Objective:

To evaluate the effectiveness of nirmatrelvir–ritonavir in reducing severe COVID-19 outcomes across diverse age groups and vaccination statuses in Taiwan.

Key Findings:

• Nirmatrelvir–ritonavir treatment was associated with a significantly lower risk of hospitalization (HR 0.32), ICU admission (HR 0.41), invasive ventilatory support (HR 0.38), and death (HR 0.42).
• The composite outcome of hospital admission or death was also significantly reduced (HR 0.34).
• Effectiveness was consistent across age and vaccination status subgroups, with the greatest benefit in unvaccinated individuals and those aged ≥65 with additional risk factors.

Interpretation:

Outpatient use of nirmatrelvir–ritonavir significantly lowers the risk of severe COVID-19 outcomes, highlighting its clinical value, especially in vulnerable populations.

Limitations:

• Observational study design may introduce confounding factors.
• Data may not capture all variables influencing treatment outcomes.

Conclusion:

Nirmatrelvir–ritonavir is effective in reducing severe COVID-19 outcomes, reinforcing the importance of early antiviral treatment, particularly for aging and unvaccinated populations.