In our previous article, we set out the numbers: over 700,000 new Lyme disease cases globally each year, a Long Lyme population growing by tens of thousands annually, and a diagnostic market built on tests that miss up to 60% of early infections. Numbers, though, tell only part of the story. Behind each one is a person, often exhausted, often in pain, and very often disbelieved.
This article is about what those patients go through, why the system fails them, and what we at Attomarker believe can be done about it.
A Test That Fails When It Matters Most
The standard diagnostic pathway for Lyme disease, two-tier serological testing, relies on the patient’s immune system generating a detectable antibody response to Borrelia antigens. The problem is one of timing. In early localised disease, when the infection is most treatable and the clinical window most critical, two-tier serology has a sensitivity as low as 30–40% [1]. The test is most likely to return a negative result precisely when a positive one would do the most good.
Patients who present with the characteristic erythema migrans rash can be diagnosed clinically, but up to 20–30% of Lyme disease patients never develop a recognisable rash [2]. For these individuals, a negative serology result may be the only data point a clinician has, and it is, statistically, more likely to be wrong than right.
The consequences ripple outward. A missed early diagnosis means delayed or absent treatment. Delayed treatment increases the risk of disseminated disease (cardiac, neurological, arthritic) and raises the probability of progression to Long Lyme. A diagnostic failure in week two becomes a clinical burden that lasts years.
The Long Lyme Odyssey
For the estimated 10–20% of patients who develop persistent symptoms after treatment, the diagnostic picture does not improve; it collapses entirely. There is no validated laboratory test for Long Lyme. No biomarker. No objective measure that a clinician can point to and say: this is what is wrong.
The resulting patient experience is one that will be painfully familiar to anyone who has followed the Long Covid story. A 2017 study characterising a well-defined PTLDS cohort documented what patients themselves have described for decades: a relapsing, fluctuating course of fatigue, pain, and cognitive impairment that resists simple categorisation [3]. More recent work has shown that Long Lyme patients report an average diagnostic delay exceeding two years, with many consulting five or more clinicians before receiving a diagnosis, if they receive one at all [4].
During that time, patients describe a recurring pattern: symptoms are acknowledged but attributed to stress, depression, ageing, or somatisation. Test results come back normal, because the tests being ordered are not designed to detect what is wrong. Referrals loop between rheumatology, neurology, psychiatry, and general practice without resolution. The phrase patients hear most often is some variant of “there’s nothing wrong with you.”
The psychological toll is substantial. Depression, anxiety, loss of employment, relationship breakdown, and social isolation are widely reported in Long Lyme cohorts [5]. These are not the causes of the condition; they are its consequences, compounded by a medical system that lacks the tools to see what patients are living through.
A Medical Community Divided
The patient struggle is made worse by a deep and long-standing division within the medical profession itself. The Infectious Diseases Society of America (IDSA) has historically attributed persistent post-treatment symptoms to immune dysregulation rather than ongoing infection, recommending against extended antibiotic therapy [6]. The International Lyme and Associated Diseases Society (ILADS), by contrast, has argued for the possibility of persistent Borrelia infection and advocated more flexible treatment approaches [7].
This is not merely an academic disagreement. It determines whether patients are believed, whether they are treated, and whether their condition is recognised by insurers, employers, and disability assessors. Patients caught between these positions often find themselves navigating not just a medical challenge but a political one, forced to advocate for their own legitimacy in a system that cannot agree on whether their illness exists in the form they experience it.
The Long Covid Parallel, and What It Taught Us
The emergence of Long Covid following the SARS-CoV-2 pandemic brought post-infectious chronic illness into the mainstream in a way that decades of Lyme disease advocacy had not managed to achieve. The parallels are striking: overlapping symptom profiles (fatigue, cognitive impairment, autonomic dysfunction, pain), a similar absence of definitive biomarkers, and a similar pattern of patient dismissal in the early stages [8].
At Attomarker, Long Covid was the catalyst that proved a principle. Using our rapid multiplex serology platform, we demonstrated that patients with persistent post-Covid symptoms frequently exhibit distinctive immunological signatures, including altered antibody titres, class-switching patterns, and evidence of immune dysregulation, that differ measurably from those who recover fully [9]. Crucially, these are not single-analyte findings. They are multi-dimensional immune profiles that only become visible when you measure many things at once, from a single sample, and look at the pattern.
This is the insight we believe can transform Lyme disease diagnostics.
Our Hope: Multiplex Serology for Lyme and Long Lyme
The limitations of current Lyme disease testing are not inevitable; they are artefacts of a diagnostic paradigm built around single-target, sequential serology. At Attomarker, we take a fundamentally different approach: simultaneous measurement of antibody responses to a broad panel of antigens from a single small-volume blood sample, with results delivered in minutes.
Applied to Lyme disease and Long Lyme, this approach opens four critical doors.
Improved sensitivity in early disease. A multiplex panel spanning conserved and species-specific Borrelia antigens, across the genospecies diversity relevant in Europe and beyond, can capture immune responses that single-target EIAs miss. Measuring IgM and IgG simultaneously across multiple targets increases the probability of detecting early seroconversion, narrowing the diagnostic window that currently lets so many patients fall through.
Objective biomarkers for Long Lyme. By incorporating both pathogen-specific and host-immune markers, including autoantibody targets implicated in post-infectious autoimmunity, a multiplex panel can provide the quantitative, objective evidence that Long Lyme patients so desperately need. Identifying immunological subgroups within the Long Lyme population would not only validate lived experience but inform treatment stratification: distinguishing patients with ongoing immune activation from those with autoimmune features or resolved infection with residual symptomatology.
Differential diagnosis in a single test. Many Long Lyme symptoms overlap with tick-borne co-infections (Anaplasma, Babesia, Bartonella) as well as autoimmune and other post-infectious conditions. A multiplex approach allows clinicians to test broadly from a single sample, replacing months of sequential investigation with a single, comprehensive diagnostic moment.
Tracking change over time. Repeat multiplex profiling can monitor immune responses longitudinally, assessing treatment response, identifying relapse, and informing prognosis. This moves Lyme disease management away from a binary positive-or-negative model toward the kind of data-rich, individualised care that patients deserve.
A Commitment
We have seen in Long Covid what diagnostic failure does to patients: it isolates them, impoverishes them, and erodes their trust in a system that is supposed to help. The Long Lyme community has endured this for far longer, with far less public recognition.
We cannot fix the decades of dismissal that have already occurred. But we can build the tools to ensure that the next patient, presenting with fatigue, pain, and cognitive fog after a tick bite they may not even remember, gets an answer that is fast, accurate, and clinically meaningful.
That is our commitment, and it is the same commitment that drives everything we do at Attomarker: better answers, sooner, for the patients who need them most.
This is the second in a two-part series on Lyme disease and Long Lyme. Read the first article, The Scale of Lyme Disease and Long Lyme: A Global Burden in Numbers, for a full epidemiological and market overview.
References
[1] Wormser GP et al. “Clinical practice guidelines by the IDSA.” Clin Infect Dis. 2006;43(9):1089–1134.
[2] Steere AC et al. “Prospective study of serologic tests for Lyme disease.” Clin Infect Dis. 2008;47(2):188–195.
[3] Rebman AW et al. “The clinical, symptom, and quality-of-life characterization of a well-defined group of patients with post-treatment Lyme disease syndrome.” Front Med. 2017;4:224.
[4] Rebman AW, Aucott JN. “Post-treatment Lyme disease as a model for persistent symptoms in Lyme disease.” Front Med. 2020;7:57.
[5] Johnson L et al. “Severity of chronic Lyme disease compared to other chronic conditions: a quality of life survey.” PeerJ. 2014;2:e322.
[6] Wormser GP et al. (IDSA Guidelines). Clin Infect Dis. 2006;43(9):1089–1134.
[7] Cameron DJ et al. “Evidence assessments and guideline recommendations in Lyme disease.” Expert Rev Anti Infect Ther. 2014;12(9):1103–1135.
[8] Komaroff AL, Bateman L. “Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome?” Front Med. 2021;7:606824.[9] Cervia C et al. “Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.” Nat Commun. 2022;13:446.