Lyme or Long COVID? How to Tell the Difference
Quick Answer: Lyme disease and Long COVID can cause nearly identical symptoms—including brain fog, fatigue, and joint pain—making diagnosis difficult. Treatment response and clinical history often provide the best clues.
Clinical Insight: When symptoms overlap this closely, the challenge is not just identifying the illness—but recognizing that more than one process may be contributing.
Three years after recovering from Lyme disease, Jennifer developed COVID-19. Months later, the same crushing fatigue, brain fog, and joint pain returned.
Was it Long COVID—or Lyme again?
This scenario is increasingly common—and often confusing for both patients and clinicians.
Why Lyme and Long COVID Feel So Similar
Lyme disease and Long COVID share a cluster of symptoms that can be difficult to distinguish.
Both conditions can cause:
- Brain fog that won’t lift — Losing words mid-sentence or struggling with familiar tasks. Learn more about brain fog in Lyme disease.
- Exhaustion that sleep doesn’t fix
- Heart symptoms — Racing, skipping, or pounding unexpectedly
- Migrating pain — Joint and muscle pain that moves
- Post-exertional crashes — Activity leading to days of fatigue
This overlap is a major reason patients are often misdiagnosed.
What Causes the Overlap?
Both conditions appear to involve:
- Immune system dysregulation
- Chronic inflammation
- Nervous system involvement
- Autonomic dysfunction
Learn more about autonomic dysfunction.
Even though Lyme disease is caused by bacteria and Long COVID follows a viral infection, the body’s prolonged response can produce similar symptoms.
The key difference: Lyme disease may involve an ongoing infection, while Long COVID reflects a lingering immune response.
How Treatment Can Help Tell the Difference
Treatment response can offer important clues.
If it’s Lyme disease, patients may:
- Improve with antibiotics (if infection is active)
- Respond to treatment for co-infections such as Babesia
- Benefit from anti-inflammatory strategies
If it’s Long COVID, patients may:
- Require pacing to avoid crashes
- Benefit from rehabilitation (cardiac, pulmonary, cognitive)
- Respond to therapies targeting inflammation or nervous system regulation
However, recovery does not always follow a clear pattern.
When Patients Have Both
Some patients with a history of Lyme disease develop new symptoms after COVID infection.
Others report that their previous Lyme symptoms return or worsen.
This raises important questions:
- Has Lyme disease reactivated?
- Is Long COVID driving symptoms?
- Are both conditions contributing?
This overlap makes diagnosis and treatment more complex.
Managing Overlapping Symptoms
Instead of focusing only on labels, treatment can focus on shared mechanisms:
- Reducing inflammation
- Supporting cellular energy
- Addressing autonomic dysfunction
- Improving brain function and clarity
This approach can help patients improve regardless of the underlying diagnosis.
Clinical Takeaway
Lyme disease and Long COVID can look nearly identical—but the underlying causes and treatments may differ.
In some cases, both conditions may be present.
Careful evaluation—and sometimes trial of treatment—may be necessary to determine the best approach.
Frequently Asked Questions
Can you have both Lyme disease and Long COVID?
Yes. Some patients develop Long COVID after a prior Lyme infection, and symptoms may overlap or worsen.
How do I know which condition I have?
It can be difficult to distinguish. Treatment response and clinical history often provide the best clues.
Can COVID reactivate Lyme disease?
Some patients report recurrence of Lyme-like symptoms after COVID. Research is ongoing, but immune changes may play a role.
What should I do if symptoms overlap?
Focus on shared treatment strategies and work with a clinician familiar with post-infectious illness.
Bottom Line
When symptoms overlap this much, the label matters less than finding what helps you recover.
Working with a clinician who understands both conditions can make a critical difference.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
I was previously treated for a co-infection of Babesia Ducani and Bergerdorfer. Unfortunately, I wasn’t treated for over a decade after chasing down symptoms and misdiagnosis. Even though my initial infection included three bullseye rashes, 105 fever for 10 days, I could barely walk, and had insane headaches, and pain. I was told it was just a virus.
I never truly recovered and spent the next 10+ years in poor health and eventually developed Hashimoto’s, then thyroid cancer, my gallbladder shriveled up and I developed Lipodema.
I had a 4 years period where Lyme went into remission and I felt amazing and back to myself. I have never been able to figure out what changed other than the removed my gallbladder. Unfortunately, the symptoms returned during a period of stress.
Now, I have been diagnosed with Long-Covid and the 200 symptoms and conditions that come with including a re-activation of Epstein-Barr. They have run Lyme tests and did a spinal tape amd nothing came back positive, but I fear they still haven’t ordered the proper tests. When I was originally diagnosed it was after an antibiotic challenge test and they found dead spiroquettes in my blood. I want to do that test again but I can’t remember (imagine that) where It was performed. Do you know how I can get that test? Two of my doctors want me to get an IVIG so we are working with insurance to get it. What do you think about that?
I wish the tests were more reliable. For example, only 2 of 27 patients with chronic neurologic Lyme had a positive test by spinal