COVID-19
Aiya Almogaber, PharmD
Researchers are urgently seeking effective treatments for postacute sequelae of SARS-CoV-2 infection (PASC), commonly known as “Long COVID.” Long COVID affects millions globally, causing a wide range of persistent symptoms such as fatigue, brain fog, shortness of breath, body aches, GI issues, and cardiovascular problems. These symptoms can last for months or even years, significantly impacting patients’ quality of life and underscoring the need for effective treatments.
A study published on June 7, 2024, in JAMA aimed to evaluate the effectiveness of the antiviral combination drug nirmatrelvir–ritonavir in alleviating Long COVID symptoms. Conducted at Stanford University from November 2022 to September 2023, the randomized clinical trial involved 155 adults experiencing moderate to severe Long COVID symptoms for 3 months or longer. The participants were divided into two groups: 102 received the antiviral treatment and 53 received a placebo.
Key findings
The primary goal of the STOP-PASC trial was to determine if a 15-day course of nirmatrelvir-ritonavir could reduce the severity of the six key Long COVID symptoms. After 10 weeks, results showed no significant difference between the treatment and placebo groups in terms of symptom severity. Both groups experienced some improvement, but the antiviral treatment did not provide a notable benefit.
The study included 155 participants with a median age of 43 years; 59.4% were female, 40.6% male; and the racial composition was diverse, including 12.9% Asian, 1.9% Black, 12.3% Hispanic, and 74.2% white participants. Most participants had been vaccinated against COVID-19, and 26.5% had previously used antiviral medications for acute COVID-19. All participants reported fatigue at enrollment, with brain fog being the second most common symptom.
Safety was a crucial aspect of the trial. Most participants tolerated the 15-day course of nirmatrelvir-ritonavir well, with adverse events being mostly mild, including taste disturbances and diarrhea. Serious adverse effects were rare and not directly linked to the treatment, reflecting a safety profile consistent with its use in treating acute COVID-19.
Secondary outcomes evaluated individual symptoms over different time points during 15 weeks. The “most bothersome” symptoms reported were fatigue and brain fog. There were no significant differences between the treatment and placebo groups in the severity of these symptoms at 5, 10, and 15 weeks. Other measures, including the Patient-Reported Outcomes Measurement Information System (PROMIS) scales for physical function, fatigue, dyspnea, and cognitive abilities, also showed no significant between-group differences.
Looking forward
The STOP-PASC trial highlights the ongoing challenges in addressing Long COVID. It underscores the necessity for continued research and collaboration to develop effective treatments.
The trial also points to the importance of personalized medicine. Given the diverse symptoms and impacts on patients, a tailored approach to treatment may be more effective than a one-size-fits-all strategy.
While the trial did not find significant benefits from the antiviral treatment, it provided valuable insights into the complexities of treating Long COVID. The research team emphasized the need for ongoing studies to explore different treatment approaches, such as varying durations, combinations of therapies, and targeting specific patient subgroups.
Understanding the underlying mechanisms that drive Long COVID is essential in identifying which treatments might be most effective for different subgroups of patients. Future research may also investigate whether early intervention could yield better results.
Researchers are particularly interested in exploring other potential treatments and therapeutic combinations. For instance, some studies are looking into the role of anti-inflammatory drugs, immunomodulators, and even rehabilitation programs tailored to individual patient needs. ■