Nirmatrelvir-Ritonavir Ineffective for Long COVID Symptoms

A recent study has revealed that a 15-day regimen of nirmatrelvir-ritonavir (NMV/r), also known as Paxlovid, is safe but does not significantly improve symptoms associated with postacute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as Long COVID. This study, published in JAMA Internal Medicine on June 7, 2024, coincided with the Demystifying Long COVID North American Conference held in Boston from June 6 to 7.

Dr. Linda N. Geng and her team at the Stanford University School of Medicine in California conducted the research to evaluate the effectiveness of NMV/r in alleviating moderate-to-severe PASC symptoms that had persisted for more than three months. The study involved 155 adult participants who were randomly divided in a 2:1 ratio to receive either the NMV/r treatment (300 mg and 100 mg) or a placebo-ritonavir (PBO/r) twice daily.

Notably, nearly all participants (153 out of 155) had completed their primary COVID-19 vaccination series. The average time between their initial SARS-CoV-2 infection and the start of the trial was approximately 17.5 months. After a 10-week period, the researchers found no significant difference in the severity of six core symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal issues, and cardiovascular symptoms) between the group treated with NMV/r and the placebo group.

Furthermore, the study indicated no substantial differences between the two groups in terms of Patient Global Impression of Severity or Change scores, cumulative symptom scores, or changes from baseline to 10 weeks in various aspects like fatigue, dyspnea, cognitive function, and physical function, as measured by the Patient-Reported Outcomes Measurement Information System. Adverse events were generally mild and occurred at similar rates in both groups.

Dr. Upinder Singh, a senior author also from Stanford University, commented on the rationale behind the study. "There are some hypotheses suggesting that residual viral particles and molecular debris could be causing the prolonged symptoms in some Long COVID patients. We thought if this were true, then Paxlovid might help alleviate these symptoms," Dr. Singh explained.

Despite the lack of significant symptomatic improvement, the study provides valuable insights into the ongoing quest to understand and treat Long COVID better. It also underscores the importance of continued research and clinical trials to find effective treatments for those suffering from persistent post-COVID symptoms.

This study was financially supported by Pfizer, the pharmaceutical company that manufactures nirmatrelvir-ritonavir (Paxlovid).