Case series suggests longer nirmatrelvir/ritonavir treatments may benefit some individuals with long COVID, highlighting the need for further research into optimal usage.

Study: Impact of extended-course oral nirmatrelvir/ritonavir in established Long COVID: a case series. Image Credit: Ariya J/Shutterstock.com

In a recent study published in Communications Medicine, researchers examined the impact of an extended course of oral nirmatrelvir/ritonavir (Paxlovid) on long COVID.

Long COVID is a multisystemic illness that occurs after coronavirus disease 2019 (COVID-19). Long COVID symptoms include fatigue, brain fog, autonomic dysfunction, post-exertional malaise (PEM), tinnitus, headache, autonomic dysfunction, palpitations, blurred vision, loss of taste/smell, chronic cough, chest pain, gastrointestinal symptoms, and changes in sexual capacity/desire.

Paxlovid is an oral antiviral that, when administered for acute COVID-19, can decrease viral activity, symptom severity, fatalities, and potentially the odds of long COVID.

Studies have reported symptomatic improvement in long COVID subjects after a five-day Paxlovid course. However, symptom recurrence was observed in some patients post-treatment, suggesting that protracted treatment may be required.

In the present study, researchers described the cases of individuals with long COVID on an extended Paxlovid course. Cases were identified through two methods. First, individuals who shared experiences in public fora for or led by individuals with long COVID were invited. Second, people who heard about the project contacted the study team to share their experiences.

Eligible individuals had a long COVID diagnosis and reported taking Paxlovid for ≥ five days. Only individuals with clinically confirmed COVID-19 or positive test results were included. All patients were evaluated during their long COVID experience by a healthcare provider, who validated that their symptoms were due to long COVID.

Subjects shared preexisting written texts or talked with the authors about their experiences. Participants were allowed to review/edit the written description of their experiences. Participants typically shared their experiences within one month of completing their antiviral course, drawing from notes or medical records.

Overall, 13 individuals with long COVID were enrolled. Eleven individuals took an extended course while negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beyond the acute phase, while two did so while SARS-CoV-2-positive in the context of reinfection.

The first case was a 56-year-old male who developed COVID-19-like symptoms in March 2020 and developed long COVID-19 symptoms in August 2020.

As such, the individual completed a five-day Paxlovid course in September 2022 without changes in symptoms and a 15-day course in December 2022. The subject reported complete symptom resolution one week after the end of the antiviral course. The second case was a 45-year-old female who developed mild COVID-19 in March 2022.

Three weeks after acute infection, the subject developed symptoms of long COVID and was also diagnosed with postural orthostatic tachycardia syndrome and mast cell activation syndrome. In February 2023, the individual started a 15-day Paxlovid course. Two weeks after course completion, the person reported improved physical strength, mental clarity, energy, and complete resolution of orthostatic intolerance symptoms.

The third case was a female aged 25 who developed COVID-19 symptoms in May 2022. The subject’s long COVID symptoms were mainly gastrointestinal, but developed additional symptoms subsequently.

In January 2023, the subject started a 10-day Paxlovid course and experienced a severe crash (on day 4), characterized by increased brain fog, headache, fatigue, light and sound sensitivity, and difficulty walking, balancing, and remaining upright.

The subject recuperated from the initial crash a month later, with PEM and fatigue declining meaningfully. As of July 2023, the subject had been experiencing improvements in some symptoms.

The fourth case was a 51-year-old male with COVID-19 diagnosed in August 2022 and started a five-day Paxlovid course on the day of diagnosis. The subject tested SARS-CoV-2-negative on day 5 but had a symptom relapse and tested positive two/three days after the last antiviral dose.

On day 19, the individual tested negative but still experienced symptoms, and in March 2023, the subject started a 15-day Paxlovid course. The individual regained energy a week later, with reduced PEM, and reported feeling radically better by early June 2023.

The fifth case was an adult female who developed COVID-19-like symptoms in March 2020 and began a 10-day Paxlovid course in June 2023. The subject showed symptomatic improvements within a few days of starting the antiviral course.

The sixth case was a 40-year-old male who developed COVID-19 in March 2020 and had plantar-palmar sensory neuropathies eight weeks after acute infection. The subject completed a five-day Paxlovid course in 2022, achieving near-complete remission by day 3, albeit symptoms progressively relapsed on day 6.

As such, the subject initiated a 30-day Paxlovid course in September 2022. Symptoms improved gradually for the next two months but rebounded in February 2023. The subject tested COVID-19-positive in March 2023, and a 10-day Paxlovid course quickly resolved acute symptoms.

The seventh case was a male aged 27 years who was diagnosed twice with COVID-19 in May and July 2022. Long COVID symptoms appeared three weeks after recovery from the second infection. As such, a 15-day Paxlovid course was started in May 2023. Six days into the treatment, the subject reported a slight improvement, which sustained and improved over time.

The eighth case was a female with clinically confirmed COVID-19 in July 2020, who continued to have symptoms consistent with long COVID after the acute phase. The subject initiated an extended Paxlovid course in April 2023 but did not experience improvements in symptoms.

Similarly, the ninth, tenth, and eleventh cases were all females aged 34–45 who initiated an extended course of Paxlovid for long COVID and had no improvements in symptoms. The twelfth and thirteenth cases started the Paxlovid course within the context of reinfection and, like most others, experienced improvements in long COVID symptoms.

Taken together, the researchers presented a case series of 13 individuals with long COVID who took an extended Paxlovid course; subjects were infected with different SARS-CoV-2 variants, and their treatment lengths varied considerably. Further, there was substantial heterogeneity in the clinical manifestation of long COVID and the impact of Paxlovid on their symptoms.

Notably, only five individuals showed sustained improvements, suggesting that some people may benefit from this antiviral treatment beyond the acute infection phase.

Further studies are needed to investigate the optimal duration of the antiviral course, why and how Paxlovid benefits some individuals, and explore other antivirals as a potential treatment for long COVID.