Publication
Nirmatrelvir–Ritonavir and Viral Load Rebound in Covid-19
Editorial/Letter published in NEJM Published September 2022.
What is it about?
This study tested nirmatrelvir/ritonavir (Paxlovid), an antiviral pill for adults with COVID-19 who were unvaccinated, not in hospital, but at high risk of becoming seriously ill. It was a randomised, double-blind, placebo-controlled clinical trial - the gold standard for testing medicines.
Over 2,100 adults in 20 countries took part. Everyone started treatment within five days of developing symptoms and received either Paxlovid or a placebo for five days. Researchers looked at how the drug affected recovery time, hospitalisations, and deaths.
People who took Paxlovid had an 89% lower risk of hospitalisation or death when started within three days of symptoms (0.7% vs 6.5% for placebo). It also helped people recover faster - symptoms improved two to three days sooner on average.
Side effects were mostly mild and similar between groups, including headache, mild stomach upset, and a slightly altered taste.
Why is it important?
COVID-19 remains a threat, especially for people with conditions that raise the risk of severe illness. While vaccines reduce risk, not everyone responds equally well to them¹. For these patients, treatments that can prevent progression of the infection at an early stage are essential.
This study shows that Paxlovid not only prevents hospitalisation and death but also helps people recover faster, meaning less time feeling unwell and less strain on healthcare systems. Because it’s a five-day oral treatment, it can be taken at home and started soon after symptoms appear, making it highly practical.
The results also confirm that Paxlovid is generally safe and well-tolerated, with most side effects mild and temporary. This balance of strong protection and good tolerability has made Paxlovid a key treatment option for people at high risk of progression to severe COVID-19, especially during early infection when the drug works best.
Key takeaways: 1. Randomised, double-blind, placebo-controlled study showed strong evidence that Paxlovid works safely in patients with high risk of progression to severe COVID-19.
2. Paxlovid reduced hospitalisation or death by 89% when started within three days of symptoms (0.7% vs 6.5%).
3. Patients recovered two to three days faster and needed fewer medical visits than those taking placebo.
4. Side effects were mild and similar to placebo, mainly mild stomach upset, headache, or taste changes.
5. Paxlovid offers a safe, convenient oral treatment that protects high-risk patients and helps ease pressure on hospitals.
References
¹ Immune Response to COVID‑19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review: Napuri NI, Curcio D, Swerdlow DL, et al. Infectious Diseases and Therapy. 2022.
This review explicitly shows that immunocompromised patients have substantially reduced immune responses to COVID‑19 vaccination, even with mRNA vaccines. The authors emphasize that this population remains vulnerable despite vaccination, underscoring the need for additional protective strategies, including early therapeutic interventions when infection occurs.
EM-GLB-CVD-0020 | April 2026 Page published: 01-May-2026
