Post-Acute Infection Syndromes


Post-acute infection syndromes (PAIS), also known as Infection-associated chronic illnesses (IACI) or conditions (IACC), encompass a group of diseases with overlapping symptoms. This term reflects the growing recognition that various infections can leave lasting and often debilitating effects, even after the initial illness has subsided.

Infections can leave lasting and often debilitating effects, even after the initial illness has subsided

Examples of PAIS include Long Covid (post acute sequelae of COVID-19 or PASC), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), persistent or posttreatment Lyme disease syndrome (PTLDS), and post sepsis syndrome (PSS). These diverse conditions share a common thread: they often emerge following an acute infection and present with long-lasting symptoms like severe fatigue, cognitive impairment, and dysfunction in multiple organ systems.

Beyond the shared experience of these debilitating symptoms, intriguing similarities exist in the proposed mechanisms of these diseases. Potential explanations include the persistence of pathogens or lingering invaders, dysfunctional immune responses, altered metabolic pathways, neurological inflammation, and disrupted microbiomes.

Given the remarkable parallels in symptom presentation and potential underlying mechanisms, a critical need exists to identify unique markers of these conditions and develop effective diagnostic tools and treatments. While significant challenges remain, a collaborative approach that transcends individual conditions and embraces the commonalities of PAIS holds immense promise. This unified effort can pave the way for a deeper understanding of these complex syndromes, ultimately leading to improved patient care and faster breakthroughs across the entire spectrum of PAIS.

Long Covid

Although most people infected with COVID-19 will recover completely and return to normal health, some people will develop Long Covid, a term used to describe the constellation of symptoms that persist or develop following infection with SARS-CoV-2. Long Covid can occur following severe, mild, or even asymptomatic infection and we also know that vaccinations only provide limited protection against developing this illness.

Taking into account some immune protection from vaccinations, in the face of the continual evolution of variants, we expected at least 1 in 10 people will experience Long Covid following COVID-19

Long Covid is a condition, which can involve a range of debilitating symptoms that can have adverse impacts on people’s lives. Symptoms vary widely, but the most common debilitating symptoms include fatigue, cognitive impairment, and exertion intolerance. That exact cause of disruption to the immune, nervous and vascular systems, virus that remains uncleared from the body, and the individual’s underlying health condition.

Estimating the global prevalence of Long Covid is a challenging task due to the complex nature of the condition and the difficulties in diagnosis and tracking. The lack of a universally agreed-upon definition for Long Covid, differences in research methodologies employed across studies, and the evolving picture of global data availability all contribute to a range of reported prevalence estimates. Current research suggests a range of 6% to 20%, with a central estimate hovering around 10%. It is crucial to remember that further research is necessary to refine our understanding of the true global prevalence of Long Covid and assess potential variations across different countries. Additionally, prevalence estimates can differ by country due to diverse populations and healthcare systems.

There is an urgent need to identify biomarkers of these syndromes so that diagnostic tools and treatment options can be developed 

In a subgroup under the Long Covid ‘umbrella term’, the condition is reminiscent of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS), given there is significant overlap between symptoms experienced by Long Covid and ME/CFS patients. One potential common mechanism behind these symptoms may be viral persistence or reactivation of latent viruses from an earlier infection (e.g. Epstein Barr Virus (EBV)).

Currently, there is no cure for these devastating conditions, and they have historically been medically neglected and underserved in research. Therefore there is an urgent need to identify biomarkers of these syndromes so that diagnostic tools and treatment options can be developed.


Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is a long-term, fluctuating neuroimmune disease that causes symptoms affecting many body systems, more commonly the nervous and immune systems. ME/CFS was formally recognised by the WHO in 1989, yet there are no universally effective treatments, only 6% of people fully recover and is more underfunded with respect to burden than any disease.

Only 6% of people fully recover and is more underfunded with respect to burden than any disease

People with ME/CFS experience debilitating pain, fatigue and a range of other symptoms associated with post-exertional malaise, the body and brain’s inability to recover after expending even small amounts of energy – and the hallmark symptom of this illness.

Typically, though not always, the illness will follow a viral or bacterial infection. The acute symptoms die down, but the exhaustion persists. There is a tendency for the severity of the illness to be “up and down”. At the severe end of the scale, patients are completely bed-bound and need to lie in quiet, darkened rooms, unable to perform self-care.


Before the pandemic there were between 17-30 million people living with ME/CFS around the world, including an estimated 25,000 people in New Zealand. However, COVID-19 has triggered a surge in the number of people affected by ME/CFS, and current estimates now suggest that over 55 million individuals are living with this debilitating condition.

The economic cost of ME/CFS is enormous – in the United States alone it is projected to cost the economy USD$36-51 billion per year.


The body’s fight against infection can be a double-edged sword. Sometimes, the response becomes overly agressive, leading to a life-threatening condition called sepsis. This can happen with severe COVID-19, which, like some other infections, triggers a similar reaction within the body.

Studying overlapping conditions offers valuable insights that can inform the research and treatment of each

While the initial symptoms of COVID-19, like fever, chills, and difficulty breathing, are well-known, the battle doesn’t always conclude with the virus being cleared. Many individuals recovering from COVID-19, especially those who experienced severe cases requiring hospitalization, can experience long-term effects.

Here’s where things get more complex. These long-term effects can manifest in several ways, depending on the severity of the initial illness. For those who required intensive care unit (ICU) support, a condition called Post-ICU Syndrome (PICS) can develop. PICS involves a range of physical, cognitive, and mental health challenges following critical illness.

However, another distinct condition, Long Covid, is increasingly recognized. Unlike PICS, which typically follows severe cases requiring ICU admission, Long Covid can affect individuals who had even mild COVID-19 cases.

Despite these distinctions, there are intriguing parallels between Long Covid, PICS, and post-sepsis syndrome. All three conditions represent the body’s struggle to fully recover after a significant infection. Studying these overlapping conditions offers valuable insights that can inform the research and treatment of each.