Can Long COVID Trigger Lyme Disease Flare-Ups?

Learn how long COVID may reactivate Lyme disease and other chronic infections, causing symptoms like fatigue, brain fog, and pain.

Persistent, overwhelming fatigue, cloudy thinking, shortness of breath, body aches and pain—these troubling symptoms are the telltale signs of long COVID.

Yet, for an individual who has previously had a Lyme disease infection, the symptoms may be indicative of COVID-induced Lyme flare-ups—as long COVID symptoms and Lyme disease look alike. Or for someone who at some point in the past experienced an Epstein-Barr virus (EBV) infection or chronic fatigue syndrome (CFS), the symptoms may be a result of chronic illness triggers after COVID.

Indeed, nearly five years after the COVID-19 virus arrived in the U.S., scientists are still making discoveries about the long COVID immune response—and, specifically, COVID and immune system reactivation.

Here’s what you need to know how COVID impacts chronic illnesses and Lyme disease relapse after COVID.

A compromised long COVID immune response could leave an opportunity for previously dormant viral or bacterial infections to re-emerge.

WHAT IS LONG COVID?

Long COVID – also known as post-COVID condition – is a syndrome that occurs in individuals with a history of likely or confirmed SARS CoV-2 infection, usually about three months from the onset of COVID-19. 

Long COVID comes with an array of symptoms that last for at least two months and cannot be explained by an alternative diagnosis to be considered long COVID. The most common symptoms may include any of the following:

These symptoms often have an impact on everyday functioning. Symptoms may appear for the first time following initial recovery from an acute COVID-19 episode, or they can persist from the time of the initial illness. Additionally, they may vary or relapse over time.

One of the most recent scientific surveys of nearly 30,000 participants revealed that about 8% of U.S. adults reported having ever had long COVID. Just under 4% of U.S. adults reported currently having the condition or currently having activity-limiting long COVID.

Of course, the SARS CoV-2 infection is the original initiator of long COVID, but more research is needed to fully understand what transpires at the cellular and molecular levels that brings about long COVID health complications and symptomology.

WHAT DRIVES LONG COVID?

Scientists see long COVID more as an umbrella term because it appears there are likely multiple mechanisms that lead to its development and these conditions are not mutually exclusive—and may even coexist.

According to 2023 research, the leading theories about what drives long COVID include damage/alteration to the immune system, the persistence of residual COVID viral components that lead to chronic inflammation, endothelial (lining of blood vessels) dysfunction or activation, reactivation of pre-existing chronic infections, microflora imbalances in the gut, and unrepaired tissue damage.

Here’s a closer look at a few of them.

  1. Viral Persistence

Viral persistence is characterized by ongoing shedding of SARS-CoV-2 after the acute infection has run its course. These persistent infections from long COVID shedding may fly under the radar, but their subclinical viral presence is thought to continuously aggravate the immune system – which, in turn, may trigger chronic inflammation.

Indeed, persistent COVID viral RNA was found in the feces of a group of individuals months after clearing the initial infection, according to one study reported by researchers at the Yale School of Medicine. These individuals also reported experiencing residual GI symptoms months after being diagnosed with COVID.

If long COVID develops due to subclinical levels of the virus persisting in the body, that would make the condition similar to other infection-associated chronic conditions (also called post-acute infection syndrome) such as CFS, Lyme disease, EBV, or herpes zoster (shingles) that develop after the acute infection has passed.

  1. COVID and Dormant Infections

Because COVID can cause immune system dysfunction, scientists sought to explore an important question: Can COVID reactivate infections? After all, a compromised long COVID immune response could leave an opportunity for previously dormant viral or bacterial infections to re-emerge—especially the IACC’s just mentioned.

There’s a likely connection between COVID and immune system reactivation, evidence suggests. EBV, which causes mononucleosis and other illnesses, appears to be reactivated in some long COVID patients. Indeed, research shows that an increase of EBV antibody levels are present in some individuals with continuing long COVID symptoms.

Additionally, research has found many overlaps between long COVID symptomatology with clinical presentation of chronic fatigue syndrome. Twenty-five out of 29 known chronic fatigue symptoms were noted in one COVID study. However, it is still not exactly clear how COVID impacts chronic illnesses.

  1. Autoimmunity

SARS-CoV-2 infection may trigger autoimmune disease. Some patients with long COVID have elevated levels of autoantibodies (malfunctioning immune cells), which are thought to play a role in autoimmune disorders such as rheumatoid arthritis, lupus, or Sjögren’s syndrome, Yale Medicine reports.

Antibodies help to protect against foreign invaders, such as bacteria and viruses. However, autoantibodies can attack the body’s own cells, leading to inflammation and tissue injury.

In some patients with long COVID, antinuclear autoantibodies have been observed up to one year after acute infection. They can target parts of cell nuclei, which may promote inflammation and damage organ systems.

For instance, in the inner lining of blood vessels (the endothelium), these antinuclear autoantibodies can create a hyper-inflammatory state or alterations to blood cells that can lead to inappropriate clotting.

  1. Inflammation

Inflammation, or recruiting white blood cells and the release of cytokines that initiate tissue swelling and injury, may also underlie some types of long COVID. The acute phase of COVID infection alters tissue function and unleashes a chronic inflammatory state in cells, specifically cells in the brain that are longer-lived. Inflammation is one of the major chronic illness triggers after COVID.

All of the theories noted above may possibly contribute to the sustained inflammation seen in long COVID cases.

WHAT IS LYME DISEASE?

Lyme disease is a bacterial infection that develops after a person is bit by a tick carrying the infection-causing bacterium, Borrelia burgdorferi. In rare cases, Lyme can develop from another tick-carrying bacterium called Borrelia mayonii.

While cases of Lyme have been reported in all 50 sates in the U.S., the vast majority of Lyme disease is found in the Northeast, mid-Atlantic, and upper-Midwest.

LYME DISEASE SYMPTOMS 

When Lyme disease infection first occurs, the most common symptom is an erythema migrans rash. It appears like a red circle with a bullseye on the skin. Research has found about 70-80% of cases have this rash, which appears at the site of the tick bite.

Over time, other symptoms of Lyme disease may appear. However, some people may not notice any symptoms initially. The CDC notes that any of the following early symptoms of Lyme disease typically appear three to 30 days after the tick bite:

  • EM rash
  • Headache
  • Fatigue
  • Fever
  • Chills
  • Muscle and joint aches
  • Swollen lymph nodes

Days or even months after the tick bit, these later symptoms may appear:

  • EM rashes that appear on other areas of the body
  • Severe headaches and neck stiffness
  • Arthritis (particularly in large joints like the knees)
  • Pain that comes and goes in the tendons, joints, muscles, and bones
  • Facial paralysis or severe weakness of facial muscles
  • Heart palpitations or an irregular heartbeat
  • Bouts of dizziness or shortness of breath
  • Shooting pain, tingling, or numbness in the feet and or hands
  • Nerve pain
  • Brain and spinal cord inflammation
  • Sometimes if an individual receives treatment right away, before the condition develops, they may not experience these later symptoms of Lyme disease.

Lyme disease may also trigger symptoms related to mental health conditions, such as:

  • Brain fog
  • Anxiety
  • Depression
  • OCD
  • Memory loss

And similar to long COVID, some Lyme patients continue to have ongoing symptoms, which can be severe and debilitating. The CDC calls this phenomenon post-treatment Lyme disease syndrome (PTLD), also known as chronic Lyme disease.

Many researchers and clinicians believe that the persistence of bacteria is the cause of these lingering symptoms. The antigen that triggers the inflammatory responses in chronic Lyme symptoms is found on the outer layer of the bacterial cell wall.

Pieces of these bacterial cell walls can linger in the body—undetected in the neurons or spinal cord, even post infection. This may contribute to the prolonged inflammation that leads to chronic illness.

According to a recent 2024 study in the Journal of Infectious Diseases, prevalence of PTLD varies from 0% to 48%, depending on how chronic Lyme disease is measured and defined. Some advocacy groups settle on a prevalence rate of 30%.

LONG COVID AND LYME DISEASE

COVID symptoms and Lyme disease share similar symptoms, but that’s not all. In a 2022 study, researchers found that chronic Lyme and COVID-19 are linked as having a history of Lyme disease correlated to increased risk of severe COVID-19.

In fact, long COVID and Lyme disease have so many overlapping similar features, research has been conducted to find biomarkers that differentiate between the two conditions.

Unfortunately, without clear biomarkers, the lack of differences between them impedes scientific research, according to some experts. A potential participant in a trial might be sick from long COVID, Lyme, or another infection-associated chronic condition.

At Amen Clinics, brain SPECT imaging and lab work play important roles in helping determine the underlying root cause of symptoms.

At this point, there are currently no FDA-approved treatments for chronic Lyme, or full-scale clinical therapy trials, which is very common among chronic conditions. But there’s hope that with the prevalence of long COVID, new research will reveal therapies that may help treat all of these similar chronic conditions, such as COVID, Lyme, EBV, CFS, and the herpes zoster.

MANAGING POST-COVID LYME SYMPTOMS

Until an effective treatment is found, post-COVID Lyme symptoms can be managed through lifestyle changes. (Of course, an acute Lyme infection requires antibiotics.) Here’s what you can do for chronic Lyme and long COVID symptoms:

  • Support from a qualified mental health professional, good sleep hygiene, consuming a brain healthy diet and avoiding alcohol, excess sugar, and refined carbohydrates can all help to support a healthy mood and keep inflammation levels down.
  • Additionally, practicing deep breathing or mindfulness practice like yoga, tai chi, or meditation can help keep anxiety levels down, and inflammatory cortisol levels in check.
  • Acupuncture, gentle massage, heat, stretching and toning exercises, and water therapy are all good for managing pain.

We're Here To Help

Lyme disease, long COVID, and other mental health conditions can’t wait. At Amen Clinics, we’re here for you. We offer in-clinic brain scanning and appointments, as well as mental telehealth, clinical evaluations, and therapy for adults, teens, children, and couples. Find out more by speaking to a specialist today at 888-288-9834 or visit our contact page here.

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Yale Medicine Website, https://www.yalemedicine.org/news/the-long-covid-puzzle-autoimmunity-inflammation-and-other-possible-causes. Accessed December 21, 2025

 

Snair M, Liao J, Ashby E, et al., editors. Toward a Common Research Agenda in Infection-Associated Chronic Illnesses: Proceedings of a Workshop. Washington (DC): National Academies Press (US); 2024 Apr 3. 2, Overview of Infection-Associated Chronic Illnesses.

 

 

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Yale Medicine Website, https://www.yalemedicine.org/news/the-long-covid-puzzle-autoimmunity-inflammation-and-other-possible-causes. Accessed December 20, 2025

 

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