Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series, 2025, Cohen

https://www.nature.com/articles/s43856-024-00668-8

• Article
• Open access
• Published: 06 January 2025

Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series

• Alison K. Cohen,
• Toni Wall Jaudon,
• Eric M. Schurman,
• Lisa Kava,
• Julia Moore Vogel,
• Julia Haas-Godsil,
• Daniel Lewis,
• Samantha Crausman,
• Kate Leslie,
• Siobhan Christine Bligh,
• Gillian Lizars,
• JD Davids,
• Saniya Sran,
• Michael Peluso &
• Lisa McCorkell

Communications Medicine volume 4, Article number: 261 (2024) Cite this article

Abstract

Background
Prior case series suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) benefits some people with Long COVID, within and/or outside of the context of an acute reinfection. To the best of our knowledge, there have been no prior case series of people with Long COVID who have attempted longer courses of nirmatrelvir/ritonavir.

Methods
We documented a case series of 13 individuals with Long COVID who initiated extended courses (>5 days; range: 7.5–30 days) of oral nirmatrelvir/ritonavir outside (n = 11) of and within (n = 2) the context of an acute SARS-CoV-2 infection. Participants reported on symptoms and health experiences before, during, and after their use of nirmatrelvir/ritonavir.

Results
Among those who take an extended course of nirmatrelvir/ritonavir outside of the context of an acute infection, some experience a meaningful reduction in symptoms, although not all benefits persist. Others experience no effect on symptoms. One participant stopped early due to intense stomach pain. For the two participants who took an extended course of nirmatrelvir/ritonavir within the context of an acute reinfection, both report eventually returning to their pre-re-infection baseline.

Conclusions
Extended courses of nirmatrelvir/ritonavir may have meaningful benefits for some people with Long COVID but not others. We encourage researchers to study how and why nirmatrelvir/ritonavir benefits some and what course length is most effective, with the goal of informing clinical recommendations for using nirmatrelvir/ritonavir and/or other antivirals as a potential treatment for Long COVID.

 

Plain language summary

Long COVID is an infection-associated chronic condition in which symptoms persist more than 12 weeks after an acute COVID-19 infection.

Prior reports suggest that a 5-day course of oral Paxlovid (nirmatrelvir/ritonavir) may help some people with Long COVID, but there have not yet been any reports of people with Long COVID trying extended courses of nirmatrelvir/ritonavir.

Our patient-led study documents the experiences of 13 people with Long COVID who tried extended courses of Paxlovid; some were in the midst of a reinfection and others were not.

Some participants reported meaningful benefits, although not all improvements lasted long-term.

Others experienced no changes in symptoms.

Our results suggest that extended courses of nirmatrelvir/ritonavir could be beneficial for some people with Long COVID.

 

https://www.eurekalert.org/news-releases/1069265

News Release 6-Jan-2025
Extended Paxlovid may help some people with long COVID
Peer-Reviewed Publication

University of California - San Francisco



An up-close look at how patients respond to the drug at different times and doses adds nuance to a recent finding that Paxlovid does not work for long Covid.

An extended course of Paxlovid appears to help some patients with long Covid, according to a case series by UC San Francisco researchers that suggests this treatment option holds promise for some of those struggling with debilitating symptoms.

These results are at odds with recent research that has failed to show the antiviral can alleviate persistent symptoms of the disease. The authors said more study is needed to find out which patients may benefit from the drug and how long it should be given.

The Centers for Disease Control and Prevention (CDC) estimates that 17.6 million Americans, or 1 in 13 adults, have long Covid. These individuals experience symptoms for months or even years after their initial Covid-19 infection that range from brain fog and headaches to respiratory and cardiovascular issues.

“We are about five years into the pandemic, and yet there are not yet any federally-approved treatments for long Covid,” said Alison Cohen, PhD, MPH, an assistant professor of epidemiology and biostatistics at UCSF and first author of the paper. “This is not a silver bullet, but it may help a lot of people in a meaningful way.”

The study appears Jan. 6 in the Nature publication Communications Medicine.

Interviews with patients reveal the drug helps some

In June, a randomized controlled clinical trial of a 15-day course of nirmatrelvir/ritonavir, the drug combination marketed as Paxlovid, concluded that it was safe, although it did not lessen long Covid symptoms. The researchers noted that further research may show benefits for people with specific symptoms or at different doses.

The UCSF team collaborated with long Covid patients, some of whom are members of the Patient-Led Research Collaborative, a group of people with long Covid and other associated chronic conditions who are also researchers. The researchers took a closer look at what happened when people took a longer course of Paxlovid to see if it might work in people with specific symptoms or at different times in their disease. They also examined the experiences of people who contracted different strains of SARS-CoV-2. They found that five of the 13 patients in the study experienced sustained improvements in their symptoms. Others experienced temporary reprieves; and some had no improvement. Treatment lengths varied, but many took Paxlovid for 15 days.

For example, a 56-year-old man who developed long Covid at the start of the pandemic was plagued for more than two years with fatigue, headaches, photosensitivity, brain fog, exercise intolerance, elevated heart rate and joint pain. He took Paxlovid for five days in September of 2022 with no change in his symptoms. Three months later, he took it for 15 days and reported that both his cognitive and his physical symptoms improved.

And a 45-year-old woman who developed long Covid in January of 2022 experienced fatigue, breathing difficulties, chest pain, weight loss and migraines for months after her infection. A five-day course of Paxlovid in October of 2022 gave her a three-day reprieve from her symptoms. But when she took a 15-day course the following month, it did not affect her symptoms at all.

With more than 200 symptoms ascribed to the condition, long Covid has remained difficult to define, diagnose or treat. Researchers are still trying to understand the biological mechanisms that underlie the disorder; and UCSF has launched the world’s first long Covid tissue bank.

“If we’ve learned one thing over the last four years, it’s that long Covid is complex, and figuring out why some people benefit so remarkably from antiviral treatment while others don’t is one of the most important questions for the field,” said study co-author Michael Peluso, MD, principal investigator of the UCSF long COVID research program and an infectious disease researcher in the UCSF School of Medicine. “We are going to need to embrace that complexity to get answers for the millions of people suffering from this condition.”

Authors: Additional co-authors are associated with the Patient-Led Research Collaborative, a group of long Covid patients and individuals with associated illnesses who are also researchers.

Funding: The authors received no funding for this work.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu, or see our Fact Sheet.
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Journal
Communications Medicine

 

Statements like this make me inclined to assume the authors are not sufficiently committed to scientific rigour to take any notice of. (I was moving in that direction anyway.)

These are not benefits.
They are improvements. Nothing in a series like this indicates that there is any causal link to a treatment. If researchers haven't got that into their heads it is likely that their lab findings are similarly subject to not knowing how to produce reliable data.