Evaluating the safety and efficacy of nirmatrelvir-ritonavir therapy in pregnant women with COVID-19: a systematic review and meta-analysis

Eur J Clin Pharmacol. 2025 Apr;81(4):495-506. doi: 10.1007/s00228-025-03808-8. Epub 2025 Feb 13.

Abstract

Purpose: Pregnant women are at heightened risk for severe COVID-19 outcomes. However, treatment options during pregnancy remain limited due to concerns over their safety and efficacy.

Methods: This systematic review and meta-analysis assessed the safety and efficacy of nirmatrelvir-ritonavir in pregnant women diagnosed with mild-to-moderate COVID-19. The analysis focused on cases where the treatment was initiated within five days of symptom onset. A single-arm meta-analysis was performed to comprehensively evaluate outcomes across maternal, delivery, and neonatal domains.

Results: In line with PRISMA guidelines, six studies involving a total of 427 pregnant patients were included in the analysis. Hospitalization was reported in 2% of patients (95% CI: 1%-5%), with low heterogeneity across studies (I2 = 21.9%). Drug discontinuation and new-onset gestational diabetes (NOGDM) had a pooled estimate of 0.7% (95% CI: 3% to 15%) and 4.0% (95% CI: 1% to 16%), respectively, with substantial heterogeneity (I2 = 64.7% and 66.5%), respectively. New-onset gestational hypertension (NOGHTN) had a pooled estimate of 4% (95% CI: 1% to 26%), with considerable heterogeneity (I2 = 78.81%). For neonatal outcomes, the pooled estimate for birth weight was 3186 g (95% CI: 3123-3248 g; I2 = 0%), and no maternal or neonatal deaths were reported across the included studies.

Conclusion: Nirmatrelvir-ritonavir appears safe and effective for mild-to-moderate COVID-19 in pregnant women, with low rates of hospitalization and adverse maternal outcomes. Larger, randomized studies are crucial to confirm these findings and ensure safety in diverse populations.

Keywords: COVID-19; Fetal; Neonates; Nirmatrelvir-Ritonavir; Pregnancy; SARS-COV2.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Antiviral Agents* / administration & dosage
  • Antiviral Agents* / adverse effects
  • Antiviral Agents* / therapeutic use
  • COVID-19
  • COVID-19 Drug Treatment*
  • Drug Combinations
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Pregnancy
  • Pregnancy Complications, Infectious* / drug therapy
  • Pregnancy Outcome
  • Ritonavir* / administration & dosage
  • Ritonavir* / adverse effects
  • Ritonavir* / therapeutic use
  • SARS-CoV-2
  • Treatment Outcome

Substances

  • Ritonavir
  • Antiviral Agents
  • Drug Combinations