January 6, 2023 – While the causes of Long COVID remain unclear, researchers are specializing in biomarkers – detectable and measurable compounds – that may help them higher diagnose and treat the disease. The ultimate goal: an easy test to assist determine who has Long COVID and whether treatments will help.
“The hope is that the specific markers discovered will provide insight into how individual disease clusters should be treated and managed to either reduce or eliminate symptoms,” says David WaltPhD, Co-Director of Mass General Brigham Center for COVID Innovation in Boston.
Biomarkers are widely used to discover and track diseases, starting from easy measurements like blood pressure or blood sugar levels to the autoantibodies that cause rheumatoid arthritis and the enzymes that may indicate liver disease. Since the unbearable symptoms of long-COVID include fatigue, shortness of breath, chest pain and dizziness, knowing a number of biomarkers could help higher define and diagnose the disease.
Michael Peluso, MD, who has been treating COVID-19 and long-COVID patients at San Francisco General Hospital because the starting of the pandemic, says a “game-changing” biomarker can be “finding something where you can intervene today, see a change in marker levels, and know that this is going to have long-term implications.”
Researchers know that patients shouldn’t expect a single diagnostic test or research standard to emerge. Several things appear to be related to different symptoms. Scientists and doctors expect they may establish different clinical subtypes of Long COVID.
Many research teams work under the umbrella of the RECOVER initiativea $1.15 billion long-term COVID project of the National Institutes of Health. The NIH has 40 research projects Investigating the role of metabolism, genetics, obesity, antibodies, inflammation, diabetes and more.
The NIH team has divided Long COVID into Symptom cluster and appears for the causes of diseases in each cluster. The clusters are:
- Viral persistence: When the COVID-19 virus stays in some people’s bodies
- Autonomic dysfunction: Changes in the flexibility to control heart rate, body temperature, respiration, digestion and sensory perception
- Sleep disorders: changes in sleep patterns or ability to sleep
- Cognitive dysfunction: problems considering clearly or brain fog
- Exercise intolerance/fatigue: Changes in an individual’s activity and/or energy levels
The RECOVER studies The first clinical trials are expected to start in early 2023. The first clinical trial will test the antiviral Paxlovid, which has some Efficacy in early studies – against a placebo.
Many researchers are gathering evidence that the virus hiding in patients' bodies is answerable for Long COVID. This could make the virus itself or parts of it a biomarker for Long COVID.
Walt from Mass General used a Sensitive test that would find much smaller parts of the virus than conventional tests. In a sample of about 50 patients 65% of Long-COVID patients found had parts of the spike protein of the SARS-CoV-2 virus of their blood. Although the study was small and preliminary, he sees the presence of the spike protein within the blood as a sign.
“If there were no virus, there would be no spike protein, because the lifespan of the spike protein is very short after someone has overcome their viral infection,” says Walt. “In order for this spike to continue to circulate, it must be continuously produced from active viruses.”
A personal research collective in California is in search of the persistent presence of the virus in organ tissues. Researchers on the PolyBio Research Foundation are studying complex chronic inflammatory diseases reminiscent of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and now Long COVID, which frequently produces the identical symptoms.
Michael VanElzakkerPhD, co-founder of the group and a member of the Department of Neurotherapy at Massachusetts General Brigham Hospital in Boston, is targeted on the potential of a viral reservoir – a spot where the virus can hang around and evade the immune system. If there’s a reservoir there, his team wants to search out it and determine what it's doing, VanElzakker says.
“All successful pathogens evade the immune system in some way,” he says. “They can't find small niches where they can do this well.”
Microclots – small blood clots – are one other sign of Long COVID. A gaggle of researchers – #TeamClots on Twitter – is investigating them. One theory is that inflammation promotes the formation of blood clots, which destroy tiny blood vessels and stop oxygen from reaching them. Possible trigger: The spike protein.
Signs of inflammation could themselves be used as biomarkers. Peluso and colleagues present 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 Updated 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 ever-new COVID variants has complicated research. Much of the early research was done before the emergence of the omicron variant. Walt said he found spike protein in fewer omicron long-COVID samples — more like 50% than 65% — and researchers found fewer blood clots in omicron patients. who also had a milder illness.
Like another scientists studying Long COVID, Dr. Mohamed Abdel-Mohsen began studying one other virus, in his case HIV. It can sometimes damage the intestinal lining and lead to what’s often known as leaky gut syndrome. Abdel-Mohsen, a Associate Professor on the Vaccine & Immunotherapy Center on the Wistar Institute in Philadelphia suspected that long-COVID patients could also suffer from leaky gut syndrome.
Abdel-Mohsen and colleagues found Evidence that microbes have leaked from the heart of long-term COVID patients and caused inflammation elsewhere within the body, possibly including the brain. But it's possible to treat this condition with drugs, he says. Looking for evidence of such leakage could provide not only a biomarker but in addition a goal for treatment.
“There are many ways to intervene therapeutically and hopefully alleviate the symptoms and improve the condition of people suffering from Long COVID,” he says.
Biomarker research remains to be in its early stages, but there’s hope of finding a biomarker that indicates a treatment.
“T“The holy grail of biomarkers is surrogate markers,” Peluso said during the RECOVER briefing in November. “With a surrogate marker, it's about identifying the marker, identifying the extent of the marker, after which doing something to alter that. And changing the extent of the biomarker results in a change within the clinical consequence.”
In other words, it’s something much like a statin drug that lowers the extent of bad cholesterol, which in turn reduces the speed of stroke and heart attack.