, PhD, began studying a different virus, in his case HIV. It can sometimes damage the lining of the gut, resulting in what is known as leaky gut. Abdel Mohsen, a Associate Professor at the Vaccine & Immunotherapy Center at the Wistar Institute in Philadelphia, thought for a long time that COVID patients could also have leaky gut syndrome.
Abdel-Mohsen and colleagues found Evidence that microbes had leaked from the guts of long COVID patients and were causing inflammation elsewhere in the body, including perhaps the brain. But it’s possible to treat this condition with medication, he says. Looking for signs of such a leak could provide not only a biomarker but also a target for treatment.
“There are many steps to take to therapeutically intervene and hopefully reduce symptoms and improve the quality of people experiencing (long COVID),” he says.
While biomarker research is still in its early stages, the hope is to find a biomarker that points to treatment.
“TThe holy grail of biomarkers really are surrogate markers,” Peluso said during the RECOVER briefing in November. “A replacement marker means you identify the marker, identify the level of the marker, and then do something to change that. And changing the level of the biomarker leads to a change in the clinical outcome.”
In other words, something similar to a statin drug that lowers levels of bad cholesterol — something that in turn lowers stroke and heart attack rates.
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