# Randomized trial of nirmatrelvir/ritonavir versus placebo for adults with acute COVID-19 to prevent long COVID: PanoramicNOR Trial

## TL;DR

This study tests if Paxlovid can prevent long-term symptoms of COVID-19 in adults with early-stage infection.

## Contribution

The trial introduces a novel approach to prevent long COVID using nirmatrelvir/ritonavir in early-stage patients.

## Key findings

- The trial will assess if Paxlovid reduces persistent symptoms like fatigue, dyspnea, and cognitive issues.
- Results will be evaluated at 3, 6, 12, and 24 months post-treatment.
- The study could provide evidence for a simple oral treatment to mitigate long COVID's public health impact.

## Abstract

The high prevalence of long-term persisting symptoms after COVID-19 (coronavirus disease 2019), termed long COVID or post-COVID-19 condition, even among those with mild initial disease, may have a large public health impact. Apart from avoiding infection, there is no proven prevention or treatment for long COVID. We will perform a randomized placebo-controlled clinical trial to assess whether treatment with the novel antiviral, nirmatrelvir and ritonavir (Paxlovid®) for acute COVID-19 can prevent the development of long COVID.

This is a randomized double-blinded placebo-controlled trial that aims to recruit 2000 nonpregnant persons aged 18 to 64 years with acute COVID-19 with positive PCR and/or antigen test and symptom duration of not more than 5 days. Participants will be randomized 1:1 to a 5-day course of Paxlovid (two tablets 150-mg nirmatrelvir and one tablet 100-mg ritonavir twice daily) or a 5-day course of placebo (similar number of tablets of equal appearance). The primary endpoint will be persistent symptoms compatible with long COVID, assessed as the prevalence of a dichotomous variable corresponding to the presence (1) or absence (0) of one or more of the following symptoms: (i) fatigue, (ii) dyspnea, and (iii) cognitive symptoms (memory and/or concentration problems). The primary outcome will be evaluated at 3-month follow-up and then re-evaluated at 6, 12, and 24 months.

As more than 750 million people with confirmed COVID-19 have survived globally, the potential burden of long COVID on societies is formidable. If a simple 5-day oral treatment course with nirmatrelvir/ritonavir is shown to prevent long COVID, it would be a highly attractive intervention at an individual level and a mitigation of its public health consequences.

ClinicalTrials.gov NCT05852873. Registered on May 2023.

The online version contains supplementary material available at 10.1186/s13063-025-09226-6.