An in-depth exploration of recent research has brought fresh perspectives on how patients with long COVID respond to different doses and durations of Paxlovid treatment. Despite earlier findings suggesting the antiviral drug might not effectively address persistent symptoms of long COVID, a detailed case series conducted by researchers at UC San Francisco highlights its potential for some individuals facing chronic challenges from the condition.
This research offers a nuanced view that underscores the importance of individualized treatment approaches. With more than 17.6 million Americans, approximately 1 in 13 adults, estimated by the CDC to suffer from long COVID, the stakes are high in the ongoing effort to understand and alleviate this complex condition. Long COVID encompasses a broad spectrum of symptoms, including cognitive issues like brain fog, physical fatigue, respiratory problems, cardiovascular concerns, and persistent pain, often lasting months or even years after the initial infection. Yet, despite its prevalence and the toll it exacts, there are no federally approved treatments specifically targeting long COVID.
Dr. Alison Cohen, an assistant professor of epidemiology and biostatistics at UCSF and the study’s first author, emphasizes the critical gap in long COVID treatment options. “We are about five years into the pandemic, and yet there are not yet any federally approved treatments for long COVID,” she notes. “This is not a silver bullet, but it may help a lot of people in a meaningful way.” The findings were published in the journal Communications Medicine, presenting fresh hope and setting the stage for future research.
Earlier randomized clinical trials had not demonstrated significant improvement in long COVID symptoms after a 15-day course of Paxlovid, a combination of the antiviral drugs nirmatrelvir and ritonavir. However, these studies acknowledged that certain patient groups or modified treatment protocols might show different results. The UCSF study delved deeper, engaging directly with long COVID patients to document their experiences and better understand the potential therapeutic benefits of extended treatment courses.
The study’s collaborative nature was a hallmark of its approach, involving both clinical researchers and members of the Patient-Led Research Collaborative, an advocacy and research group comprising people with long COVID and related chronic illnesses. This patient-centered research model is uniquely positioned to shed light on the nuanced experiences of those living with the condition. By examining a range of patient cases, the UCSF team aimed to parse out whether variations in timing, dosing, or symptom profiles could influence treatment outcomes.
The study documented the experiences of 13 patients with long COVID, uncovering a spectrum of responses to Paxlovid. Five patients reported sustained improvements in their symptoms, a handful experienced temporary relief, and others noted no improvement. While treatment regimens varied, many participants followed the 15-day course of the antiviral. This heterogeneity in responses underscores the complexity of long COVID and points to the need for highly tailored therapeutic strategies.
One example involved a 56-year-old man who had battled debilitating long COVID symptoms since the early days of the pandemic. Despite dealing with issues like severe fatigue, brain fog, joint pain, and a heightened heart rate for more than two years, a five-day course of Paxlovid initially failed to make any difference. However, a subsequent 15-day course delivered noticeable improvements in his cognitive and physical symptoms, highlighting the importance of revisiting and adjusting treatment durations.
In contrast, a 45-year-old woman developed long COVID after a January 2022 infection, presenting symptoms including migraines, chest pain, and severe fatigue. A five-day Paxlovid regimen brought her short-term relief for three days, but a longer course a month later had no measurable effect. These divergent outcomes illustrate how the same treatment can yield vastly different results depending on individual patient profiles and potentially the strain of SARS-CoV-2 they were exposed to.
Long COVID remains an enigmatic condition, with over 200 symptoms attributed to it, making it difficult to diagnose and treat comprehensively. Researchers are still trying to pinpoint the biological mechanisms driving the disorder, with theories ranging from immune system dysfunction to lingering viral presence. To better understand the condition, UCSF has established the world’s first long COVID tissue bank, a resource expected to yield critical insights in the coming years.
Michael Peluso, MD, an infectious disease researcher and principal investigator of UCSF’s long COVID research program, highlights the complexity of the challenge ahead. “If we’ve learned one thing over the last four years, it’s that long COVID is complex,” Peluso stated. “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.” He underscores the need for an adaptive research approach to meet the diverse needs of long COVID sufferers.
While the UCSF findings do not provide a definitive cure or treatment protocol for long COVID, they emphasize the importance of individualized care and the potential role of antiviral therapy for specific subsets of patients. The research also raises broader questions about how the medical community evaluates treatment success for multifaceted conditions like long COVID, where one-size-fits-all solutions may fall short.
Ultimately, this case series illustrates the need for continued investment in long COVID research to address the condition’s many dimensions. It also underscores the value of patient partnerships in advancing science. As researchers strive to understand who benefits most from therapies like Paxlovid and why, millions of individuals living with long COVID await the development of more effective and accessible treatments. The promise of individualized care, guided by nuanced research, offers a path toward meaningful progress in addressing one of the pandemic’s most persistent and challenging legacies.
Reference: Communications Medicine (2025). DOI: 10.1038/s43856-024-00668-8.https://www.nature.com/articles/s43856-024-00668-8
