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

Abstract

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.

Figure 1.

Flowchart for selection of study population. *Any of the following: age ≥60 years, body mass index ≥30 kg/m², diabetes, hypertension, cardiovascular disease, chronic liver disease, chronic lung disease, chronic kidney disease, neurological disease, immunosuppression, and malignancy. Abbreviations: COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2.

Multivariable odds ratios for risk factors associated with starting Paxlovid treatment within 5 days after positive test for severe acute respiratory syndrome coronavirus 2 (n = 211 279). *The following variables were included in the multivariable logistic regression model, using backward selection: age, sex, population sector, socioeconomic status, body mass index, diabetes, hypertension, cardiovascular disease, chronic liver disease, chronic lung disease, chronic kidney disease, neurological disease, malignancy in the prior year, immunosuppression, and adequate coronavirus disease 2019 vaccination. Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019.

Figure 3.

The effectiveness of Paxlovid in reducing the risk of severe coronavirus disease 2019 or mortality by subgroups of selected sociodemographic and clinical variables. *Selection of examined subgroups was based on variables that were retained in the multivariable Cox hazard regression analysis of the overall effect (Table 2). Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019.