Long COVID or Lyme Disease? Key Differences

Shared symptoms can make diagnosis difficult
A careful evaluation helps distinguish the two
Treatment depends on the correct diagnosis

In the wake of the pandemic, we’ve become more aware of how a viral infection can lead to long-term, multisystem illness. That has been an important step forward. Patients with brain fog, fatigue, and shortness of breath are no longer automatically dismissed. They’re told it might be Long COVID—and for many, that’s exactly what it is.

But not every illness that appears post-viral is necessarily caused by a previous viral infection. And not every patient labeled with Long COVID has received the full explanation for their symptoms.

In my practice, I’ve seen patients whose fatigue, headaches, lightheadedness, poor sleep, and word-finding difficulties were immediately attributed to Long COVID. Some had never tested positive for COVID-19. Others had recovered from COVID without difficulty, only to become chronically ill months—or even years—later.

In a number of those cases, the symptoms were ultimately explained by Lyme disease or another tick-borne infection, such as Babesia or Bartonella. Yet tick-borne illnesses had never been included in the differential diagnosis.

What My Research Found About Long COVID and Lyme Disease

In 2023, my colleague and I published a peer-reviewed cross-sectional survey in the journal Antibiotics. The survey included 889 individuals with a history of Lyme disease, including groups who had contracted COVID-19, received a COVID-19 vaccine, or neither.

The findings raised an important clinical question: could a history of Lyme disease be associated with persistent symptoms after COVID-19?

Nearly one in five participants with a history of Lyme disease who contracted COVID-19 reported Long COVID. This finding raises an important question for future research, but the survey was not designed to establish increased risk or causation.

Participants reporting Long COVID also described a greater neurological symptom burden than participants who contracted COVID-19 but did not report Long COVID. Symptoms affected multiple domains, including fatigue, pain, neurological symptoms, and neuropsychiatric complaints.

When Diagnostic Labels Limit the Evaluation

Long COVID is an important diagnosis for many patients. However, in some situations, it can become the endpoint of the diagnostic evaluation before other possible explanations have been adequately considered.

When persistent symptoms are automatically attributed to COVID-19, clinicians may never ask about:

1. Possible tick exposure
2. Unexplained or unusual rashes
3. Travel, geographic, or seasonal patterns
4. Prior flu-like illnesses that were never diagnosed
5. Tick-borne co-infections that require different evaluation and treatment

I’ve seen patients treated for months as though they had Long COVID when the missing diagnosis was an untreated tick-borne illness.

A careful evaluation should consider the timing of symptoms, the patient’s exposure history, previous infections, physical findings, and other conditions that can produce a similar multisystem illness.

How Lyme Disease Can Mimic Long COVID

The overlap between Lyme disease symptoms and Long COVID can be striking. Both conditions may be associated with:

1. Persistent or severe fatigue
2. Autonomic dysfunction, including POTS
3. Brain fog and cognitive impairment
4. Exercise intolerance or post-exertional symptom flares
5. Sleep disturbance
6. Mood changes
7. Migratory muscle or joint pain
8. Gastrointestinal complaints
9. Neurologic symptoms

No single symptom reliably distinguishes Lyme disease from Long COVID. The pattern of illness, exposure history, onset of symptoms, physical findings, and response to previous treatment may all provide important clues.

For example, a history of outdoor exposure, an unexplained rash, facial weakness, migratory pain, new joint swelling, or symptoms that began during tick season may increase concern for Lyme disease or another tick-borne infection.

Symptoms such as air hunger, night sweats, chills, or unexplained anemia may also lead clinicians to consider Babesia, particularly in patients who live in or have traveled to an endemic region.

Long COVID and Lyme Disease Require Different Approaches

So what distinguishes Long COVID from Lyme disease?

The diagnosis—and ultimately the treatment.

Although the two illnesses may produce similar symptoms, their underlying mechanisms and treatment approaches are not the same. Identifying the most likely explanation for a patient’s illness is therefore essential.

Long COVID treatment generally focuses on symptom management, rehabilitation, treatment of associated conditions, and careful pacing when post-exertional worsening is present.

Lyme disease and certain tick-borne co-infections may respond to appropriate antimicrobial treatment when they are correctly identified. However, treatment decisions should be individualized according to the patient’s clinical presentation, diagnostic findings, previous treatment, and response over time.

It is also possible for a patient to have more than one condition. A previous COVID-19 infection does not prevent someone from later acquiring Lyme disease, Babesia, anaplasmosis, or another tick-borne infection.

The Cost of Diagnostic Delay

I’ve cared for patients who spent a year or more under the Long COVID umbrella before someone finally asked an important question:

Could this be Lyme disease?

By then, their symptoms had progressed. Their trust had eroded. And many had begun to lose hope.

Because Lyme disease testing has recognized limitations, diagnosis often depends on combining laboratory findings with the patient’s exposure history, symptoms, physical examination, and clinical judgment.

A negative test—particularly early in the illness—does not always exclude Lyme disease. At the same time, symptoms alone are not enough to confirm the diagnosis. Testing results must be interpreted within the complete clinical picture.

When we performed a more thorough evaluation and, in appropriate cases, began treatment for Lyme disease or Babesia, some patients gradually began to improve. Recovery was rarely immediate or linear, but meaningful progress became possible.

We Owe Patients More Than Assumptions

The recognition of Long COVID has advanced important conversations about chronic illness. But clinicians should be careful not to let the diagnosis become the end of the diagnostic journey when the clinical picture does not fully fit.

If a patient has persistent symptoms attributed to Long COVID but never tested positive, developed symptoms long after recovering from a mild infection, or continues to worsen despite supportive care, it is reasonable to ask:

1. Was Lyme disease adequately evaluated?
2. Were tick-borne co-infections considered?
3. Could another diagnosis better explain the clinical picture?

Sometimes the answer isn’t a new virus.

It may be an older infection that has gone unrecognized and is still waiting to be appropriately diagnosed and treated.

The goal is not to force every symptom into one label. The goal is to understand the full clinical picture.

Frequently Asked Questions

Can Lyme disease be mistaken for Long COVID?

Yes. Lyme disease and Long COVID can share symptoms including fatigue, brain fog, dizziness, autonomic dysfunction, exercise intolerance, sleep disturbance, and cognitive difficulties. Because these conditions overlap clinically, a careful history, physical examination, and appropriate diagnostic evaluation are important.

How do doctors distinguish Lyme disease from Long COVID?

Diagnosis depends on the patient’s history, possible tick exposure, symptom pattern, physical findings, and laboratory testing when appropriate. Because Lyme disease tests have recognized limitations, results should always be interpreted within the overall clinical context.

Can someone have both Lyme disease and Long COVID?

Yes. A person who has recovered from COVID-19 can later acquire Lyme disease after a tick bite, and it is also possible for both conditions to coexist. Persistent symptoms should not automatically be attributed to only one diagnosis.

Does a history of Lyme disease increase the risk of Long COVID?

That has not been established. In a cross-sectional survey, nearly one in five participants with a history of Lyme disease who contracted COVID-19 reported Long COVID. Additional controlled research is needed to determine whether Lyme disease history affects the risk of developing persistent symptoms.

Clinical Takeaway

Long COVID and Lyme disease are distinct conditions that can produce remarkably similar symptoms. Fatigue, brain fog, dizziness, autonomic dysfunction, sleep disturbance, and exercise intolerance occur in both illnesses, making diagnosis challenging.

A thorough differential diagnosis remains essential. Careful attention to exposure history, timing of symptoms, physical findings, and appropriate laboratory testing can help identify patients whose illness may represent Lyme disease or another tick-borne infection rather than Long COVID alone.

Patients deserve a careful evaluation that keeps an open mind and considers all clinically reasonable possibilities before a diagnosis is finalized.

Related Articles

POTS and Lyme disease
Lyme disease misdiagnosis
Persistent Lyme disease overview
Recovery from Lyme disease

References

1. National Academies of Sciences, Engineering, and Medicine. Long-Term Health Effects of COVID-19: Disability and Function. National Academies Press; 2024.
2. Centers for Disease Control and Prevention. Long COVID. Accessed 2026.
3. Centers for Disease Control and Prevention. Clinical Care of Lyme Disease. Accessed 2026.
4. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014;12(9):1103–1135.
5. Cameron DJ, McWhinney SR. Consequences of contracting COVID-19 or taking the COVID-19 vaccine for individuals with a history of Lyme disease. Antibiotics. 2023;12(3):493.

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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