Live blog: Following the Spring 2025 PolyBio Symposium on Long COVID and related diseases

Leading scientists studying Long COVID and related chronic diseases are set to present updates to their work on Friday at the PolyBio Research Foundation’s Spring Symposium. The Symposium is a packed day of virtual presentations discussing studies into Long COVID’s underlying biology, updates to clinical trials, and research on other complex chronic diseases.

The PolyBio Research Foundation is a leading funder of innovative Long COVID research, and its projects are closely watched by many in the Long COVID community. Through its Long COVID Research Consortium, PolyBio supports projects at institutions across the U.S. and internationally, and fosters collaboration between scientists working on related topics. Some projects also support developments in clinical care.

Many PolyBio-funded projects focus on the underlying causes of Long COVID and related diseases, such as myalgic encephalomyelitis (ME) and chronic Lyme disease. These include research spanning many organ systems, and projects studying potential biomarkers, animal models, and treatment options, according to the organization’s interactive Consortium Project Explorer page. A core goal for many projects is understanding how reservoirs of SARS-CoV-2 remain active in the body and contribute to symptoms long after infection — a theory known as viral persistence.

As we did for the foundation’s previous Symposium last fall, The Sick Times’ team will be following the presentations throughout the day. Check this article and our social media pages to find our takeaways from the presentations.

— Betsy Ladyzhets

Table of contents (click to jump to each section):

• 11 a.m. to 12 p.m. ET: Amy Proal (intro), Resia Pretorius, John Wherry, David Price, Johan Van Weyenbergh
• 12 p.m. to 1 p.m. ET: Michael Peluso, Nadia Roan, Lael Yonker, Christopher Dupont, Gene Tan
• 1 p.m. to 2 p.m. ET: Marcelo Freire, Michael VanElzakker, Francis Eun Lee, Timothy Henrich, Huaitao Cheng
• 2 p.m. to 3 p.m. ET: Akiko Iwasaki, Victoria Cortes Bastos, Mario Murakami, Sara Cherry, Saurabh Mehandru
• 3 p.m. to 4 p.m. ET: Esen Sefik, Melanie Walker, Steven Deeks, Shannon Delaney, Shannon Stott
• 4 p.m. to 5 p.m. ET: David Izquierdo Garcia, David Putrino, Silvia Lucena Lage, Zian Tseng, Benjamin Readhead
• 5 p.m. to 5:30 p.m. ET: Max Qian, Daniel Chertow, Amy Proal (conclusion)

Editor’s note: The PolyBio Research Foundation, like The Sick Times, has received support from the Balvi and Kanro funds. Our newsroom operates independently of financial supporters.

5 p.m. to 5:30 p.m. ET

Max Qian with University of California, San Diego’s J. Craig Venter Institute (JCVI) presented further results of his team’s work using machine learning to identify different Long COVID symptom clusters, endotypes, and severity groups. To do that, they’ve been using data from four surveys, and have so far come up with 16 symptom clusters, eight endotypes, and three severity groups (mild, moderate, severe). In his presentation, Qian shared an analysis of combined survey data compared to an analysis of Cardiff clinic survey results. He also showed his team’s analysis of data from the Cardiff survey, which showed that most patients fall into the moderate category. His team’s next steps are mapping results across the last site (UCSF) to analyze them across all four survey sites and develop a longitudinal analysis before finishing the research manuscript. 

The last presenter, Daniel Chertow, presented on behalf of the National Institutes of Health Clinical Care Center. He shared details about an upcoming clinical trial they’re hoping to recruit for, emphasizing that controls — adult participants previously infected with COVID but who didn’t sustain prolonged symptoms — are most needed. 

The pilot trial will include six people with Long COVID and six controls, and is focused on collecting tissue for biopsy from varying sites in the body to evaluate the relationship between SARS-CoV-2 protein persistence and Long COVID. Proal emphasized the importance of spreading the word to recruit controls, calling it “the most impactful thing for the space” and mentioning travel and additional compensation. Angelique Gavin is the contact point for interest: angelique.gavin@nih.gov or 301-402-0880.

Proal concluded the symposium by thanking researchers, patients, control participants, and donors, saying that she looks forward to the next symposium in six months. “In my opinion, there continues to be great energy not just in the Long COVID space, but in the entire IACC [research] community,” she said.

— James Salanga

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4 p.m. to 5 p.m. ET

The Symposium’s last full hour started with Harvard’s David Izquierdo Garcia sharing early updates from a study using positron emission tomography (PET) to better understand microclots. PET, also discussed earlier in the day by Timothy Henrich, is an imaging technique that measures metabolic systems. Garcia and his colleagues hypothesize that PET could be used to detect microclots in vivo, meaning in living tissue. They have just started collecting samples, but early imaging results are promising so far, he said.

Next, David Putrino from Mount Sinai’s CoRE shared brief updates on nine clinical trials currently in different stages of recruiting and analysis at the center. (Putrino was on the schedule for later in the day, but took the place of Chiara Giannarelli from New York University, who couldn’t make it to the event.)

The trials include three devices and six drugs or supplements:

• A novel device by Humanity Neurotech that aims to disrupt cognitive symptoms, for people with Long COVID;
• Varus nerve stimulation, for people with Long COVID and dysautonomia;
• A pain reliever device by Sana Health, for people with chronic Lyme;
• HIV drugs Maraviroc and Truvada, for people with Long COVID;
• Lumbrokinase, an enzyme that may help break down blood clots, for people with Long COVID, ME, and chronic Lyme;
• Low-dose rapamycin, for people with Long COVID;
• Supplemental oxygen, in an open-label case series (meaning anyone who might benefit from the treatment can try it, and researchers will share data if it appears to be helpful);
• V-nella, a probiotic supplement, also in an open label case series.

Most of the trials require participants to live in the New York area, except for the Sana Health trial, which is entirely remote. The vagus nerve stimulation trial is already complete, and researchers are now analyzing the data. Overall, the trial did not find that the stimulation device was more helpful than a placebo in reducing symptoms across all participants, but the CoRE team are analyzing data in subgroups to identify which participants had better success with it, Putrino said. He added that the team is planning more trials.

Then, Silvia Lucena Lage from the National Institute of Allergy and Infectious Diseases (NIAID) shared results from a recent study of how SARS-CoV-2 impacts the immune and metabolic systems. The study included participants with Long COVID and those who had recovered from acute infections, as well as healthy controls. Lage and her colleagues found both similarities and differences between the Long COVID and recovered groups; while those with Long COVID had more clear dysfunction in their immune and metabolic systems, the virus had a significant, lasting impact even on those who did not report long-term symptoms, she said.

Zian Tseng from University of California, San Francisco (UCSF) next discussed a unique, in-progress study examining the potential relationship between COVID-19 and sudden cardiac deaths. Since 2011, UCSF has worked with the San Francisco medical examiner’s office to study sudden cardiac deaths with in-depth autopsies. As the project has continued following the start of the pandemic, it now includes many people who had SARS-CoV-2 infections at some point before their death. To date, Tseng and colleagues have processed 45 post-2020 sudden death cases and matched them to 42 pre-2020 cases, conducting detailed analysis of each one. Results so far have shown some evidence of SARS-CoV-2 viral reservoirs, but the study is still in early stages, Tseng said.

Finally, Benjamin Readhead from Arizona State University discussed a potential connection between viral infections and Alzheimer’s disease. Upon investigating why a specific group of Alzheimer’s patients had increased amounts of an antibody, called IgG4, in their guts, Readhead and his colleagues found that these patients had a virus called cytomegalovirus, or CMV, in their brains. CMV is a common virus that typically does not cause issues, but can be dangerous for people with weakened immune systems. Benjamin said these findings suggest there may be a role for antivirals in treating some people with Alzheimer’s, though he stressed that scientists must first develop biomarkers to identify who may be a good fit for such treatment.

— Betsy Ladyzhets

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3 p.m. to 4 p.m. ET

Esen Sefik of Yale University gave updates on her work studying a humanized mouse model of SARS-COV-2 RNA persistence. She explained that these humanized mice “harbor [a] human immune system” from transplants of human metabolic and stem cells. “These mice are really useful as platforms for therapeutics,” she said. By using these animal models, her team is attempting to determine if the blood of people with Long COVID harbors persistent SARS-CoV-2 virus. 

The vagus nerve is a “huge cesspool,” said Melanie Walker of the University of Washington. Walker has been collecting samples from the vagus nerve and ganglia — during the organ transplant process — to analyze for proteins from pathogens that may be associated with the nerve. This might provide more insight into neurodegenerative diseases  like Alzheimer’s and Parkinson’s: “We might be able to really narrow down our search for the origins and the progression of many of these diseases if we understood the vagus nerve a little better,” she said. Amy Proal expressed excitement about the study, calling the vagus nerve a “superhighway” for organisms between the body and the brain.

Next, Steven Deeks of UCSF spoke about a new program called VIPER that will enroll 150 people to try and find biomarkers for Long COVID. They’re collaborating with a similar program that helped find and validate biomarkers for HIV. Twice weekly for four weeks, their team will conduct gut biopsies and collect accessible fluids like blood, saliva, and stool from people with Long COVID and controls to examine potential SARS-CoV-2 reservoirs. The program’s goal is to find an accessible, validated biomarker, like a blood or saliva test. “We intend to disrupt the current way that we go about developing assays for Long COVID,” he said.

Researcher Shannon Delaney of Lange Neurology talked about a study she and her team conducted that found people with psychosis were three times as likely to have Bartonella DNA in their blood compared to healthy controls. She’s been working with Mount Sinai’s CoRE to also look for Bartonella in people with Long COVID and ME, which Proal hopes they will be able to present at the next PolyBio Symposium.

Finally, Shannon Stott of Harvard Medical School gave a presentation on a high-tech device in “microfluidics” work that she and her team created that can capture intact SARS-CoV-2 particles. “We’re cancer biologists,” she said, “We were so excited to think of using this [technique] because we think it’s a terrific fit to look at monitoring viral loads and Long COVID samples. She described her session as a “trailer” and aims to plan for updates at the next symposium.

— Miles Griffis

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2 p.m. to 3 p.m. ET

Yale University’s Akiko Iwasaki kicked off the 2 p.m. timeslot by discussing her research transferring antibodies (or IgG) from Long COVID patients to mice to try to replicate disease symptoms. Some of her team’s more interesting findings came from administering the “hot plate test” to mice who’d been injected with IgG from Long COVID patients with chronic pain. The mice in the control group took around ten seconds to respond to the hot plate; the mice with the Long COVID IgG showed persistent sensory hypersensitivity and reduced locomotor activity. Those mice responded in as few as five seconds to the hot plate. She said one of the next steps of this research will be trying targeted therapeutic interventions to control IgG activity.

Victoria Cortes Bastos, also from Yale, summarized the findings of her paper published today in The Journal of Immunology. Bastos’ team enrolled 40 participants with ME and 41 matched healthy control subjects at the Bragée Clinic in Sweden. They assessed plasma samples and cerebrospinal fluid and were able to distinguish different immunotypes of ME, along with 2 separate patient clusters. She hopes to continue this research to build a group of evidence about distinct underlying mechanisms for similar disease symptoms. 

Much like Bastos, Mario Murakami of Harvard Medical School is investigating how different drivers can produce similar symptoms in patients with IACCs. He said that while we’re beginning to understand the beginning of the story (viral persistence, autoimmunity, etc.) and the end of the story (IACC symptoms like pain, brain fog, and fatigue), we’re missing the middle of the story. His hypothesis is that vagus nerve dysregulation is what’s happening in the middle. Murakami’s team was able to see that persistent vagus nerve activation can cause a sensitization that could drive neuroinflammation. His next steps are to add datasets, include individuals with Lyme in his research, and to perform an analysis comparing cases against each other.

Sara Cherry from the University of Pennsylvania shared her research on viral RNA reservoirs in the gastrointestinal tract. In trying to understand how SARS-CoV-2 infects the gut, Cherry hopes to find a way to use antivirals to stop the virus from continuing to shed in the gut and to drop the viral load. Her team found that commonly used antivirals, such as Paxlovid, are very active in the lung cells, but not in the cells in the intestinal tract. They will continue their research with human patients and with the longitudinal cohort of non-human primates and mouse model studies already underway.

Saurabh Mehandru‘s research at Mount Sinai also focuses on the gastrointestinal tract. His team conducted the first placebo-controlled, randomized trial of a SARS-CoV-2-specific monoclonal antibody in people with Long COVID. Their team found the intestines lack a potent immune response to SARS-CoV-2. He said abnormalities seen in people with Long COVID could reflect viral persistence or prolonged immune dysregulation in the intestines, due to the way the gut “seems to be tolerant of the virus.” His team plans to continue their tissue-based analysis, including a type of advanced sequencing using single-cell RNA. 

— Heather Hogan

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1 p.m. to 2 p.m. ET

In the third hour of talks, Marcelo Freire of JCVI first spoke about skin punch biopsy samples — samples of the skin, a technique often used to test moles or similar small areas — his team have taken from people with Long COVID and related diseases like ME, post-treatment Lyme disease, and Ehlers-Danlos Syndrome. His team analyzed samples for small fiber neuropathy, a condition frequently seen in Long COVID in which damage to small nerve fibers in the skin can lead to an inability to feel pain or temperature, as well as disrupt common autonomic functions. His lab uses a technique called spatial transcriptomics to identify pathogens like SARS-CoV-2.

“Brain fog” is a common “nonspecific” symptom of many chronic diseases, including Long COVID, said Michael VanElzakker of Harvard Medical School. Through a series of high-tech neuroimaging techniques including those using magnetic resonance imaging (MRIs), his team found, in preliminary results,that both Long COVID and pre-COVID ME show changes to the brainstem. They specifically measured NAA, or N-Acetylaspartic acid, an amino acid derivative that plays an important role in neuronal health, where the vagus nerve connects to the central nervous system, he said.

Then, Francis Eun Lee of Emory University spoke about the use of a technology called MENSA, or Media Enriched with Newly Synthesized Antibodies, which her team uses to take an immune snapshot of the blood of people with Long COVID to help identify any pathogens that might be present. “We think this could potentially be an aid to diagnosis for Long COVID,” she said, explaining that it may also help in our understanding of other related diseases like ME. The testing is being used in Mount Sinai CoRE’s clinical trial of the HIV antiviral Maraviroc, for Long COVID.

Timothy Henrich of UCSF shared an update from projects using positron emission tomography (PET) imaging, a test that visualizes and measures metabolic function, as well as UCSF’s analysis of different tissue samples from people with Long COVID. These methods are making progress toward identifying different sub-groups within Long COVID. UCSF is also setting up a clinical trial, called INTERRUPT-LC, that will test the immunotherapy drug Anktiva.

Hauitao Cheng of the Karolinska Institute then presented preliminary results from a detailed analysis of immune system markers in the gut. The study focused on people with Long COVID who have gastrointestinal symptoms, in comparison to people who were receiving colonoscopies for other reasons. Cheng and his colleagues identified a few differences between the Long COVID and control groups, including changes in T-cell and B-cell composition and chronic inflammation in the gut. Further analysis is underway.

— Miles Griffis & Betsy Ladyzhets

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12 p.m. to 1 p.m. ET

Michael Peluso from the University of California, San Francisco (UCSF) started this hour with a highly anticipated presentation, sharing results of his team’s monoclonal antibody (mAb) clinical trial. Unfortunately, the trial was unsuccessful: there was no difference in primary or secondary outcomes between people who received the mABs and those who received placebos.

Discussing this disappointing result, Peluso noted that the mAb his team tested — called AER002 — was out of date by the time they studied it, as it was developed for early pandemic-era variants. This was also a different drug from those used in prior case reports showing success with mAbs for treating Long COVID, he said. Peluso additionally noted that participants in this trial were not specifically screened for viral persistence, and may not have been the best people to test this type of drug.

Peluso speculated that viral persistence may be a less promising avenue for Long COVID treatment than many researchers and advocates have long hypothesized, but emphasized that he is “not discouraged.” He shared recommendations for further trials (see the image above), adding, “I am confident that we are going to figure this out.”

Next, Nadia Roan, also from UCSF, discussed other findings from the university’s LIINC cohort. Similar to John Wherry’s lab, this group analyzed specific T-cells that respond to SARS-CoV-2 and other viruses. They found that SARS-CoV-2-specific T-cells from Long COVID participants appear to be more exhausted and have other notable differences from similar T-cells in other people. Their results support both SARS-CoV-2 persisting and reactivating other viruses after acute infection. Up next, they’ll be collecting reproductive tissue samples from women with Long COVID.

Then, Lael Yonker from Harvard Medical School shared results from her research into how Long COVID impacts the gut. While she focuses on children with Long COVID, her results also apply to adults. Her research has led her to look for a connection between neutrophils, a type of white blood cells, and microclots. Yonker is also leading a currently-in-progress pediatric clinical trial of Larazotide, which has been used as a successful treatment for multisystem inflammatory syndrome in children (MIS-C).

Yonker concluded with a reminder that clinical trials — moving slowly for adults — are going “even slower” for the millions of children with Long COVID.

Two researchers from the J. Craig Venter Institute (JCVI) discussed their work on new methods for analyzing complex chronic diseases. Opening his presentation, Chris Dupont said that “the way we think about infection may be inherently flawed,” in that infections are generally diagnosed with blood or saliva tests rather than tests that capture how pathogens may impact all parts of the body. Dupont and colleagues focus on analyzing microbiomes, the communities of microbes that live in people’s bodies; he described early results from a study looking at the microbiomes of people who received surgery for cranio-cervical instability.

Dupont’s colleague, Gene Tan, then discussed analyzing immune responses in people with Long COVID. He uses machine learning to identify different phenotypes, or potential sub-groups within people with Long COVID. His research has suggested that people with Long COVID have chronically high estrogen levels, a connection that he’ll investigate further.

— Heather Hogan & Betsy Ladyzhets

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11 a.m. to 12 p.m. ET

Amy Proal, president of PolyBio Research Foundation, kicked off the day with an overview of the presentations to come. Complex chronic disease research is “underfunded and understudied compared to the importance of the work,” she said, and PolyBio aims to counter that challenge with funding and collaboration.

Some of the presentations today will include “clear leads” into potential treatments, she said, along with research into diagnostic tests. Proal considers it unlikely that there will be a singular Long COVID biomarker, but there are “tests that can capture different drivers of disease in different patients,” she said. Some PolyBio-funded scientists are now comparing potential tests head-to-head. Another major focus for PolyBio at the moment is to understand the intersections of infections and neurodegenerative disease, like Alzheimer’s, she said.

Next, Resia Pretorius from South Africa’s Stellenbosch University offered updates on her group’s influential work studying microclots. Microclots, or tiny blood clots, can cause issues with oxygen circulation and potentially contribute to Long COVID symptoms. Pretorius and her colleagues are now focused on better classifying different types of microclots and understanding exactly how they may cause issues to different organ systems. Citing data from one recent study, she noted that microclots in people with Long COVID can potentially form macroclots, leading to strokes and other major cardiac issues.

Mark Painter, on behalf of the John Wherry lab at the University of Pennsylvania, then shared results from the group’s detailed analysis of T-cells, an important component of the immune system. Their work focuses on a very specific group of T-cells that respond to SARS-CoV-2 and other viruses like Epstein-Barr, which may be reactivated by SARS-CoV-2. The group has found that, in many people with Long COVID, these specific T-cells are activated for at least a year following infection — a response that’s distinct from those who recovered from infection. Notably, overall T-cell counts are not impacted by SARS-CoV-2; “generally, most of the T-cells look fine,” Painter said during the Q&A, noting that targeted analysis is needed to find the COVID-related changes.

David Price from Cardiff University in the United Kingdom presented next, discussing detailed analysis of the lungs of people with Long COVID. This group has analyzed patients’ lungs through different mechanisms, including proteomics (or studying which proteins are active). Proteomics analysis led the group to find a potential biomarker of breathlessness in Long COVID, which they validated in a second cohort of patients from the Karolinska Institute.

Finally, Johan Van Weyenbergh from the Rega Institute in Belgium presented findings from small, patient-led clinical trials of antivirals and anticoagulant therapies. Van Weyenbergh’s group tested Paxlovid, and found that it did lead to reduced symptoms for people with Long COVID over the 15 days of treatment; however, this improvement wasn’t maintained in months of follow-up. Still, the small trials offer lessons in co-designing trials with patients and identifying which people might benefit from which treatment, he said.

— Betsy Ladyzhets