Short- and long-term comparative effectiveness of nirmatrelvir/ritonavir and molnupiravir in asthma patients: a cohort study

Respir Res. 2025 Feb 28;26(1):75. doi: 10.1186/s12931-025-03156-2.

Abstract

Background: Few studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.

Methods: This is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication. Outcomes included acute and post-acute mortality, post-acute all-cause hospitalization, and cause-specific hospitalization.

Results: 1,745 patients were eligible for this study, with a median follow-up time of 365 days (IQR: 335-365). Patients in the nirmatrelvir/ritonavir group had significantly lower risks of acute inpatient death (HR, 0·27 [95% CI, 0·12 to 0·59]; p = 0·0011), post-acute inpatient death (HR, 0·49 [95% CI, 0·28 to 0·85]; p = 0·011), all-cause hospitalization (HR, 0·72 [95% CI, 0·58 to 0·89]; p = 0·0020), and myocardial infarction (HR, 0·10 [95% CI, 0·01 to 0·92]; p = 0·042) than patients in the control group. The risk of all-cause hospitalization was significantly lower in the nirmatrelvir/ritonavir group compared to the molnupiravir group (HR, 0·65 [95% CI, 0·52 to 0·81]; p = 0·00012). Among patients who were prescribed medium-/ high-dose inhaled corticosteroids, the nirmatrelvir/ritonavir group had a lower hazard of asthma exacerbation than the molnupiravir group (HR, 0·58 [95% CI, 0·35 to 0·95]; p = 0.030).

Conclusion: Compared with molnupiravir, nirmatrelvir/ritonavir may offer more benefits in reducing the risk of post-acute sequelae of COVID-19 among asthma patients. In addition, the post-acute benefits of the antivirals were also demonstrated in patients with mild asthma, which have not been generally recommended in existing clinical management guidelines.

Keywords: Asthma; COVID-19; Effectiveness; Molnupiravir; Nirmatrelvir/ritonavir.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • Asthma* / diagnosis
  • Asthma* / drug therapy
  • Asthma* / epidemiology
  • COVID-19 Drug Treatment*
  • Cohort Studies
  • Cytidine / analogs & derivatives
  • Cytidine / therapeutic use
  • Female
  • Hong Kong / epidemiology
  • Hospitalization
  • Humans
  • Hydroxylamines / therapeutic use
  • Leucine / analogs & derivatives
  • Leucine / therapeutic use
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Proline / therapeutic use
  • Retrospective Studies
  • Ritonavir* / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • molnupiravir
  • Ritonavir
  • Antiviral Agents
  • Hydroxylamines
  • Cytidine
  • Leucine
  • Proline