One of my patients, a 48-year-old mother of two young children, came to see me because she had never fully recovered after getting COVID-19 almost four years earlier. Before becoming ill, she had been active, energetic, and busy raising her family. After COVID, everything changed. She was constantly exhausted, struggled with brain fog, and found it difficult to think clearly or keep up with everyday responsibilities.
Over the years she had tried many natural therapies, including dietary changes, nutritional supplements, gut-healing programs, and supplements designed to support her mitochondria—the tiny energy factories inside our cells. Although some of these approaches helped a little, none produced the significant improvement she hoped for.
As new research began emerging about persistent spike protein, I discussed with her the concept of spikeopathy and recommended a protocol designed to support the body's natural clearance of persistent spike protein while also reducing inflammation, supporting healthy blood vessels, and promoting the normal breakdown of fibrin, the protein involved in blood clotting.
About two months later, she told me that she noticed a clear improvement. Her energy had increased, her thinking was sharper, and she finally felt like she was moving in the right direction. Because she continued improving, we kept her on the program. After six months, she estimated that her fatigue and brain fog had improved by more than 80 percent. She was once again able to enjoy time with her children, be productive throughout the day, and participate in activities she had been forced to give up.
Of course, one patient's experience does not prove that a treatment works. Every person is different, and controlled clinical trials are needed before any therapy can be considered proven. Still, stories like hers remind me why research into long COVID is so important. They also remind me that when conventional medicine has few answers, it is worthwhile to carefully investigate emerging science that may eventually help many more people.
To understand why researchers are paying so much attention to spike protein, it helps to first understand what it actually is.
The spike protein is the crown-like protein that sticks out from the surface of the SARS-CoV-2 virus, the virus that causes COVID-19. Think of it as a key. Its job is to attach to a receptor on the surface of our cells called ACE2, allowing the virus to unlock the cell and enter it.
The mRNA COVID-19 vaccines also use the spike protein—but in a very different way. Instead of exposing the body to the entire virus, the vaccines instruct our own cells to temporarily make copies of the spike protein. The immune system recognizes this protein as foreign and learns to make antibodies and other immune defenses against it. Later, if the real virus enters the body, the immune system is already prepared to respond quickly.
For most people, this process works exactly as intended. The immune system recognizes the spike protein, develops immunity, clears the protein, and the body returns to normal. However, over the past several years researchers have begun asking an important question:
What happens if some spike protein is not cleared as quickly as expected?
That question has become one of the major areas of research in long COVID.
Several researchers have introduced the term spikeopathy to describe the possibility that the spike protein itself may contribute to illness independently of the whole virus.
Originally, scientists viewed the spike protein simply as the "key" that allows the virus to enter our cells. Today, laboratory research suggests that it may be much more than that. Studies indicate that spike protein is biologically active and can interact with many different tissues throughout the body.
Researchers have found evidence that spike protein can affect the lining of blood vessels, activate immune cells, interact with platelets involved in blood clotting, interfere with mitochondria that produce cellular energy, and stimulate inflammatory pathways. Rather than acting in only one organ, spike protein appears capable of influencing several body systems at the same time.
This does not mean that everyone who has COVID-19—or receives an mRNA vaccine—develops spikeopathy. In fact, the overwhelming majority of people appear to clear spike protein normally. Instead, researchers believe that a subset of individuals may not eliminate spike protein as efficiently. In these people, persistent spike protein could become one factor contributing to ongoing inflammation, fatigue, brain fog, muscle pain, blood vessel dysfunction, and other symptoms associated with long COVID.
Spikeopathy remains a scientific hypothesis that is supported by growing laboratory and clinical evidence, but many important questions remain unanswered. Researchers are still working to determine who is at risk, why some people clear spike protein more slowly than others, and exactly how much of a role persistent spike protein plays compared with other contributors such as immune dysfunction, viral persistence, mitochondrial injury, or changes in the nervous system.
One of the biggest questions researchers are trying to answer is whether spike protein completely disappears after COVID-19 or whether it sometimes remains in the body much longer than expected.
The good news is that most people appear to clear spike protein normally. After recovering from COVID-19—or after receiving an mRNA vaccine—the immune system breaks down and removes the spike protein over time. For the vast majority of people, this happens without any ongoing problems.
However, over the past several years, researchers have found evidence suggesting that a small percentage of people may not clear all of the spike protein or viral material as quickly as expected.
For example, scientists have detected spike protein inside certain immune cells called monocytes many months after a COVID-19 infection. These cells normally help the body fight infection by traveling through the bloodstream and into tissues. If they continue carrying spike protein long after the virus is gone, they may also continue stimulating inflammation.
Other studies have found pieces of the virus, including spike protein or viral genetic material, within the lining of the intestines months after the original infection. Researchers sometimes refer to these areas as viral reservoirs, meaning places where remnants of the virus may remain even after a person appears to have recovered. Scientists are still trying to determine whether these viral remnants are capable of causing ongoing symptoms or are simply leftovers from the original infection.
Researchers have also studied what happens after mRNA vaccination. They found that spike protein can remain in nearby lymph nodes for several weeks after vaccination. This is actually considered a normal part of how the immune system develops long-lasting protection. The lymph nodes are like training centers where immune cells learn to recognize the spike protein and produce antibodies and memory cells that can respond quickly if the virus is encountered later.
For people who continue to experience persistent symptoms after COVID-19, researchers have also detected spike protein circulating in the bloodstream or inside immune cells for longer than expected. These findings have led scientists to ask whether delayed clearance of spike protein might contribute to long COVID in at least some patients.
It is important to understand that finding spike protein does not automatically prove it is causing disease. Researchers have identified persistent spike protein in some people who continue to have symptoms, but they have also found that not everyone with persistent symptoms has detectable spike protein, and not everyone with detectable spike protein feels ill. This tells us that long COVID is likely more complicated than any single explanation.
Instead, scientists increasingly believe that persistent spike protein may be one piece of a much larger puzzle. Other factors—including immune system dysfunction, ongoing inflammation, injury to blood vessels, mitochondrial dysfunction, abnormalities in blood clotting, changes in the nervous system, and possibly hidden reservoirs of virus in certain tissues—may all work together to produce the wide variety of symptoms seen in long COVID.
For now, the evidence suggests that persistent spike protein is a plausible contributor to long COVID in some individuals, but much more research is needed to understand exactly how important it is and why it affects some people but not others.
One question researchers have been asking is whether people who have persistent spike protein eventually clear it, or whether it remains indefinitely.
A recent two-year study has provided some encouraging news. Researchers followed people who had recovered from COVID-19, including those with long COVID, and repeatedly measured viral proteins in their blood over time.
During the first year after infection, viral proteins were found much more often in people with long COVID than in people who had fully recovered. This suggests that some individuals may take much longer to eliminate viral proteins from their bodies.
The encouraging finding was that the number of people with detectable viral proteins steadily decreased over time. By about two years after infection, only a small percentage of participants still had detectable viral proteins circulating in their bloodstream.
This suggests that most people eventually clear persistent viral proteins, even if it takes much longer than expected.
Interestingly, the researchers also found that the amount of spike protein in the blood did not always match how sick someone felt. Some people with ongoing symptoms no longer had detectable spike protein, while others with detectable protein had relatively mild symptoms.
This finding tells us something important. Long COVID is probably not caused by just one problem. Persistent spike protein may play an important role in some patients, but other factors—including immune system imbalance, chronic inflammation, injury to the lining of blood vessels, mitochondrial dysfunction, and hidden viral reservoirs within tissues—may continue to drive symptoms even after spike protein can no longer be measured in the bloodstream.
In other words, long COVID appears to be a complex condition with several overlapping causes rather than a single disease with one explanation. That is one reason why different patients often respond to different treatments, and why researchers continue to investigate several possible therapeutic approaches.
If spike protein does remain in the body longer than expected, the next question is obvious:
How could it actually make someone feel sick?
Scientists are still working out the answer, but laboratory studies over the past several years have uncovered several possible ways that spike protein could affect the body.
Originally, researchers believed the spike protein's only job was to help the coronavirus enter our cells. Today, they know it is much more biologically active than they first realized. Studies suggest that spike protein can interact with many different types of cells throughout the body, particularly the cells that line our blood vessels, certain immune cells, and platelets, which help our blood clot.
One area of concern is the endothelium, the thin layer of cells that lines every blood vessel in the body. Healthy endothelial cells help regulate blood flow, keep blood vessels flexible, and control normal clotting. Laboratory studies suggest that spike protein may irritate these cells and reduce their ability to function normally. When blood vessels become irritated, they may become less efficient at delivering oxygen and nutrients to tissues throughout the body.
Researchers have also found evidence that spike protein may increase inflammation. Inflammation is one of the body's normal defense mechanisms against infection and injury. It is essential for healing. However, when inflammation continues for too long, it can begin to damage healthy tissues instead of protecting them. Persistent inflammation has been linked to fatigue, muscle pain, joint aches, headaches, brain fog, and many other symptoms reported by people with long COVID.
Another area of active research involves the mitochondria, often called the "power plants" or "energy factories" of our cells. Mitochondria convert the food we eat and the oxygen we breathe into the energy that every cell needs to function. Laboratory studies suggest that spike protein may interfere with normal mitochondrial function in some cells. If cells cannot produce energy efficiently, it could help explain why many people with long COVID feel exhausted after even minor physical or mental activity.
Researchers have also become interested in the effects of spike protein on fibrin, a protein that helps form blood clots. Normally, the body carefully balances clot formation with clot breakdown. When we cut ourselves, fibrin helps stop bleeding. Once healing occurs, the body naturally dissolves those clots.
Some laboratory studies suggest that spike protein may change the structure of fibrin, making some clots more difficult for the body to break down. Scientists are investigating whether this abnormal clotting process contributes to symptoms experienced by some people with long COVID.
Taken together, these studies suggest that persistent spike protein could affect several body systems at the same time—including blood vessels, the immune system, energy production, and normal blood clotting. Rather than causing one specific symptom, these combined effects may help explain why long COVID can look so different from one person to another.
One of the most exciting discoveries in long COVID research involves tiny blood clots called microclots.
Unlike the large blood clots that can cause strokes or pulmonary embolisms, microclots are extremely small. They are so tiny that they usually cannot be detected with routine blood tests or standard medical imaging. Yet researchers have repeatedly found that many people with long COVID have significantly more of these microscopic clots than healthy individuals.
Why might these tiny clots matter?
Every organ in the body depends on a constant supply of oxygen and nutrients delivered through millions of microscopic blood vessels called capillaries. If even some of these tiny vessels become partially blocked by microclots, oxygen delivery to tissues may be reduced. Muscles, nerves, and the brain are especially sensitive to even small reductions in oxygen supply.
Researchers believe this could help explain why many people with long COVID experience profound fatigue, poor exercise tolerance, muscle pain, dizziness, shortness of breath, and brain fog—even though routine medical tests often appear normal.
Scientists have also discovered that these microclots are often mixed with sticky webs released by white blood cells called neutrophil extracellular traps, or NETs.
NETs are actually part of our normal immune defense. When certain white blood cells encounter bacteria or viruses, they can release these web-like structures to trap invading microbes and help destroy them. Under normal circumstances, this is a useful part of the immune response.
The problem occurs when too many NETs are produced or when they are not cleared efficiently.
Instead of protecting the body, excessive NET formation may increase inflammation and make it easier for abnormal clots to develop. Researchers now believe that inflammation, NETs, platelets, fibrin, and the lining of blood vessels may all interact with one another, creating a cycle that becomes difficult for the body to shut off.
This is one reason why long COVID appears to involve much more than lingering fatigue. Many researchers now think it may represent a complex disorder involving the immune system, blood vessels, inflammation, and abnormal clotting all occurring together.
Although the microclot theory has generated tremendous interest, many questions remain unanswered. Scientists are still trying to determine whether microclots are a primary cause of symptoms or simply another sign that inflammation is ongoing. They are also studying whether therapies that support the body's normal ability to break down fibrin and restore healthy circulation can improve symptoms in some patients.
Like many areas of long COVID research, this field is advancing rapidly. While more clinical trials are needed, the discovery of microclots and NETs has provided researchers with another important clue that may eventually lead to more effective treatments.
One of the most frustrating symptoms reported by people with long COVID is brain fog. Many patients describe difficulty concentrating, forgetting words, losing their train of thought, or feeling as though their brain is working in slow motion. Others develop headaches, dizziness, poor sleep, anxiety, or increased sensitivity to light and noise.
For years, doctors struggled to explain these symptoms because brain scans often looked normal. Now, laboratory research is beginning to provide some possible answers.
The brain has its own immune cells called microglia. Think of microglia as the brain's housekeeping and security team. Under normal conditions, they help remove damaged cells, fight infections, and keep the brain healthy.
When an infection or injury occurs, microglia become activated to protect the brain. Normally, once the threat is gone, they settle back down.
Laboratory studies suggest that spike protein may activate these microglial cells. When activated for prolonged periods, microglia release inflammatory chemicals that can interfere with normal communication between brain cells.
Researchers believe this ongoing inflammation could help explain why some people experience persistent brain fog, poor concentration, headaches, memory problems, dizziness, and sleep disturbances after COVID-19.
Scientists also believe that brain inflammation is probably only one part of the picture. Reduced blood flow from microclots, injury to the lining of small blood vessels, persistent immune activation, mitochondrial dysfunction, and other inflammatory processes may all work together to affect brain function. This may explain why neurological symptoms vary so much from one patient to another.
As research into persistent spike protein has grown, many patients have asked whether there are natural therapies that might help.
One supplement receiving considerable attention is nattokinase.
Nattokinase is a natural enzyme produced during the fermentation of soybeans into the traditional Japanese food called natto. In Japan, natto has been eaten for centuries and is considered a healthy food.
Scientists have studied nattokinase because it has the ability to help break down fibrin, the protein that forms the framework of blood clots. This has made researchers interested in whether it might also help support the body's normal breakdown of the abnormal fibrin seen in laboratory studies of long COVID.
Even more intriguing, laboratory experiments have shown that nattokinase can directly break down spike protein in test tubes. These findings have generated considerable interest among both researchers and integrative physicians.
Some clinicians have suggested combining nattokinase with bromelain, an enzyme extracted from pineapple, and curcumin, the active compound found in turmeric. Bromelain has anti-inflammatory properties and may also support normal fibrin metabolism, while curcumin has been extensively studied for its ability to reduce inflammation and help regulate immune function. Together, these supplements may work through different mechanisms that complement one another.
Although these findings are encouraging, it is important to understand their limitations.
At the present time, there are no large, well-designed human clinical trials proving that nattokinase removes persistent spike protein or reliably improves long COVID symptoms. Most of the current evidence comes from laboratory studies, theoretical mechanisms, small clinical experiences, and observations from physicians treating patients.
That does not mean nattokinase cannot help. It simply means the scientific evidence has not yet reached the level required to draw firm conclusions. Clinically, I do find nattokinase helps quite a few patients.
Patients should also remember that anyone on blood thinning medications or those scheduled for surgery should check with their healthcare providers before using it.
One of the biggest lessons we have learned about long COVID is that there is probably no single cause and no single treatment.
Some people appear to have persistent viral proteins. Others seem to have immune system imbalance, chronic inflammation, mitochondrial dysfunction, injury to blood vessels, abnormal clotting, disturbances in the nervous system, or a combination of several of these problems.
This helps explain why one treatment may work well for one patient but have little effect in another.
From an integrative medicine perspective, the goal is not simply to suppress symptoms but to support the body's natural ability to heal.
That often begins with reducing inflammation through an anti-inflammatory diet rich in vegetables, fruits, healthy fats, legumes, nuts, seeds, herbs, and spices while minimizing highly processed foods and excess sugar. Correcting nutritional deficiencies—including vitamin D, magnesium, zinc, omega-3 fatty acids, B vitamins, and other nutrients when appropriate—may also support immune function and recovery.
Supporting healthy blood vessels and normal circulation is another important goal. Regular movement, when tolerated, adequate hydration, good sleep, stress reduction, and carefully selected nutritional supplements may all play a role in restoring normal physiology.
Improving mitochondrial function is equally important because healthy mitochondria provide the energy needed by every organ in the body. Addressing gut health, optimizing the intestinal microbiome, and treating persistent inflammation may also support overall recovery.
No single therapy is likely to help everyone. Instead, successful treatment usually requires looking at the whole person, identifying the factors contributing to illness, and developing an individualized plan that addresses those specific problems.
As our understanding of long COVID continues to improve, integrative medicine offers a framework that combines lifestyle medicine, nutrition, targeted supplements, conventional medical care, and emerging scientific evidence to support the body's remarkable ability to heal.
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