Making Invisible Illnesses Visible: Recognizing and Responding to Infection Associated Chronic Conditions 2026 Iskander and Haridopolos

[Andy]

Abstract​

The emergence of post-COVID conditions (PCC) has renewed attention to infection-associated chronic conditions and illnesses (IACCI), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Lyme disease–associated chronic symptoms. Millions of Americans are affected by these debilitating, misunderstood conditions, which share symptom profiles and pathophysiologic abnormalities. IACCI have received insufficient clinical attention and research investment.

We outline elements of a patient-centered approach to care, emphasizing validation of patients’ experiences, multidisciplinary management, and symptom-focused treatment. Opportunities to strengthen clinical practice include a new CMS code for chronic condition management, extended visits, and creation of welcoming care environments. Advances in PCC and ME/CFS research provide a foundation for exploring shared mechanisms and developing targeted therapies. Improved surveillance, harmonized research, and inclusive trial designs are needed to define disease burden and accelerate therapeutic progress. Coordinated action by clinicians, researchers, and policymakers can help address longstanding gaps and improve outcomes for all individuals with IACCI.

Paywall

 

[Andy]

"patient-centered approach to care, emphasizing validation of patients’ experiences"

and of course nothing emphasises centering patients as much as your publication being behind a paywall meaning that the vast majority of them can't read it.... /s

 

[Nightsong]

Since this seems potentially important from a U.S. policy perspective, a few brief quotes -

Many patients with IACCI have faced longstanding skepticism about the very existence of what some have called “invisible illnesses”.4 Patients with diagnosed or suspected myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long expressed concerns that their health status was not accorded sufficient clinical and policy scrutiny. ME/CFS likely represents a post-infectious response triggered by various pathogens. The U.S. burden of ME/CFS is important from health and economic perspectives, with approximately 2.5 million affected individuals and up to $24 billion annually in total costs

Actions clinicians can take immediately include acknowledging to their patients the realities of these illnesses which defy simple medical explanation and the severe effect they have on day-to-day functioning. Because of the lack of Food and Drug Administration approved treatments for any of these conditions, a focus on treating symptoms, preventing IACCI when possible,14 and improving quality-of-life15 must exist concurrently with the knowledge-building progress of evidence-based medicine.

Chronic pain, a symptom commonly seen across all forms of IACCI, should be recognized and managed according to professional guidelines.16,17 Beyond focusing on symptom relief, important principles of care for persons with IACCI include creating a welcoming practice environment for individuals who have experienced longstanding frustration with the healthcare system, engaging a multidisciplinary care team, and enabling patients to find and use reliable information and avoid potentially harmful interventions

Whenever feasible, longer appointments with such patients, especially ones new to the practice, should be scheduled. Such scheduling allows time for a complete medical history and physical examination but also conveys that patients with IACCI are welcome. Clinical providers should guard against unintentionally stigmatizing or marginalizing patients who have symptoms, but do not yet have a clearly definable disease process.

Long COVID and ME/CFS prevalence estimates indicate that over 20 million persons in the U.S. are affected by the physical and mental struggles intrinsic to IACCI. It is likely that this figure is underestimated due to underreporting and recall bias. This documented disease burden is sufficient justification for ongoing investment in clinical quality improvement, therapeutics focused research, public health surveillance, and the creation and dissemination of evidence-informed treatment guidelines.22 Even for patients who have not yet received a specific diagnosis, cross-cutting “living” clinical guidelines for IACCI are now available.23 A selection of evidence-informed guidelines are featured in Box 2.

There are other specific recommendations, such as using a specific CMS diagnostic code (G2211) for "IACCI" patients. It also touches on the lack of evidence for antibiotic therapy in post-acute Lyme and recommends a search for causes other than persistent infection.

 

[Jonathan Edwards]

It all sounds very sensible but does it actually provide any useful guidance. There is still a talk of multidisciplinary care - without any reason being given. It would be nice to have therapies but what is 'therapeutics-focused research'? In my experience it is doing the biology first so that you have some chance of knowing where to look. When there are therapies with evidence, they will get used. Guidelines and their dissemination will follow for those that want them.

 

[rvallee]

emphasizing validation of patients’ experiences

Is any of this language found in illnesses that aren't disbelieved? Because I don't need someone to validate my experience, I need someone to understand it and do something smart and useful about it. I could not care less about validation, whatever it means to different people. It just needs to be treated normally, not separate from the rest of medicine.

Beyond focusing on symptom relief, important principles of care for persons with IACCI include creating a welcoming practice environment for individuals who have experienced longstanding frustration with the healthcare system, engaging a multidisciplinary care team, and enabling patients to find and use reliable information and avoid potentially harmful interventions

Like the above. This simply describes normal health care that works, based on science, as opposed to weird alternative medicine, biopsychosocial, not-care that doesn't work. Just do health care normally and stop being weird about it. I don't want smiling greeters at the door, I want competent physicians and nurses who know what they're doing because they understand the problem, with science. All of which requires throwing out the whole damn psychosomatic house of cards, with extreme prejudice.

I am not aware of any "symptom-focused treatment", in fact I don't really understand what it even means.

So many guidelines. I don't think any of them are any useful. This needs normalization and research, the rest is pointless.

 

[nataliezzz]

Why do we accept ME/CFS being classified as an "infection-associated chronic condition" when something like 40% of us had non-infectious onsets (with a large % of those having clear non-infectious triggers)?

 

[Andy]

In the DecodeME cohort of more than 16.5k, 62% of participants indicated an infectious trigger, only 16% identified a non-infectious onset trigger, and 22% indicated that they didn't know what triggered their ME/CFS, so while I don't think these infection-associated chronic condition 'buckets' are particularly useful, I do think that viewing ME/CFS as infection-associated is the most sensible path to follow.

 

[Sean]

Because I don't need someone to validate my experience, I need someone to understand it and do something smart and useful about it.

Or admit they got nothing useful to offer, at this stage, beyond diagnosis and generic support and medical care.

Why do we accept ME/CFS being classified as an "infection-associated chronic condition" when something like 40% of us had non-infectious onsets (with a large % of those having clear non-infectious triggers)?

This is one of those issues where we simply don't have a good handle on it. It is quite possible all cases are infectious onset, but in some cases the initial infection is very subtle or even entirely asymptomatic, so the patient has no reason to associate onset with an infection.

I am agnostic about this. Like so much about ME/CFS, at this stage we just don't know.

 

[duncan]

. It also touches on the lack of evidence for antibiotic therapy in post-acute Lyme and recommends a search for causes other than persistent infection

Eye roll.

When politics intrude into medicine, it's fairly safe to assume progress suffers.

I cannot speak to EBV or HHV6 or enteroviruses or whatever, although I'd wager research into each, at least diagnostically, has its own embedded hurdles.

But I can address tick-borne diseases. Here the question of persistence is thriving. The reason is simple: There have been many, many studies in all sorts of animals - dogs, monkeys etc - where persistence after abx has been undeniably demonstrated. Why not in humans? Well, it has been there as well, but since autopsies, targeted autopsies, need to be involved, that has been devilishly challenging. Cruelty aside, that is not the case with macaques and beagles.

Moreover, we are not merely looking at blood/serum. Testing for persistence (by virtue of the bugs involved) is usually constrained to tissue, very often brain tissue.

Even then, finding these agents is very hard to do. It can be hit or miss.

As for a lack of evidence for abx in post-acute Lyme, this also gets complicated very quickly, but an obvious point of contention is abx therapy duration, where the schism in belief is massive.

So, persistence remains very much on the table.