February 1, 2023 – Constant inflammation and immune problems top the list of possible causes of Long COVID, but doctors say it's becoming increasingly clear that multiple thing is accountable for the wide selection of often debilitating symptoms that may last for months and even years.
“I think it's a much more complex picture than just inflammation, autoimmunity or immune deficiency. And it's probably a combination of all three that triggers a cascade of effects that then manifests as brain fog, shortness of breath or chronic fatigue,” says Dr. Alexander Truong, a pulmonologist and assistant professor at Emory University School of Medicine who also runs a Long COVID clinic.
Long COVID, post-COVID-19 state and post-acute sequelae of SARS-CoV-2 (PASC) are a few of the terms utilized by the National Institute of Health to explain the long-term health problems which can be estimated to affect 10% to 30% of individuals infected with COVID-19. Symptoms – up to 200 – can range from uncomfortable to debilitating, damage multiple organ systems, come and go, and relapse. Long COVID increases the chance of worsening existing health problems and trigger newincluding heart problems and sort 2 diabetes.
Research so far suggests that there isn’t a single cause, condition or disease that explains why some people experience a wide selection of symptoms long after the early COVID-19 infection has subsided. Many experts consider that a mixture of biological processes – including the virus floating around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems and even the Reactivation of dormant viruses similar to the Epstein-Barr virus – could possibly be the wrongdoer, a theory that can be supported by a comprehensive and in-depth review of long-term studies on COVID published in January within the Journal Nature Reviews Microbiology.
“In recent years it has become clear that there are different [symptoms] of Long COVID … you can't lump them all together,” says Michael Peluso, MD, assistant professor of medicine and infectious disease physician at the University of California, San Francisco.
Inflammation and a virus that is haunting
Several studies have shown that the virus or parts of it can persist in many parts of the body long after early infection, including the kidneys, brain, heart and gastrointestinal tract.
“An important question that I think is currently being most intensively investigated is whether there is viral persistence that leads to immune dysregulation and thus to the symptoms,” says Peluso.
A small Harvard University For example, a study published in September found evidence that reservoirs of the coronavirus may be present in patients for up to a year after initial diagnosis.
A former German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body's immune system what to do and are involved in the growth and activity of immune system cells and blood cells. The researchers said the findings supported the theory that there is ongoing reprogramming of certain immune cells and that the uncontrolled “self-sustaining hyperinflammation” during early COVID-19 infection may lead to persistent immune cell dysfunction, resulting in long COVID symptoms.
“Long COVID is more likely due to an inflammatory response in the body or reservoirs of virus that the body is still trying to clear … and the symptoms we're seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.
Australian researchers also found Immune system recovery appeared to be different compared to those infected with other common coronaviruses.
These findings also support concerns raised by some experts about the long-term risks of COVID-19 infections in general, particularly repeated infections.
“Anything that fuels inflammation in the body can cause it to boil over and make symptoms worse. It's very easy to be an infection or some other damage to the body. So that's the general hypothesis as to why damage to the body can make symptoms worse,” Truong says.
An autoimmune disease?
But inflammation alone does not fully explain the problems after COVID-19.
For example, Truong and his team have documented inflammatory markers in patients at the post-COVID clinic he co-founded more than two years ago at Emory Executive Park in Atlanta. When the clinic opened, long-COVID patients were prescribed high-dose nonsteroidal anti-inflammatory drugs, known as NSAIDs — including ibuprofen — and prednisone.
“It hasn't made any difference at all for any of these people,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it's too early to treat long-COVID patients with drugs used for other autoimmune diseases.
In autoimmune diseases such as rheumatoid arthritis, lupus and type 1 diabetes, a person's immune system does not distinguish normal cells from foreign pathogens and attacks healthy cells. There is usually no single diagnostic test, and many have similar symptoms, making detection and diagnosis potentially difficult, so Johns Hopkins Medicine.
A small study Published in the diary Science Translational Medicine In December, it emerged that patients who did not regain their sense of smell long after the initial infection experienced inflammation in the nasal tissue where the olfactory nerve cells are located, even though the virus was no longer detectable. Fewer olfactory sensory neurons were also observed – findings that researchers said resembled a type of “Autoimmune-like process.”
Meanwhile, scientists in Canada found signs of autoimmunity in blood samples from patients who still suffered from fatigue and shortness of breath after their first COVID-19 infection. Two specific proteins were present in as much as 30% of patients a 12 months after infection, a lot of whom still suffered from shortness of breath and fatigue, the researchers reported within the January 1st Problem of European Journal of Respiratory DiseasesThese patients were healthy before infection and had no autoimmune or other diseases.
Problems with the immune system
Numerous studies suggest that a problematic immune response could also explain why symptoms persist in some people.
Researchers in FranceFor example, found that immune response problems in patients with severe COVID-19 infections caused exaggerated or uncontrolled formation of a sort of pathogen-fighting defense mechanism called neutrophil extracellular traps (NETs), which in turn trigger harmful inflammation that may result in multiorgan damage. These traps are web-like structures manufactured from fibers composed primarily of DNA strands that bind or capture pathogens.
Long COVID isn’t like an acute infectious disease, says Dr. Alexander Charney, the lead investigator of the RECOVER adult cohort at Mount Sinai in New York City and an associate professor on the Icahn School of Medicine at Mount Sinai. It is more like other complex chronic diseases which have taken many years to grasp, similar to heart disease, mental illness and rheumatologic diseases, he says.
Biomarkers and blood clots
Scientists are Focus on biomarkersor detectable and measurable features – on this case, molecular indicators – that may facilitate the diagnosis of Long COVID and supply higher treatment direction. These biomarkers are also key to understanding the complex biology of Long COVID.
In a study, data from blood samples from lots of of hospitalized COVID-19 patients suggest that changes occur on the molecular level through the first severe infections. These changes could also be linked to the event of longer-term symptoms, based on the study. published in December by Charney and his team at Mount Sinai.
Problems with blood clotting have also been present in patients with long Covid. a study found evidence that patients with long COVID had higher levels of a sort of autoantibody related to the abnormal formation of blood clots. Researchers suspect that tiny, stubborn microclots – undetectable by conventional pathology tests – may interrupt oxygen supply to tissues by blocking capillaries – billions of small, fantastic blood vessels throughout the body – and will explain lots of the post-COVID symptoms described by patients.
Although tremendous progress has been made in understanding Long COVID, research remains to be in its early stages and faces many challenges, including different criteria for outlining the disease, the kind and quality of knowledge used, differences in defining and recruiting patients, and the small size of many studies. Some research also appears to contradict others. And although there are specific tools for diagnosing some points of the disease, Standard tests often do not detect lots of the symptoms seen in patients with long COVID-19. But given the urgency and global scale of the issue, experts say more resources and support needs to be made available.
“People are suffering now and they want answers right now… it's not like COVID, where the path to a great and meaningful solution to this incredible problem was clear – we need a vaccine,” Charney says.
“It's going to be a long road to figure out what's going on.”