A major new study from researchers at the University of California, San Francisco has found that Pfizer’s antiviral COVID-19 treatment Paxlovid does not reduce the risk of patients developing long COVID. The findings raise questions about the ability of current treatments to prevent long-term COVID complications.
Key Details from the UCSF Study
The study, published January 4th in JAMA Network Open, analyzed records from over 56,000 patients who had tested positive for COVID-19. Some patients received Paxlovid after their diagnosis, while others did not take the antiviral.
After adjusting for other risk factors, the researchers found no significant difference in the rates of most long COVID symptoms between the Paxlovid and non-Paxlovid groups after 30, 60, or 90 days.
Symptoms analyzed included fatigue, brain fog, muscle pain, headache, anxiety, and more. The only exception was that Paxlovid takers had a slightly lower incidence of cough and shortness of breath at 90 days.
“We interpret these data to mean that while antiviral therapies reduce acute phase viral load in SARS-CoV-2 infection, this therapy alone does not prevent post-acute sequalae either by preventing viral persistence or through immune modulation,” the authors wrote.
They noted the need for more research into what causes long COVID and how to prevent it.
Importance for Long COVID Prevention
The findings contradict earlier hopes that antiviral treatments like Paxlovid, by reducing initial viral load, could lower the risk of prolonged symptoms.
“We had expected that Paxlovid would reduce new incidents of long COVID, so we were surprised when we looked at the data and it was really no different than people who didn’t get treated,” said senior author Michael Peluso in an interview.
Long COVID has affected up to 30% of COVID survivors in past studies, causing disability for some.
“Long COVID is a huge issue,” said Eric Topol, founder of the Scripps Research Translational Institute, on Twitter. “So now we know that antiviral therapy, as effective as Paxlovid is, doesn’t mitigate long COVID risk.”
|Long COVID Risk Compared to Untreated
Without Paxlovid seemingly able to prevent long COVID, the search continues for ways to address the growing issue.
Lingering Questions Around Rebound
In addition to long COVID prevention, there have been questions around whether Paxlovid could contribute to COVID recurrence after treatment.
Some patients have experienced rebounds in symptoms or viral load after completing a Paxlovid course, which lasts 5 days. But the new UCSF research found that rebounds were no more common in the Paxlovid group compared to the untreated group.
“Our findings suggest rebound is not unique to treated patients and not a result of Paxlovid therapy per se,” the authors stated.
Still, rebounds do occur and are not yet fully explained. It remains unclear if tweaks to the Paxlovid regimen could help prevent them.
Access and Awareness Challenges
While Paxlovid does not appear to impact long COVID risk, its ability to cut hospitalization rates still makes it an important tool. However, many patients who could benefit from the drug face barriers in access or lack awareness it exists.
A November 2022 study found that around a quarter of high-risk patients were not offered Paxlovid despite eligibility. Barriers included costs, geographic distance from pharmacies, and physicians lacking information on antiviral options.
Narrow prescription time windows also constrain Paxlovid’s reach. It must be taken within 5 days of symptom onset to be effective. Many patients do not seek care or receive test results fast enough for doctors to prescribe in time.
“Too many people who could have benefited from this treatment have not received it,” said White House COVID-19 Response Coordinator Dr. Ashish Jha.
Jha encouraged optimizing awareness and availability to “make sure that it gets to everyone who needs it.”
What Comes Next?
While current antivirals like Paxlovid appear ineffective at reducing long COVID risks, researchers will continue investigating alternative treatments in clinical trials. Potential options scientists are exploring include:
- Anti-inflammatory drugs to quell severe immune reactions
- Medications targeting residual viruses or autoantibodies
- Neurological treatments for cognitive issues
- Physical rehabilitation programs
“We have to keep looking for long COVID solutions,” said immunologist Akiko Iwasaki. “[Paxlovid] helps acute disease but doesn’t prevent long COVID. We need specifically designed trials to prevent long COVID.” She suggested starting trials of drugs as pre-exposure prophylaxis before initial infections.
Better understanding root causes of prolonged symptoms also remains a priority. Some leading theories implicate tissue damage from inflammation, lingering virus reservoirs, or autoantibodies attacking the body’s own tissues.
“We have to get to the bottom of what is driving these ongoing symptoms,” said Peluso, “Because unless we understand what the mechanism is, it will be very hard to identify effective therapies.”
Uncovering these mechanisms could unlock new treatments and preventions for long COVID in 2024 and beyond. But for now, the condition remains mysterious, unpredictable and incurable for millions.
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