Cutting-edge recommendations provide treatment path for millions of long COVID patients

Medford, MA, Feb 11, 2025 — Long COVID, a debilitating condition following SARS-CoV-2 infection, continues to disable tens of millions of people globally, yet no approved treatments exist.

However, Long COVID is not a mystery. Research increasingly links the condition and its symptoms to persistent SARS-CoV-2 infection, with evidence showing that the virus can linger in reservoirs for months, or even years, in at least a subset of individuals. While early efforts are underway to treat these reservoirs, more well-designed clinical trials are desperately needed to treat and ultimately cure the millions suffering from long COVID.

A new Viewpoint published in Lancet Infectious Diseases and supported by PolyBio Research Foundation provides a roadmap for testing interventions aimed at clearing SARS-CoV-2 reservoirs. The report, authored by 36 experts from 20 leading institutions worldwide, details key considerations for trial design, drug candidates, and viral persistence biomarker development.

“I have been sick for four years and I know the science is there,” says long COVID patient Jon Douglas. “This report confirms that we have a plan for the trials that could finally help patients like me recover.”

Drawing on what scientists have learned from other viral infections such as HIV, hepatitis C, and cancer clinical trials, the report outlines several promising approaches to treat long COVID patients with persistent SARS-CoV-2:

• Monoclonal Antibodies (mAbs): mAbs could neutralize the virus or boost the immune system’s ability to eliminate infected cells. Some mAbs are in early trials for long COVID, however many promising candidates remain untested.
• Antivirals: Short-term antiviral trials for long COVID have shown mixed results, but longer treatment durations – similar to those used in hepatitis C – may be necessary.
• Immunotherapies: Restoring effective immune function with therapies like cytokine treatments or immune modulators could improve reservoir clearance.
• Viral RNA Targeting: Novel approaches such as CRISPR-based treatments could potentially deactivate persistent viral RNA, but further validation is needed.
• Combination Trials: Combining therapeutics – such as antivirals together with mAbs or immune system therapies – may be needed to most effectively target viral reservoirs.

“Our approach recognizes the importance of a multifactorial strategy,” says report senior author Michael Peluso MD, an infectious disease researcher at the University of California, San Francisco (UCSF) School of Medicine. “We believe that combining therapies targeting both the virus and the immune system may be the best way forward, especially if dealing with persistent viral reservoirs in immune-protected tissues.”

The report also highlights the urgent need to develop validated biomarkers capable of detecting persistent virus in accessible fluids like blood and saliva—an effort with immense potential to accelerate clinical trials, but one that remains underdeveloped. “Advancing such tests represents a major opportunity for the biotech sector,” says report first author Amy Proal PhD, who serves as President of the PolyBio Research Foundation.

“We know what long COVID clinical trials to run – and we have a plan to do it,” says Peluso. “Now we need everyone on board to collaborate and expand funding and industry support to make it happen. The health of millions is at stake.”

About PolyBio

PolyBio Research Foundation is a 501(c)3 transforming how complex chronic conditions like long COVID are studied, diagnosed, and treated. PolyBio conceptualizes research projects that identify root cause drivers of chronic conditions and builds collaborative teams to make the projects a reality.