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Palo Alto/California – The attempt to alleviate the symptoms of Long COVID with the antiviral drug Nirmatrelvir (plus ritonavir), which is approved for the treatment of acute disease, has failed in a phase 2 study. Treatment over 15 days has proven to be safe. According to the JAMA Internal Medicine However, according to the results published (2024; DOI: 10.1001/jamainternmed.2024.2007), patients did not recover faster than a placebo group.

The protease inhibitor nirmatrelvir – in combination with ritonavir, which slows down the breakdown of nirmatrelvir and thus increases its effect – can prevent the development of severe COVID-19 in the early phase of an infection with SARS-CoV-2. Nirmatrelvir/ritonavir has been approved in the USA and Europe as Paxlovid since December 2021/January 2022. Treatment is usually given over 5 days.

About 10 to 20% of all patients recover only slowly after a (severe) illness with COVID-19. If symptoms persist for at least 3 months or new symptoms appear, post-acute COVID-19 syndrome (PASC) or long COVID is diagnosed. The cause is unknown. Persistence of SARS-CoV-2 is currently one of the working hypotheses. It is based on the persistent detection of viral RNA in the upper respiratory tract and stool in some, but by no means all, patients.

Doctors at Stanford University in Palo Alto tested this hypothesis in a clinical study involving 155 patients with PASC with a median age of 43 years. The acute illness with COVID-19 occurred on average 17.5 months ago, and one in four (26.5%) had already been treated with nirmatrelvir/ritonavir at that time. All but two patients had been vaccinated at least once.

All patients complained of at least 2 of the 6 most common “core” symptoms of Long COVID: fatigue, cognitive impairment (“brain fog”), shortness of breath, aching limbs, and cardiovascular or gastrointestinal symptoms.

Patients were treated with either nirmatrelvir/ritonavir or placebo/ritonavir alone for 15 days. Ritonavir was combined with placebo so that patients could not tell which group they were in by the metallic taste.

Ten weeks later, the patients were asked about their symptoms. As Linda Geng from Stanford Medicine and colleagues report, there was a reduction in the 6 PASC symptoms in both groups during this time. However, this was somewhat greater in the placebo group than after treatment with nirmatrelvir. However, the differences were not statistically significant.

The study therefore does not provide any arguments for treatment with Paxlovid, even though the treatment was proven to be well tolerated over 15 days. However, the improvement in symptoms in both groups is a good sign for the long-term prognosis of patients with Long COVID. Most patients gradually recover from the long-term effects of SARS-CoV-2 infection even without treatment. © rme/aerzteblatt.de