Researchers, clinicians, and advocates gathered for the inaugural conference of the International Society for Long COVID and Post-Acute Infection Syndromes in the Netherlands in late August. The four-day event featured hundreds of presentations and posters about trials and disease mechanisms.
Key points you should know:
- In late August, the International Society for Long COVID and Post-Acute Infection Syndromes hosted its inaugural gathering in Amsterdam. Hundreds hobnobbed in the H’ART Museum, a major cultural and conference facility in the heart of the city.
- Presenters acknowledged that a series of clinical trials had produced disappointing results. They focused on seeking lessons from the null findings and called for more smartly designed trials targeting the pathological mechanisms believed to be involved.
- Some presenters highlighted innovative use of electronic wearables and remote monitoring in an effort to improve research and accurately track biological events, such as the occurrence of post-exertional malaise.
- PROBE-PASC, a program centering mechanistic trials for Long COVID funded by the U.S. Department of Defense, was revealed during the conference.
In late August, hundreds of researchers, clinicians, advocates, and others gathered in Amsterdam for the inaugural conference organized by the recently created International Society for Long COVID and Post-Acute Infection Syndromes (ISLC-PAIS). Led by conference chair Rob Wust, a professor of muscle physiology at VU University Amsterdam, the event took place at the H’ART Museum, a major cultural and conference facility on the banks of the Amstel canal.
The four-day event marked the public debut of the ISLC-PAIS. The society’s core mission, according to its website, is “to integrate Long COVID and post-acute infection syndromes into mainstream medicine — bridging science, clinical care, and lived experience through rigorous, patient-partnered evidence.” Throughout the event, presenters highlighted the links among the diseases under discussion and argued that viewing them through a common lens made sense.
In his opening remarks, Ziyad Al-Aly, director of clinical epidemiology at the Veterans Affairs St. Louis Health Care System and a professor at the Washington University School of Medicine, explained that Long COVID is the latest example of a well-known historical phenomenon.
“The idea that infections or pandemics leave in their wake a wave of people, millions of people, with disability and disease is not really new,” Al-Aly said in a subsequent interview, citing reports of prolonged and disabling illness after worldwide flu epidemics in 1889–90 and 1918–20.
The conference covered the broad range of proposed biomedical mechanisms thought to be involved in the various presentations of Long COVID, including viral persistence, immunological dysregulation and autoimmunity, neurological disruptions, and vascular damage. Many panels highlighted research on myalgic encephalomyelitis (ME), either on its own or as a Long COVID phenotype.
Beyond the hard science, other sessions focused on clinical care, public health policy, and research funding challenges. In between the formal discussions, attendees schmoozed with colleagues over coffee and pastries, checked out the more than 100 poster presentations, or — weather permitting — strolled along the nearby canals. The organizers implemented some clean air precautions and made masks readily available, although they did not require participants to wear them.
David Putrino, a neuroscientist at Mount Sinai in New York, closed out the event on an optimistic note while acknowledging the challenges and the lack of simple answers. He described the clinical case definitions, proposed biological drivers, and the continuing efforts to find effective medications.
“We need to run toward complexity, not run away from it,” he concluded. “Anyone who is trying to look for the one magic bullet that will solve all of this is bound to be disappointed, because they’re trying to squeeze a square peg in a round hole.”
A “patient recap session” on the last day of the event will be available on the organization’s website. Long Covid The Answers also posted interviews with many of the conference speakers on its Facebook page.
Call for “mechanistic trials”
In a keynote talk called “Mechanisms First: How PAIS Trials Must Evolve,” Michael Peluso, an associate professor of medicine at the University of California, San Francisco, acknowledged that clinical trials to date have not led to improvements in symptoms.
These disappointing results, he said, indicated that trials needed to be more narrowly designed to target the specific pathological mechanisms believed to be driving the illness. “The best way to understand the biology of the disease is … to disrupt the pathways we think are at play to see what happens,” he said.
When such mechanistic trials yield null results, Peluso suggested, investigators should consider multiple circumstances that could possibly explain the findings. Perhaps the drug didn’t reach the target, or the dose was too low, or the intervention too late. After those and other factors are taken into account, said Peluso, should investigators entertain “the last option”— that the mechanism itself is wrong.
Peluso took the opportunity to make some news, announcing an $8 million grant from the U.S. Department of Defense for PROBE-PASC, a new Long COVID program focused on this type of mechanistic trial, as The Sick Times previously reported. The first trial will test the monoclonal antibody Pemgarda along with the immune-modulating drug hydroxychloroquine. The results from this and subsequent PROBE-PASC studies will inform larger treatment trials, said Peluso.
The best way to understand the biology of the disease is … to disrupt the pathways we think are at play to see what happens.
Michael Peluso, UCSF, investigator for PROBE-PASC
A number of investigators offered information about recent or ongoing clinical trials. Romina Foster-Bonds, the director of research and implementation at Scripps Research, presented an update on the Long COVID Treatment Trial-Tirzepatide (LoCITT-T). She and her colleagues described the trial in a preprint posted the week before the conference, although they have not yet published any results. (Julia Moore Vogel, one of the trial’s lead investigators, is on The Sick Times’ advisory board.)
Tirzepatide, a GLP-1 drug, is widely prescribed to treat diabetes and has been found to be helpful for other conditions. The double-blind, placebo-controlled trial is assessing whether the drug’s anti-inflammatory properties can impact Long COVID symptoms, particularly fatigue. Keeping the needs of homebound patients in mind, the trial is being conducted entirely remotely — the use of wearable electronic monitors, at-home blood collection trips, smart scales, and related adaptations have eliminated the need for on-site visits.
With this “direct-to-participant” model, the trial recruited more than 1000 participants in 73 days. Baseline data indicate that the trial population is more severely disabled than in many other studies. Although the results have not yet been released, adherence has been strong, with more than 95% of participants providing data at the six-month mark.
Chiara Amoroso, a researcher at Ospedale Policlinico di Milano, provided details on a small pilot trial of VSL#3, a high-dose probiotic. The team launched the trial based on evidence of changes in the gut microbiome associated with Long COVID, and they published their findings right before the conference in the British Journal of Biomedical Science.
Of the 48 participants, 23 received the probiotic for four weeks and 25 received the placebo, with change in fatigue scores as the primary endpoint. The treatment group reported a 24% reduction in fatigue compared to 6% in the control group, while 68% of those in the treatment group were counted as “responders” compared to 36% in the control arm.
The reported benefits continued for four weeks after the end of treatment. Associated changes in the composition of the microbiome were also identified, suggesting that targeting the bacterial population in the gut might be a useful therapeutic approach.
Discussion of PEM
In a session focused on “mechanism of PEM,” researcher and conference chair Rob Wust noted that post-exertional malaise (PEM) was heterogeneous and challenging to identify. “Patients tell us that PEM comes in many different flavors,” he said. “We don’t have really good diagnostics.”
Wust cited a 2024 study in Nature Communications in which he and colleagues reported damage in muscle tissue of people with Long COVID following an induced episode of PEM. Some critics had suggested the findings could be due to deconditioning from lack of activity rather than muscle injury. “We wanted to tackle that,” said Wust.
He presented data from a follow-up paper, published in July, that compared muscle changes found in people with Long COVID and ME and those induced by extended bed rest. Among other differences, patients experienced distinct changes in the type of fiber found in their muscles, while those in the bed rest group did not. The findings, said Wust, indicate that “the underlying mechanisms differ.”
At the same session, Mark Faghy, professor of clinical exercise physiology at Loughborough University in the U.K., noted that PEM can appear in multiple phenotypes, including “metabolic dominant,” characterized by physical fatigability and delayed recovery; “anatomic dominant,” by orthostatic intolerance, dizziness and cardiovascular issues; and “cognitive dominant,” by impaired memory, concentration, and executive function. Another variant, “multisystem” PEM, involves the “simultaneous exacerbation” of a broad spectrum of symptoms.
To address this heterogeneity, Faghy outlined a “systems-level framework” for understanding and studying PEM. He contrasted this with the standard research approach of focusing on a single pathophysiological pathway rather than on the complex relationships and feedback loops that result from interactions between malfunctioning systems.
In one slide, Faghy depicted the dense web of mutually reinforcing factors that lead to obesity, suggesting that a similar approach could prove fruitful in unraveling the causes of PEM. “Maybe we need to take a step back and view the bigger picture,” he concluded, framing his talk as a “call to action” to his colleagues.
“Maybe we need to take a step back and view the bigger picture,” he concluded, framing his talk as a “call to action” to his colleagues.
Mark Faghy, Loughborough University
Katherine Huang, a postdoctoral researcher at the University of Melbourne in Australia, described an ongoing study of “remote wearable monitoring of [PEM] in daily life.” For eight weeks, participants report their symptoms in a daily log, and wrist-worn devices measure heart rate, heart rate variability, sleep, respiratory rate, and step count.
By combining the data, the researchers can calculate more than 100 specific features that characterize PEM, such as how someone’s heart rate changes over steps taken, or how much time they spend in heart rate zones above their resting heart rate. The investigators have collected data from 56 participants and hope to answer questions like how often PEM occurs, whether it has an associated physiology, and whether it can be predicted with digital signals.
The PEM session included two other presentations. The first, by Ole Hensel, a neurologist at Martin Luther University Halle-Wittenberg, in Halle, Germany, examined “delayed muscle oxygenation and recovery” in people with Long COVID during handgrip exercise. The second, by Leonardo Tamariz, a physician and assistant professor at the University of Miami, highlighted similarities in altered energy metabolism in Long COVID, ME, and Gulf War illness, with increased use of carbohydrates relative to fat.
Patient-researcher surveys show a severe lack of care for ME
The Norwegian ME Association has around 6,500 members and a long history of advocacy. In seeking to impact public health policy, the organization releases surveys and other research into patients’ needs and attitudes, experiences of diagnosis and treatment, and access to services — or lack thereof. At the conference, the association, in collaboration with other Norwegian researchers, provided snapshots of the domestic situation in a few separate posters and an oral presentation.
Trude Schei, the association’s deputy chief executive director, gave the talk, which focused on “delayed recognition of pediatric ME/CFS and PEM.”According to a 2024 survey, only half of more than 600 people whose symptoms began before age 18 received a diagnosis within five years. The survey found that the time between symptom onset and diagnosis actually increased over the decade prior.
Some qualitative responses suggested hospitals were more reluctant than previously to render the diagnosis. Survey respondents said they experienced self-doubt and guilt and pushed themselves too hard in the period before they received a diagnosis. They reported that receiving a diagnosis was essential to obtaining school accommodations, such as home teaching, flexibility on in-person attendance, and transportation assistance.
“I think children’s lives are taken away from them by not giving them the right diagnosis quickly,” Schei wrote to The Sick Times. “It means they do not get understanding and support from family, friends and school, they do not get the right advice about energy management, and they deteriorate.”
Schei was also a coauthor of a few poster presentations. One of them — “Rising ME/CFS-related morbidity?” — found a peak in self-reported onset of symptoms in 2022 compared to earlier years, suggesting the impact of the Long COVID wave.
An examination of patient registries also found a large increase in the numbers seeking treatment for fatigue. This combined information from survey and registry data, the team concluded, “strengthens the inference that fatigue-related morbidity in Norway has increased substantially since the start of the COVID-19 pandemic.”
The Norwegian ME Association’s other poster presentations included one about PEM-related challenges, based on a survey of more than 1,000 respondents. Only 4% of people with severe ME in the survey reported they felt they had received “adequate” healthcare.
I think children’s lives are taken away from them by not giving them the right diagnosis quickly. It means they do not get understanding and support from family, friends and school, they do not get the right advice about energy management, and they deteriorate.
Trude Schei, Norwegian ME ASsociation
Online protests greeted the conference
Before and during the gathering, organizers and speakers faced fierce criticism on social media regarding a number of controversial issues.
In the days leading up to the conference, some Long COVID activists complained about the decision to include their illness under the PAIS umbrella, arguing that it is unique and should not be lumped into the larger category.
Once the meeting began, the online focus shifted to masking practices. The venue featured air filtration and disinfection systems, ventilation was monitored continuously, and most participants did not mask. When photos of unmasked attendees appeared on social media, some people expressed serious disappointment and dismay at that decision.
The public exchanges included some crude and offensive comments from both sides that exacerbated the situation. In a thread posted on X afterward, Mount Sinai neuroscientist David Putrino addressed the tense atmosphere, acknowledged the importance of the concerns being raised, and appealed to everyone to express themselves as respectfully as possible.
“We have an opportunity, collectively, to be part of a solution to problems that have caused untold and horrific suffering for millions of people for decades,” he wrote. “Let’s meet this moment and change the face of medicine. Together.”
David Tuller is a senior fellow in public health and journalism at the Center for Global Public Health at the University of California, Berkeley. His academic position is supported by crowdfunded donations to UC Berkeley, largely from people with ME/CFS and, more recently, Long COVID.
Editor’s notes: Tuller presented a poster on methodological flaws in biopsychosocial research into ME/CFS and Long COVID at the ISLC-PAIS conference, but covered his own registration fee, travel, and lodging expenses. In 2018, the Norwegian ME Association hosted him for several days of talks in Oslo, and paid for his airfare and expenses.
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