Nirmatrelvir/ritonavir use in pregnant women with SARS-CoV-2 Omicron infection: a target trial emulation.

To date there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in SARS-CoV-2-infected pregnant persons. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized pregnant women with symptomatic SARS-CoV-2 Omicron variant infection. Among patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within five days of symptom onset or COVID-19 diagnosis. Primary outcomes were maternal morbidity and mortality index (MMMI), all-cause maternal death, and COVID-19-related hospitalization, while secondary outcomes were individual components of MMMI, preterm birth, stillbirth, neonatal death, and caesarean section. One-to-ten propensity-score matching was conducted between nirmatrelvir/ritonavir users and non-users; followed by cloning, censoring, and weighting. Overall, 211 pregnant women on nirmatrelvir/ritonavir and 1,998 non-users were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28-day MMMI risk (absolute risk reduction [ARR] = 1.47%, 95%CI = 0.21%-2.34%); but not 28-day COVID-19-related hospitalization (ARR = -0.09%, 95%CI = -1.08%-0.71%). Nirmatrelvir/ritonavir treatment was also associated with reduced risks of caesarean section (ARR = 1.58%, 95%CI = 0.85%-2.39%); and preterm birth (ARR = 2.70%, 95%CI = 0.98%-5.31%). No events of maternal or neonatal death or stillbirth were recorded. The findings suggest nirmatrelvir/ritonavir is an effective treatment in symptomatic pregnant women with SARS-CoV-2 Omicron variant infection.