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

Clin Infect Dis. 2023 Feb 8;76(3):e342-e349. doi: 10.1093/cid/ciac443.


Background: Paxlovid was granted an Emergency Use Authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19), based on the interim analysis of the Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real-world data to evaluate the effectiveness of Paxlovid.

Methods: The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first-ever positive test for severe acute respiratory syndrome coronavirus 2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28-day hazard ratio (HR) for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable.

Results: Overall, 180 351 eligible patients were included; of these, only 4737 (2.6%) were treated with Paxlovid, and 135 482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HRs of 0.54 (95% confidence interval [CI], .39-.75) and 0.20 (95% CI, .17-.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction P < .05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status.

Conclusions: This study suggests that in the era of Omicron and in real-life settings, Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.

Keywords: COVID-19; Paxlovid; SARS-CoV-2; nirmatrelvir/ritonavir; vaccine.

MeSH terms

  • Adult
  • Aged
  • COVID-19 Vaccines
  • COVID-19*
  • Cardiovascular Diseases*
  • Humans
  • SARS-CoV-2


  • nirmatrelvir and ritonavir drug combination
  • COVID-19 Vaccines