Does Paxlovid (nirmatrelvir/ritonavir) decrease the risk of developing post-acute coronavirus disease (COVID-19) symptoms?

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Last updated: May 28, 2025View editorial policy

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From the Guidelines

Paxlovid is likely to decrease the risk of developing long COVID symptoms, with a notable study suggesting a 25% reduction in the incidence of long COVID. This is based on a recent study published in 2023 in Nature Reviews Microbiology 1, which investigated various treatments for long COVID, including Paxlovid. The study found that Paxlovid, an antiviral medication, showed promise in preventing and treating long COVID.

Key Findings

  • A case report noted resolution of long COVID following treatment with Paxlovid, indicating its potential effectiveness in treating the condition 1.
  • A study investigating the treatment of acute COVID-19 with Paxlovid showed a 25% reduction in the incidence of long COVID, suggesting its potential in preventing long COVID 1.
  • Paxlovid works by inhibiting viral replication early in infection, potentially preventing the widespread inflammation and immune dysregulation thought to contribute to long COVID.

Treatment Considerations

  • The standard treatment course for Paxlovid is 300mg nirmatrelvir (two 150mg tablets) with 100mg ritonavir (one tablet) taken together twice daily for 5 days.
  • Patients typically need to be at higher risk for severe COVID-19 and within the 5-day window from symptom onset to be eligible for Paxlovid treatment.
  • Important considerations include potential drug interactions, as ritonavir affects the metabolism of many medications, and dose adjustments for those with kidney impairment.

Overall Recommendation

Given the current evidence, Paxlovid is a promising treatment option for reducing the risk of developing long COVID symptoms, and its potential benefits should be weighed against potential risks and interactions in clinical practice 1.

From the Research

Paxlovid and Long COVID Symptoms

  • The relationship between Paxlovid treatment and the development of long COVID symptoms is complex and has been investigated in several studies 2, 3, 4, 5, 6.
  • A study published in 2025 found that nirmatrelvir-ritonavir (Paxlovid) did not significantly improve health outcomes in participants with long COVID compared to placebo-ritonavir at day 28 5.
  • However, another study published in 2024 found that Paxlovid treatment during acute COVID-19 had a protective effect on cognitive and fatigue symptom clusters, suggesting that the etiology of these symptoms may be more closely related to viral load than that of respiratory symptoms 6.
  • The same study found that Paxlovid treatment did not have a significant effect on overall PASC incidence, but the results suggest that Paxlovid may have a beneficial effect on certain symptom clusters 6.

Mechanism of Action

  • Paxlovid, which consists of nirmatrelvir and ritonavir, targets the SARS-CoV-2 main protease and inhibits proteolytic cleavage of viral polyproteins during replication, preventing efficient virus production 3, 4.
  • The mechanism of action of Paxlovid suggests that it may be effective in reducing the risk of severe COVID-19 and mortality, but its effect on long COVID symptoms is still being investigated 2, 3, 4.

Clinical Evidence

  • Clinical trials have shown that Paxlovid is effective in reducing the risk of severe COVID-19 and mortality in high-risk patients 2, 3, 4.
  • However, the evidence for the effectiveness of Paxlovid in preventing or treating long COVID symptoms is limited and inconclusive 5, 6.
  • Further studies are needed to fully understand the relationship between Paxlovid treatment and the development of long COVID symptoms 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Effectiveness of Paxlovid in Reducing Severe Coronavirus Disease 2019 and Mortality in High-Risk Patients.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Research

Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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