‘Chronic Lyme’ Patients Are Getting Left Behind, but Long COVID Research Is Sparking New Hope

“If I took my dog on a 20-minute walk, I was in bed for the rest of the day,” she says. “Forget about going to the gym, despite the fact that I had been an athlete growing up.”

Then there were the cognitive issues—memory lapses, brain fog, confusion. “I couldn't remember my friends' names,” Adams says. “My best friend would say to me, ‘where do you want to go to dinner?’ And I had to have her repeat that to me five times before I understood the context of the question.”

An endocrinologist diagnosed Adams with Hashimoto's thyroiditis—an autoimmune disease that causes hypothyroidism—but treatments didn’t help.

Then her OB/GYN suggested a Lyme disease test. Standard testing recommended by the Centers for Disease Control and Prevention (CDC) came back negative, so her doctor—who had been diagnosed with Lyme disease herself—offered a different antibody test she said was more sensitive to picking up Lyme. Adams tested positive, and in 2005 her OB/GYN diagnosed her with late-stage Lyme disease and prescribed antibiotics.

Debilitating symptoms dragged on for months as Adams dealt with what’s now sometimes referred to as chronic Lyme (or long Lyme), a term that’s notoriously debated among experts. (The CDC uses the term post-treatment Lyme disease syndrome, or PTLDS, but experts don’t universally agree on that, either.)

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Michal Caspi Tal, PhD, a researcher at the Massachusetts Institute of Technology (MIT) who studies immune responses to tick-borne diseases with a specialization in Lyme, notes that many folks fail to meet the “extremely stringent” criteria many doctors use to diagnose PTLDS. But these patients often know something is wrong with their bodies, and many say they haven’t felt like themselves since their initial bout of illness.

Too often, these patients are getting left behind by the health care system. People with very real but hard-to-diagnose post-Lyme symptoms often end up seeing doctors who are “operating outside of insurance and outside of many of our established standards of care,” says Tal. For many folks who suspect they have lingering Lyme symptoms, “this is the only option,” she adds. “We have these big cracks in the medical system, and people are falling through.”

For decades, infection-associated chronic illnesses like chronic Lyme have been “woefully understudied,” says David Putrino, PhD, director of rehabilitation innovation for Mount Sinai in New York City and a professor in the Department of Rehabilitation and Human Performance, dedicated to long Lyme and other infection-associated chronic illnesses. The tide may be turning, though. “We are only just starting to see some really exciting work emerge now, because of the SARS-CoV-2 pandemic.”

In other words, one of the unexpected effects of COVID-19 has been a new breath of life for research around Lyme disease and chronic Lyme symptoms.

Here’s a deeper look at PTLDS, including the controversy around it, the treatments currently available, and why COVID may be the key that unlocks a more hopeful future for people managing the condition.

Here’s what we know about PTLDS

Lyme disease is an infection usually caused by the bacterium Borrelia burgdorferi and transmitted through the bite of an infected black-legged tick, according to the CDC. Lyme disease affects people in almost every state, although it's most commonly an issue in the Northeast, Northwest, and upper Midwest, per Johns Hopkins Medicine. When it’s caught early, Lyme can be cured in a majority of cases with a simple course of antibiotics. But a portion of people don’t feel better after this first-line treatment, per the National Institute of Allergy and Infectious Diseases (NIAID).

Lyme can also be tricky to detect sometimes. It’s unlikely you’ll feel it when a tick bites you: A tick’s saliva contains numbing agents that block pain and itch, so it’s easier for them to gorge on the blood of their hosts. And the symptoms of Lyme disease can creep in slowly, from three to 30 days after the tick feasts. The hallmark symptom is a rash that gradually expands from the site of the tick bite over several days. You might automatically think of a bullseye rash as the classic Lyme rash, but this only appears in about 1 in 5 cases. And about 20 to 30 percent of infected people never develop a rash at all.

If you’re bitten by a tick on a part of your body you can’t easily spot, like your back or behind your knees, you might not even notice this lesion if it develops, Tal notes. About 1 in 4 people only experience vague, flu-like symptoms—like fever, chills, headache, fatigue, muscle and joint pain, and swollen lymph nodes—that can easily be mistaken for other run-of-the-mill health issues. Less commonly, some folks have no symptoms at all.

If Lyme disease goes untreated, it can progress and attack the nervous system, heart, and joints, among other parts of the body, leading to more severe symptoms similar to those Adams experienced: headaches, memory issues, a stiff neck, facial muscle paralysis, numbness, tingling, heart palpitations, and joint swelling and pain.

Even with treatment, up to an estimated 10 percent of people with a confirmed Lyme infection will develop PTLDS. This means they experience symptoms—fatigue, body aches, difficulty thinking—that last after they complete the standard one-month antibiotic treatment, according to the CDC.

Tal contends that people with PTLDS or long Lyme report many more severe “new onset health problems” throughout their bodies. This includes brain fog with “even basic cognitive tasks;” dysautonomia (a disturbance of your autonomic nervous system, which controls blood pressure and other bodily functions and “can make it difficult to stand or possibly even sit upright for prolonged periods”); gastrointestinal distress; and “tremendous pain, sometimes in large, weight-bearing joints,” she says.

The chronic Lyme controversy

Researchers don’t fully understand what causes lingering symptoms after a Lyme infection. Some people may simply have an ineffective immune response, or the bacteria may trigger an “atypical” autoimmune response, Tal says.

And the bacteria that cause Lyme can be sneaky. In fact, Borrelia burgdorferi is thought to have defenses that help it “hide from the immune system,” as University of New Haven researchers put it, which might explain why antibiotics sometimes fail. (That said, the CDC doesn’t like the term “chronic Lyme,” because“it implies that prolonged symptoms are caused by an ongoing bacterial infection when, in fact, the cause is not currently known.”)

“Although adequate studies have not been done in people, if you speak to a veterinarian about whether or not tick pathogens persist, they will tell you absolutely. Yes. All the time they see it,” Putrino says.

Part of the chronic Lyme controversy may hinge on testing. The CDC recommends a two-step testing process for Lyme disease, which uses a blood sample to detect specific Lyme antibodies (protective proteins your body makes if an infection is present). You only need the second test (a Western blot) if the first test (ELISA) is positive or inconclusive. But this process isn’t perfect, and false positives and negatives are known to happen, the CDC notes. If you get tested too soon after a tick bite, for example, there’s a good chance you’ll end up with a false negative, because antibodies can take weeks to ramp up in your body.

Tal points out that a technique commonly used by immunologists, known as flow cytometry, has much higher sensitivity and resolution than the Western blot and ELISA tests. Instead of taking weeks to pinpoint antibodies, it can pick up on many more immune markers days after infection. (Other commercial tests already on the market, like the one used for Adams, look for a broader array of immune markers and use PCR and other more sensitive techniques, Tal notes, so they’re more likely to come back positive. But some doctors argue that the accuracy of these tests hasn’t been adequately studied.)

If you aren’t officially diagnosed with Lyme disease using the CDC-recommended tests, you don’t meet the criteria for PTLDS (that’s where chronic Lyme comes in). Tal adds that many clinics won’t accept the term “chronic Lyme” and won’t treat you for a Lyme infection—even if you’ve tested positive for it in the past—if it’s no longer considered to be acute.

Enter: issues with Lyme treatment. In the optimal “treatment window” for Lyme, or in the first three months of a confirmed infection, Tal says the disease can be effectively eradicated in 90 percent of people with the CDC-recommended protocol of two to four weeks of oral antibiotics, like doxycycline or amoxicillin. The caveat: “When you get beyond that [treatment window], antibiotics do become less effective,” Tal says. And because a timely and accurate Lyme diagnosis can be tricky to get—again, thanks to finicky tests and easy-to-miss symptoms, as well as socioeconomic barriers like lack of nearby doctors or insurance coverage—“many patients don’t even have the opportunity to access antibiotics,” she adds.

Limited treatment options for ongoing symptoms

Because the potential causes of PTLDS are murky (and chronic Lyme itself is debated), the treatment options are limited, too. The type of doctor you’ll see—say, an infectious disease specialist, cardiologist, neurologist, or rheumatologist—depends on the symptoms you’re coping with, says William Robinson, MD, PhD, chief of the Division of Immunology and Rheumatology at Stanford Health Care. They’ll likely want to run tests of their own, and you may need to experiment a bit with medications depending on how you’re progressing and feeling in your day-to-day life. If you do land a knowledgeable specialist, “there are many things that can be done to manage overall symptom burden,” says Putrino, pointing to vagus nerve stimulation, supplements, and emerging antibiotic protocols.

For five years, Adams took supplements and cycled through antibiotics. “I was feeling better, but I was still sick, and I had the symptoms to prove it,” she says. Antibiotics, of course, slaughter both bad and good bacteria, leading to side effects (such as recurrent yeast infections for Adams). Adams also had no way to know for sure whether her Lyme disease was cured: Current tests only look for Lyme antibodies, not the bacteria itself, so people continue to test positive for “months to years” after infection, even if the bacteria are gone, notes the CDC.

By 2010, though, Adams was able to go off antibiotics. “I've been able to sustain my remission. I'm really thankful for that,” she says.

The CDC and NIAID both recommend against extended antibiotic treatment, noting that it’s “no better than placebo” for addressing symptoms and is associated with potentially deadly complications like sepsis (an extreme response to infection) and colitis (inflammation of the colon). The CDC also says that patients with lasting symptoms “usually get better on their own,” given time.

“It’s hard to know what’s really going to help these individuals who are clearly ill,” Dr. Robinson says. “It’s an area where there are great unmet needs, and [the medical system] is struggling to serve these patients…These post-infectious syndromes are complex, and they frequently don’t map on to diseases for which we have randomized clinical trials and an FDA-approved drug.”

The hopeful news: Post-treatment Lyme research has gained momentum, thanks to the COVID-19 pandemic 

Like long Lyme, long COVID is associated with infection, and the two share many of the same symptoms. Because long COVID affects nearly 7 percent of the U.S. population, according to the CDC, it’s getting a lot more attention and funding than chronic Lyme. But the CDC says it’s working with health care providers and patients to “develop a common research agenda” for people with infection-associated chronic illnesses, including those with prolonged Lyme symptoms. What's more, Mount Sinai, Yale, and MIT now research and treat chronic Lyme alongside long COVID.

Scientists have also made progress on a number of new Lyme disease vaccines. And experts say new diagnostics and treatments are now within reach.

Tal’s group at MIT is researching immune markers to predict who will develop chronic symptoms after a Lyme infection (and who won’t). They hope this will help improve the design of future clinical trials for chronic Lyme treatments and help people access these treatments earlier in their illness, before symptoms become severe.

She’s also looking into sex differences in immunity. “Most of these significantly underfunded diseases are female-skewed,” Tal says, pointing to both long COVID and long Lyme as examples. “[Women] are 51 percent of the population. We can't just disregard diseases that primarily affect women. And so I really feel like there's a change in tide starting,” as a sort of ripple effect from the COVID pandemic. “Long COVID is getting these other diseases a lot of desperately needed recognition.”

Adams, 56, is the research grant director for the Bay Area Lyme Foundation, a nonprofit that gives early seed funding to institutions like MIT and Harvard to develop improved Lyme tests as well as treatments for later-stage patients. This includes a project on targeted therapeutics (similar to targeted drugs in cancer, but for a specific protein in Borrelia) at Duke, which just received funding from the Department of Defense. Unlike broad-spectrum antibiotics, which kill many good bacteria in their path, Duke’s drug aims to be more selective, which may also avoid contributing to antibiotic resistance.

“I think that this is a really incredible moment in time,” Tal says, noting that “major changes” are on the horizon.

“I'm extremely hopeful for the chronic Lyme community,” says Putrino. “I think that in the next few years, we're going to see some very important clinical trials in the field of chronic Lyme disease.”

—reviewed by Jennifer Logan, MD, MPH