It has been more than two years since long COVID manifested, and scientists are still far from settled on its cause.
Spike Protein Appears to Be the Leading Contributor
Spike protein can exist in the immune cells of long COVID patients for up to 15 months after infection.The spike protein sits on the surface of the COVID-19 virus and is the key to breaking into cells and causing the virus to spread in organs and tissue.
However, the symptoms and laboratory test results vary depending on the patient. Clinicians have therefore developed various hypotheses on the reasons behind these symptoms.
1. Inflamed Immune Cells and Blood Vessels
The spike protein contributes to pathologies. The primary pathology is inflammation (1, 2, 3).Inflammation is not harmful if controlled and short-term; it is essential to a person’s immune defense. But in the case of long COVID, inflammation is chronic, and this causes cells to become stressed and damaged.
When interviewed by The Epoch Times, Dr. Bruce Patterson, a viral pathologist and the CEO and founder of IncellDx, a diagnostic company, and internal medicine physician Dr. Jessica Peatross each pointed out the relationship between inflammation and long COVID.
She pointed to studies on acute COVID as a systemic disease driven by inflammation of the lining of the blood vessel walls.
Inflammation of blood vessels can reduce blood flow to tissues and organs, causing pain and impaired organ function. Low blood flow also means fewer nutrients are supplied to the cells, causing fatigue and weakness.
Unsurprisingly, significant symptoms of inflammation in blood vessels are fatigue, and joint and muscle pain, which overlap with long COVID symptoms.
Symptoms vary depending on where the inflammation occurs.
Vascular inflammation in the superficial layers of the skin may cause clusters of red dots, bruises, or hives.
Inflammation in blood vessels that supply the eyes may cause the eyes to become sensitive to light or even cause vision impairment.
2. Mitochondrial Dysfunction
California physician Dr. Jeffrey Nordella told The Epoch Times that mitochondrial dysfunction is another major contributor to long COVID symptoms.It should be noted that all of the symptoms, from inflammation to mitochondrial dysfunction, can overlap. Mitochondria can become stressed from low oxygen due to blood vessel inflammation or nearby inflammation.
Mitochondria are present in practically all cells in the body. Mitochondria make energy for the cell by concurrently burning fuel—carbohydrates, proteins, and fats—and consuming oxygen. However, this process can also produce toxic oxygen species that are highly reactive and damaging to mitochondria.
3. Inflammatory Allergic Response
Mast cells, which are involved in allergies, may contribute to long COVID symptoms.Mast cells are highly reactive, like many immune cells. They carry ACE2 receptors, which allow entrance to the virus or spike protein. Once activated, mast cells can send vast amounts of histamine and inflammatory cytokines into circulation.
Histamine also causes many allergic symptoms, leading to swelling, redness, pain, and fever in the regions of its release.
Many of these symptoms overlap with long COVID symptoms.
Psychiatrist Dr. Adonis Sfera, who has led several studies on COVID-19, said that there might be shared pathways between long COVID and mast cell disorders.
Some studies have shown that COVID-19 patients on drugs that block mast cell activation did better than patients who were not on such drugs.
4. Gut Dysbiosis
Gut dysbiosis, an imbalance of the microbes in the gut, has been extensively documented with long COVID, sometimes occurring for several months (1, 2, 3).Gastroenterologist and CEO of Progenabiome Dr. Sabine Hazan runs a research lab and conducts fecal tests for long COVID patients.
She found that these patients carried COVID-19 genetic material in their guts months after the initial infection. Their gut microflora would be in a state of imbalance called dysbiosis.
Dysbiotic guts can lead to gastrointestinal symptoms such as diarrhea, constipation, bloating, abdominal pain, and indigestion.
Gut dysbiosis is also associated with chronic diseases such as poor mental health, obesity, diabetes, cancer, and cardiovascular disease.
The gut plays a critical role in physical well-being. A consequence of gut dysbiosis is the breakdown of the gut barrier (a condition called “leaky gut”). Bacteria can leave the gut and enter the bloodstream, leading to an immune response.
Sfera said that many bacteria in the gut are similar in structure to the body’s own cells. So when the immune system attacks bacteria, it may also mistake healthy tissues for bacteria, triggering an “autoimmune inflammation, in which the body attacks itself.”
Some Reported Symptoms May Not Be From Long COVID
Patterson’s studies on cytokines suggest that many people who report “long COVID” symptoms may not be experiencing long COVID but rather a reactivation of latent viruses.A patient, Mary Lee, had been experiencing long COVID symptoms since December 2021.
Her cytokine test revealed elevated cytokine levels with results indicating long COVID. However, a subsequent blood test showed that she was also positive for Lyme disease.
Lee has been suffering from migraines and fatigue for many years. She suspects that her untreated Lyme disease contributed to developing long COVID.
The cause of long COVID is far from settled, and a great deal of the evidence clinicians use to support their hypotheses is anecdotal. Given its complicated clinical symptoms, research will likely continue for many years.