Key Point 

• Postacute infection syndrome has been poorly understood, but it is being studied. Clients with these problems may seek out massage therapy because the conventional medical community has little to offer them.

A person goes through a bout of COVID. They survive, but weeks or months later, they develop mysterious symptoms they’ve never had: postural orthostatic tachycardia syndrome (POTS), dizziness and vertigo, or debilitating fatigue and mental fogginess. These symptoms may last months or longer. What is happening?

Another person has mononucleosis or some other common viral infection, and after a long recuperation, they expect to be back at full pre-infection speed. Only they can’t. Their body doesn’t have the capacity to work at a job for eight hours, plus cook meals, go grocery shopping, clean the house, do laundry, and participate in family life. They live in exhaustion, plagued by fatigue and general pain. Their invisible disease isn’t life-threatening, but it is definitely quality-of-life threatening.   

We’ve all heard about long COVID, and chronic fatigue syndrome (CFS) is probably on our radar already. Here, we will look at postinfectious problems as a whole to see what they have in common and if what we currently understand about them gives any clues about the best role for massage therapy. 

What is PAIS?

Until recently, the acronym PAIS was most commonly associated with a condition called partial androgen insensitivity syndrome—not the topic of this article. Now, PAIS also stands for postacute infection syndrome, a group of signs and symptoms that follow viral, bacterial, or parasitic infections. PAIS is a health challenge that follows a short-term infection, but the consequences of that infection may linger for months or longer. Long COVID is the PAIS that is most researched now, but this spectrum of postinfection problems has been documented since the 1918 flu pandemic.   

A recently published large-scale review looking at PAIS is getting the attention of many medical professionals, and a newly launched program—the Center for Infection and Immunity, within the Department of Immunology at Yale—won a substantial grant to study PAIS, so the discussion of these problems has entered mainstream medicine in ways we haven’t seen before.  

The hope is this attention will help us recognize the causes of PAIS and prevent or cure them. It’s a daunting task: Evidence of microbiome disruption, mitochondrial dysfunction, microscopic blood clotting, permanent tissue damage, and much more have been found to be possible contributors. But the consistent overlap of several key signs and symptoms has led researchers to propose there may be a common pathophysiology that links these problems.

Core PAIS Symptoms

Every person who has a persistent postinfection issue is likely to have a unique experience, but observers have collected a group of signs and symptoms that appear consistently in many versions of this situation. These include exertion intolerance, disproportionate fatigue, neurocognitive disruption (“brain fog”), dysautonomia, sensory impairment, flu-like symptoms (fever, malaise, nausea, sweating), cough, shortness of breath, weakness, unrefreshing sleep, and muscle and joint pain. You may recognize that this list can describe many situations, including fibromyalgia, hypothyroidism, and incompletely treated diabetes, but those conditions are not (yet) associated with a pre-occurring infection. 

Examples of PAIS

Both CFS and long COVID—the most widely acknowledged forms of PAIS—are recognized by their symptomatic profile rather than by a specific pathophysiology. This points out how subjective the identification of these problems can be, and how difficult it is to create a consistent and accurate set of diagnostic criteria. Following are a few examples of PAIS. I’ve chosen most of these because massage therapists are likely to have clients who live with these conditions. 

Long COVID

Also called postacute sequelae of COVID (PASC), long COVID is a driver for much of the current research into PAIS. The specific definition of long COVID is still under debate, with the World Health Organization, the Centers for Disease Control and Prevention, and others having their own ideas about severity, duration of symptoms, and possible contributing factors. While many people with long COVID have the core signs and symptoms of all PAIS conditions, the persistent loss of the senses of smell and taste (anosmia and ageusia) that many patients experience is unique to this condition.

ME/CFS

This condition, called CFS in the US and Canada, and myalgic encephalomyelitis (ME) in many other places, is now often referred to as ME/CFS. Historically, this collection of signs and symptoms has been associated with a prolonged recovery from infection with Epstein-Barr virus (EBV), the causative agent of mononucleosis. That is an oversimplification, and many people who meet the diagnostic criteria for ME/CFS have no signs of EBV infection. Furthermore, it has been shown that exposure to several other pathogens can result in diagnostically identical signs and symptoms. ME/CFS is recognized as the cornerstone of PAIS, and some experts now consider that what begins as long COVID may eventually evolve into ME/CFS.

Chronic Lyme, Posttreatment Lyme Disease Syndrome

Some people who contract the bacterial infection called Lyme disease develop long-term symptoms that range from being mildly discomforting to being completely debilitating. These include the core PAIS symptoms, but people with chronic Lyme may also report alarming experiences with peripheral neuropathy, arrhythmia, and more. This topic is explored in the July/August 2022 issue of Massage & Bodywork magazine, in the article “Long-Term Lyme Disease” (page 72).

Postpolio Syndrome, Post-West Nile Virus

This condition may arise many decades after a polio infection. Long-term damage to motor neurons can result in eventual muscle weakness and atrophy, along with many other symptoms. Massage therapists are less likely to work with clients who have postpolio syndrome now than in previous decades, because new infections of the virus were essentially eradicated in the US by 1979. However, recent drop-offs in vaccinations have led to the identification of new polio cases in recent years. West Nile virus (WNV), a type of encephalitis that spreads from birds and horses to humans, caused a major outbreak in the US in 1999. It still causes new infections but on a smaller scale. Some survivors of WNV now show sequelae that look a lot like postpolio syndrome.

Irritable Bowel Syndrome

Some researchers now link a history of exposure to Giardia intestinalis, a water-borne parasite, to the eventual development of irritable bowel syndrome (IBS). This doesn’t mean all people with IBS had giardiasis, or that all people with a history of giardiasis will develop IBS, but it does open some new lines of inquiry and possibly treatment options for this common and painful condition. 

Many other infectious agents also have a documented history of causing long-term sequelae. The short list of pathogens associated with PAIS are listed below:

• Brucellosis 
• Chikungunya 
• Coxsackie B virus 
• Cytomegalovirus 
• Dengue fever 
• Ebola 
• Influenza 
• Human herpesvirus-6
• Lyme disease 
• Malaria 
• Q fever (Coxiella burnetii)
• Polio 
• SARS 
• Toxoplasmosis 
• Viruses that cause common cold 
• West Nile virus 

Theories About PAIS Mechanisms

In the work being done to unravel the mysteries of PAIS, there are four main theories about how this situation occurs. Those theories are:  

• Undetectable (by current methods) remnants of the initial pathogen may remain in the tissues and continue to elicit an immune system response, with subsequent inflammation and other consequences. Elements of both innate and adaptive immune responses have been seen in tissue studies, with T cells, B cells, and nonspecific white blood cell activity.
• The initial infection causes an autoimmune response. Autoantibodies are proteins manufactured by B cells that attack our tissues. These have been seen after COVID-19 infections, and this may be happening in other forms of PAIS as well. An argument could be made that many autoimmune diseases associated with a history of exposure to a specific pathogen (including multiple sclerosis, lupus, rheumatoid arthritis, and others) are examples of PAIS.
• The microbiome—specifically of the gut, but we can look in other areas too—is a carefully balanced environment of bacteria, viruses, and fungi that keep each other in check and keep unwelcome invaders out. Disruptions in the microbiome can, in theory, allow latent DNA viruses (like EBV, which is associated with ME/CFS) to reactivate. 
• Permanent tissue damage causes long-lasting symptoms. Especially in the case of COVID-19 or severe respiratory infections, lung and heart damage can impair blood and oxygen delivery to the tissues. Naturally, this can contribute to fatigue, poor exertion tolerance, and low stamina, and these symptoms may take months or longer to resolve—if they ever do. 

What Does This Mean for Massage Therapy?

It’s difficult to say how all this information about PAIS applies to judgments about massage therapy. Those judgments are typically derived from a combination of sources. First and foremost, clinical decisions must be driven by the client’s realistic hopes and goals for what they want to accomplish by receiving massage. Beyond that, we rely on what we know about safety issues, established conventional treatment options, medications and their predicted side effects, and the proposed effects of massage therapy. Sometimes, research on the topic helps guide some choices. But in the available material on PAIS, almost no information addresses variables that might inform massage therapy choices. Research is being done to elucidate the causes of PAIS, which researchers hope will lead to an eventual cure. But reports of successful treatment strategies for people experiencing these conditions today are remarkably lacking.

This leaves us to fall back on recommendations for massage therapy as currently practiced for the most common version of a PAIS, CFS—but this does not account for the countless other ways that postinfection syndromes may affect patients. 

As a starting place, here is a summary of possible risks, benefits, and appropriate accommodations in massage therapy for clients with CFS, as presented in A Massage Therapist’s Guide to Pathology, seventh edition:

Risks

Clients with CFS tend to have low stamina and poor resilience and may not welcome a rigorous, long, demanding massage. Such a session could leave them more fatigued after their treatment than before.

Benefits

Evidence suggests that massage therapy can help with pain, sleep, and anxiety—all issues for clients with CFS. Poor exercise tolerance may also respond well to gentle massage therapy. More rigorous bodywork can be helpful for clients who have more physical resilience.

Accommodations

With clients who have CFS, it’s critical that massage therapists be sensitive to their levels of energy and resilience, and not challenge them beyond their capacity. Many patients welcome focus on exercise recovery and sleep quality. 

The guidance about overtreatment is universally applicable for clients who have PAIS of any kind, and bodywork must always be gauged to stay within a client’s ability to adapt to changes in their external environment (e.g., with hot stones, ice massage, or other hydrotherapy applications), and in their internal environment (e.g., with maintaining blood pressure and equilibrium for people with dysautonomia). In addition, we must be aware that PAIS may involve a host of other troubling symptoms like digestive upset, headaches, shortness of breath, insomnia, vertigo, or others. These symptoms may demand a different kind of accommodation, and it may change from one day to the next. 

It’s safe to predict that as PAIS gets more attention, massage therapists may find that many clients identify as part of the PAIS community. And because our work often fills gaps where conventional medicine feels unsatisfactory, we may be able to offer relief and ease for people who feel they have run out of options. I hope to see our profession take up this challenge with compassion, curiosity, and a commitment to stay on top of developing information, so we can bring our best to the table.  

Resources

Backman, I. Yale School of Medicine. “The Long History of Long COVID and Other Chronic Illnesses.” October 31, 2023. https://medicine.yale.edu/news-article/the-long-history-of-long-covid-and-other-chronic-illnesses.

Bannister, B. A. “Post-Infectious Disease Syndrome.” Postgraduate Medical Journal 64, no. 753 (1988): 559–67. www.ncbi.nlm.nih.gov/pmc/articles/PMC2428896.

Choutka, J. et al. “Unexplained Post-Acute Infection Syndromes.” Nature Medicine 28, (May 2022): 911–23. https://doi.org/10.1038/s41591-022-01810-6.

Collingwood, J. “An Overview of Post-Viral Syndrome.” Southern Medical Association. August 16, 2021. https://sma.org/post-viral-syndrome.

Gandhi, M. “Post-Viral Sequelae of COVID-19 and Influenza.” The Lancet Infectious Diseases 24, no. 3 (December 2023): 218–9. https://doi.org/10.1016/S1473-3099(23)00762-4.

Guo, C. et al. “The Microbiome in Post-Acute Infection Syndrome (PAIS).” Computational and Structural Biotechnology Journal 21 (August 2023): 3904–11. https://doi.org/10.1016/j.csbj.2023.08.002.

Johnson, J. Medical News Today. “What to Know About Post-Viral Syndrome.” Last modified January 26, 2024. www.medicalnewstoday.com/articles/326619.

Kahn, K. MedPage Today. “ ‘Long Flu’ Is Real—But Long COVID Is Worse, Study Shows.” December 15, 2023. www.medpagetoday.com/infectiousdisease/uritheflu/107898.

MacMillan, C. Yale Medicine. “Long COVID, ‘Long Cold’: What to Know About Post-Acute Infection Syndromes.” October 17, 2023. www.yalemedicine.org/news/long-covid-long-cold-post-acute-infection-syndromes.

Pelc, C. Medical News Today. “Long COVID Fatigue Linked to Malfunctioning Mitochondria.” October 13, 2021. www.medicalnewstoday.com/articles/long-covid-fatigue-linked-to-malfunctioning-mitochondria.

Pugle, M. Verywell Health. “What Is Post-Viral Syndrome?” January 23, 2023. www.verywellhealth.com/post-viral-syndrome-6890118.

Shere-Wolfe, K. D. et al. “A Multimodal Ayurveda and Mind–Body Therapeutic Intervention for Chronic Symptoms Attributed to a Postinfectious Syndrome: A Pilot Study.” Journal of Integrative and Complementary Medicine (October 2023). https://doi.org/10.1089/jicm.2023.0234.

Spriano, P. Medscape. “What Are the Signs of Post-Acute Infection Syndromes?” June 17, 2022. www.medscape.com/viewarticle/975826.

Westermeier, F. et al. “Editorial: Current Insights Into Complex Post-Infection Fatigue Syndromes With Unknown Aetiology: The Case of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Beyond.” Frontiers in Medicine 9 (February 2022). www.frontiersin.org/articles/10.3389/fmed.2022.862953.