In what will be a blow for millions of people with long Covid, which currently has no approved treatment or cure, a recent study found that taking the antiviral drug Paxlovid does not improve symptoms any better than a placebo.
Paxlovid has long been a source of hope for those with long Covid, which scientists have hypothesised as viral material that lingers in the body, potentially causing long-lasting symptoms including fatigue, the inability to exercise, brain fog, and more.
A drug like Paxlovid, which stops the virus from multiplying and reduces the amount of it in the body, seemed to many like a promising treatment.
But the study, published in JAMA Internal Medicine, found that although taking Paxlovid for 15 days was safe, it did not improve key long Covid symptoms better than a placebo, reports TIME Magazine.
“I would have loved to bring forward a paper that said, ‘Great benefit’,” said senior author Dr Upinder Singh, a professor of infectious diseases at Stanford University.
Even though that wasn’t the result, she added, the study will contribute to scientists’ collective understanding of Paxlovid and long Covid, and does not rule out the possibility of more positive results in the future.
For the trial, Singh and her colleagues enrolled 155 adults with long Covid, all of whom had previously tested positive for Covid-19, lived with long Covid symptoms for at least 90 days, and currently experienced at least two of six major symptoms: fatigue, brain fog, body aches, cardiovascular issues, shortness of breath, and gastrointestinal issues.
Most participants had been sick for longer than a year and almost all had been vaccinated against Covid-19. Three-quarters were white and about 60% were female.
About 100 people were randomly assigned to receive the full Paxlovid regimen, which consists of two medications: the antiviral nirmatrelvir and ritonavir, which prevents nirmatrelvir from breaking down too quickly.
The rest of the group took a placebo with ritonavir, which doesn't work against the SARS-CoV-2 virus on its own. Ritonavir enhanced the placebo because it’s linked to a telltale side effect of Paxlovid – a bad aftertaste – so participants couldn’t necessarily guess whether they’d received the active treatment or not.
Both groups took their drugs twice a day for 15 days, three times longer than patients are currently prescribed Paxlovid. They were then tracked for 15 weeks to assess safety and look for differences in symptoms over time.
On the plus side, the researchers concluded that it’s generally safe to take Paxlovid for 15 days, although non-life-threatening side effects like diarrhoea and bad aftertaste were common. That’s important to know, because some experts believe taking the drug for longer could help prevent outcomes like Paxlovid “rebound”.
A longer course may also be more effective for some high-risk patients, Singh said
But they didn’t find an obvious benefit to taking Paxlovid for symptom relief, she added, and those in the Paxlovid group didn’t fare significantly better than those taking the placebo.
That said, people in both groups saw improvements in their symptom severity over the course of the study. Symptoms often get better over time, Singh said, but participants may also have had some expectation of feeling better simply because they were enrolled in a clinical trial.
And despite the relative improvement, moderate and severe symptoms were still common at the end of the study, which underscores the need for more research on treatments.
Whether Paxlovid, or another antiviral drug, ends up being a viable treatment remains to be seen. While the results from this study aren’t encouraging, other teams are also studying Paxlovid’s efficacy as a long Covid treatment.
It’s possible the drug could work better when taken for a longer length of time, among certain groups of patients, or among those who haven’t been sick as long as the participants in the current study, Singh said.
Another outstanding question: can taking Paxlovid during a case of Covid-19 help prevent long Covid from ever developing?
Some data suggest it may, but other studies have found that it doesn’t work as a preventive measure.
This latest study didn’t address that possibility, and more research is needed before anyone should take Paxlovid for that reason alone, Singh said.
Study details
Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 InfectionThe STOP-PASC Randomised Clinical Trial
Linda Geng, Hector Bonilla, Upinder Singh et al.
Published in JAMA Internal Medicine on 7 June 2024
Abstract
Importance
There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).
Objective
To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms.
Design, Setting, and Participants
This was a 15-week blinded, placebo-controlled, randomised clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration.
Interventions
Participants were randomised 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.
Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.
Results
Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomised to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomisation was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade.
Conclusions and Relevance
The results of this randomised clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.
TIME article – Paxlovid Might Not Be the Long COVID Cure We Hoped For (Open access)
See more from MedicalBrief archives:
Scientists find Paxlovid does not shorten Covid symptoms in fully jabbed
UK regulatory body warns about Paxlovid risks
Paxlovid as a treatment for long Covid