Years into the Long COVID crisis, millions remain disabled by an illness that medicine has struggled to name, let alone cure. Now, a coalition of researchers called the SPEAR Study Group has proposed a clinical trial using a monoclonal antibody, VYD2311, to pursue what they believe may be the disease's hidden engine: viral fragments persisting silently in the body long after infection has passed. The proposal, to be presented to the NIH's RECOVER-TLC initiative in September 2025, represents a philosophical turn in medicine — from managing suffering to confronting its source.
SPEAR Study Group Proposes Monoclonal Antibody Trial for Long COVID Using Invivyd's VYD2311
Long COVID patients remain disabled and unable to function in ordinary life, as described by patient advocate Melissa Walker.
Persistent viral fragments may be driving Long COVID—and antibodies might clear them.
Mark
So the SPEAR group is saying Long COVID is actually a chronic viral infection that never fully clears. Is that proven?
Mimi
Not yet—that's what they want to test. The hypothesis is that spike protein or viral RNA persists in some patients' bodies, and that persistence drives the symptoms. This trial would be the first large-scale test of whether monoclonal antibodies can clear that and improve outcomes.
Luke
Right, and that's important to flag. The persistent viral hypothesis is one theory among several. Some researchers point to immune dysregulation, others to microclots or organ damage. This trial is betting on one mechanism.
Mark
Why VYD2311 specifically? What makes it different from other antibodies?
Mimi
It's engineered to neutralize contemporary virus variants and has a pharmacokinetic profile that allows for intramuscular dosing over months, not just one-time infusions. That matters if you're trying to maintain high antibody levels long-term.
Luke
The company says that. We don't have clinical data yet showing it works better than alternatives for this specific use case. It's a candidate worth testing, but "best-in-class" is marketing language until the trial runs.
Mark
How many patients would be in this trial?
Mimi
More than 100 per arm—so at least 200 total, probably more. It's designed to generate definitive evidence, not preliminary signals.
Luke
And they'd only enroll patients with biomarkers of persistent spike or viral RNA. That's smart design—it focuses on the population most likely to benefit if the hypothesis is right. But it also means the results won't tell us whether monoclonal antibodies help Long COVID patients without those biomarkers.
Mark
When would we know if this works?
Mimi
The trial hasn't been approved yet. RECOVER-TLC has to fund it first. If approved, enrollment and follow-up could take a year or more. We're probably looking at 2026 or 2027 for results.
Luke
And that's assuming RECOVER-TLC agrees this is the right approach. They might want different endpoints, different patient populations, or different drugs. This is a proposal, not a done deal.
Der Puls
- Millions of Long COVID patients remain unable to work, exercise, or carry out basic daily life, with no proven treatment in sight — a quiet crisis that has lasted years without resolution.
- The SPEAR Study Group is challenging the prevailing symptom-management approach by arguing that lingering viral particles, not downstream dysfunction, are actively driving the disease.
- Their proposed trial would enroll only patients with measurable biomarkers of persistent spike protein or viral RNA, sharpening the hypothesis and raising the scientific stakes considerably.
- VYD2311, the antibody at the center of the proposal, is engineered to neutralize current variants and may be administered by injection rather than infusion, making long-term treatment more feasible.
- Drs. Amy Proal and David Putrino will bring this design before the NIH's RECOVER-TLC workshop in Bethesda on September 9–10, 2025, where funding approval could determine whether the trial moves forward.
- If the results support the viral persistence hypothesis, Long COVID treatment could shift from palliative care to targeted antiviral intervention — a potential turning point for an illness that has resisted understanding.
Years into the Long COVID crisis, millions remain disabled by an illness that medicine has struggled to name, let alone cure. Now, a coalition of researchers called the SPEAR Study Group has proposed a clinical trial using a monoclonal antibody, VYD2311, to pursue what they believe may be the disease's hidden engine: viral fragments persisting silently in the body long after infection has passed. The proposal, to be presented to the NIH's RECOVER-TLC initiative in September 2025, represents a philosophical turn in medicine — from managing suffering to confronting its source.
A coalition of researchers known as the SPEAR Study Group has put forward a formal proposal to test a monoclonal antibody treatment for Long COVID, arguing that the disease's persistent symptoms may be driven not by lasting damage alone, but by viral fragments still active in the body. Their candidate, VYD2311 — developed by Invivyd — is designed to neutralize circulating spike protein, and the group believes that maintaining high antibody levels in patients' blood over months could suppress what may be a chronic, low-grade viral infection.
The proposed trial is designed to be definitive rather than exploratory. The SPEAR group recommends enrolling more than 100 patients per arm in a randomized, placebo-controlled study, limited to those who show measurable biomarkers of persistent spike antigen or viral RNA. Success would be measured first by whether VYD2311 reduces detectable viral presence, and second by whether patients feel better as a result — linking biological mechanism directly to human outcome.
VYD2311 shares its structural backbone with other Invivyd antibodies that have already demonstrated clinical benefit, and its pharmacokinetic profile may allow for intramuscular injection rather than intravenous infusion, an important practical advantage for long-term use. Dr. Michael Peluso of the SPEAR group noted that no large-scale study has yet examined whether persistent viral material truly drives Long COVID, calling this a moment when the science and the tools are finally aligned.
Drs. Amy Proal and David Putrino will present the trial design to the NIH's RECOVER-TLC initiative at its Second Annual Workshop in Bethesda, Maryland on September 9–10, 2025. For patients like Melissa Walker, who described Long COVID as having stolen her ability to function in even the most ordinary parts of life, the proposal carries profound personal weight. If RECOVER-TLC approves funding and the trial succeeds, it could mark a fundamental shift — from treating Long COVID's symptoms to confronting what researchers believe may be its root cause.
A group of leading researchers has put forward a detailed proposal for testing a new monoclonal antibody treatment for Long COVID, betting that the disease's stubborn symptoms may stem from viral particles that linger in the body long after initial infection. The SPEAR Study Group, formed by investigators focused on persistent viral reservoirs, has recommended a clinical trial centered on VYD2311, an antibody candidate developed by Invivyd, designed to neutralize and clear circulating spike protein from the bloodstream of Long COVID patients.
The proposal reflects a shift in how researchers are thinking about Long COVID. Rather than treating it as a collection of symptoms to manage, the SPEAR group is proposing to target what they believe may be the underlying driver: fragments of the virus or viral RNA that remain active in the body months or years after the initial COVID-19 infection. The study design calls for maintaining high levels of neutralizing antibodies in patients' blood over an extended period—months, not weeks—to suppress what researchers suspect is a chronic, low-level viral infection fueling the disease.
The trial would be rigorous and large-scale. The SPEAR group recommends enrolling more than 100 patients per arm in a randomized, placebo-controlled study, powered to generate definitive evidence rather than preliminary hints. Enrollment would be restricted to patients who show biomarkers of persistent spike antigen in their blood or viral RNA in tissue samples, ensuring the trial focuses on people whose biology aligns with the hypothesis being tested. The primary measure of success would be whether VYD2311 can reduce detectable spike antigen or viral RNA, with secondary measures tracking whether patients experience symptom improvement as that underlying infection is suppressed.
VYD2311 itself is a next-generation antibody engineered using Invivyd's proprietary platform to neutralize contemporary virus variants. The drug's pharmacokinetic profile—the way it moves through and persists in the body—may allow for intramuscular injection rather than intravenous infusion, potentially making it more practical for long-term use. The antibody shares a backbone with pemivibart, an Invivyd candidate that received emergency use authorization for COVID-19 prevention in immunocompromised patients, and adintrevimab, which showed clinical benefit in Phase 2/3 trials.
Drs. Amy Proal and David Putrino will present this study design to RECOVER-TLC, the National Institutes of Health initiative tasked with evaluating and funding potential Long COVID treatments, at the Second Annual RECOVER-TLC Workshop in Bethesda, Maryland on September 9-10, 2025. Putrino will present the clinical study design on September 10 at 9:25 a.m. ET; Proal will discuss the broader antiviral landscape and monoclonal antibody therapy's potential role in Long COVID research at 1:00 p.m. ET that same day.
Dr. Michael Peluso, a member of the SPEAR Study Group, emphasized that most Long COVID research to date has not examined at scale whether persistent viral RNA or spike antigen actually drives the disease, or whether monoclonal antibodies can modulate that persistence. "At this point, the time is right and potential best-in-class mAb tools are available," Peluso said, pointing to VYD2311 as a candidate worth testing.
For patients living with Long COVID, the proposal carries weight. Melissa Walker, a Long COVID sufferer, described the disease as having "stolen my ability to function in even the most ordinary parts of life, leaving me disabled and grieving the loss of who I was." She said the SPEAR Study Group's work "gives me hope that there could be a therapy to help our patient community." The condition has left millions unable to work, exercise, or manage basic daily tasks, and no proven treatments exist. If RECOVER-TLC approves funding for this trial and the results support the viral persistence hypothesis, it could reshape how Long COVID is understood and treated—moving from managing symptoms to targeting what researchers believe may be the disease's root cause.
Bemerkenswerte Zitate
Long COVID studies have not explored at scale the critical underlying biology of SARS-CoV-2 RNA or spike antigen persistence, and whether that persistence can be modulated via monoclonal antibodies.— Dr. Michael Peluso, SPEAR Study Group member
Long COVID stole my ability to function in even the most ordinary parts of life, leaving me disabled and grieving the loss of who I was. The work that the SPEAR Study Group is doing gives me hope that there could be a therapy to help our patient community.— Melissa Walker, Long COVID patient
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