On December 21, 2021, the U.S. Food and Drug Administration issued emergency use authorization for the first oral medication, Paxlovid (nirmatrelvir–ritonavir), for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19).1 Although trials have not specifically evaluated the efficacy of nirmatrelvir–ritonavir in pregnancy, nirmatrelvir–ritonavir reduced the risk of hospitalization and death when treatment was initiated within 5 days of symptom onset.2 Furthermore, nirmatrelvir–ritonavir, unlike many monoclonal antibody treatments, has been claimed to be effective against the Omicron variant, the most recent dominant variant.3 The purpose of this case series was to assess short-term outcomes of nirmatrelvir–ritonavir treatment in pregnant patients with mild-to-moderate COVID-19.
This is a descriptive study of pregnant patients who received nirmatrelvir–ritonavir therapy from April 16, 2022 (when the therapy was first prescribed in our practice setting), through May 18, 2022. Patients were eligible to receive nirmatrelvir–ritonavir if they were diagnosed with mild-to-moderate COVID-19 (based on positive results on nasopharyngeal polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), had symptom onset in the previous 5 days, were not requiring oxygen therapy, otherwise did not meet criteria for hospital admission, and had no contraindications to nirmatrelvir–ritonavir. Both vaccinated and unvaccinated patients who met these criteria were eligible to receive nirmatrelvir–ritonavir. After treatment, patients were contacted 8–10 days from the onset of symptoms to assess for treatment completion, adverse treatment effects, and symptom resolution.
After receiving approval by the University of Connecticut Health Center Institutional Review Board (IRB number 22x-213-1), we reviewed the medical records of pregnant patients who received nirmatrelvir–ritonavir, gathering baseline demographic information and assessing for adverse events from treatment. Patients were monitored throughout pregnancy and, if delivery occurred, through the immediate postpartum period to assess short-term pregnancy outcomes.
During the study time frame, 11 pregnant patients receiving care at the University of Connecticut Health Center were identified as candidates for nirmatrelvir–ritonavir treatment. All patients agreed to nirmatrelvir–ritonavir treatment (300 mg nirmatrelvir with 100 mg ritonavir orally twice daily for 5 days) after telehealth consultation with a maternal–fetal medicine specialist; however, four patients did not initiate treatment. The average time from symptom onset to treatment was approximately 2 days, and the average gestational age at the time of treatment was 26 3/7 weeks. Six patients were fully vaccinated, and four had received booster vaccinations (Table 1).
One patient developed dysgeusia, a well-documented side effect of nirmatrelvir–ritonavir,4 and stopped treatment after 2 days. The remaining six patients completed treatment without incident. All patients experienced symptom resolution without the need for additional care related to COVID-19.
One patient was induced at 37 2/7 weeks of gestation for cholestasis of pregnancy, and another spontaneously delivered a healthy neonate at 40 3/7 weeks of gestation. The latter patient was diagnosed with gestational hypertension shortly after admission. One patient opted for an elective induction of labor at 39 1/7 weeks of gestation and delivered a healthy neonate without complication. Four patients remain pregnant, with resolution of COVID-19 without additional pregnancy complications. No perinates experienced complications attributable to nirmatrelvir–ritonavir.
This case series describes short-term outcomes in seven pregnant patients with COVID-19 who received nirmatrelvir–ritonavir treatment and demonstrates that all patients who received nirmatrelvir–ritonavir experienced symptom resolution without the need for additional care. All but one patient tolerated nirmatrelvir–ritonavir treatment without immediate adverse effects, and no adverse fetal effects were observed. Despite these reassuring findings, more studies are needed to examine the efficacy and safety of oral antiviral treatments against different COVID-19 variants during pregnancy, in addition to long-term maternal and neonatal outcomes.
1. Centers for Disease Control and Prevention. Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. Accessed May 23, 2022. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19
2. Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022;386:1397–408. doi: 10.1056/NEJMoa2118542
3. Pfizer. Pfizer shares in vitro efficacy of novel COVID-19 oral treatment against Omicron variant. Accessed May 23, 2022. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-vitro-efficacy-novel-covid-19-oral-treatment
4. National Institutes of Health. COVID-19 treatment guidelines. Ritonavir-boosted nirmatrelvir (Paxlovid). Accessed May 20, 2022. https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/