Safety of Monoclonal Antibodies as Treatment for Coronavirus Disease 2019 (COVID-19) During Pregnancy

Abstract

OBJECTIVE: Pregnant patients are at increased risk of severe illness, in-hospital mortality, and preterm birth in the setting of coronavirus disease 2019 (COVID-19); however, they often are excluded from clinical trials that analyze improved therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thus, there are relatively few available data that examine the safety of monoclonal antibodies (mAbs) in pregnant patients with COVID-19, which we aimed to explore in this systematic review. DATA SOURCES: We searched PubMed, Cochrane, EMBASE, and Google Scholar on September 30, 2022. Included studies encompassed English-language case reports with at least five participants, cross-sectional studies, case–control studies, cohort studies, retrospective or prospective chart reviews, and randomized controlled trials that enrolled pregnant women who received SARS-CoV-2–targeted mAbs. Studies were screened for eligibility using Covidence according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines and were subsequently evaluated for risk of bias with the JBI critical appraisal checklist. TABULATION, INTEGRATION, AND RESULTS: Initial search yielded 616 studies; 13 publications were ultimately eligible. Pregnant patients were treated with SARS-CoV-2–neutralizing mAbs casirivimab-imdevimab, bamlanivimab, or bamlanivimab-etesevimab. A total of 365 patients were treated with casirivimab-imdevimab, 13 were treated with bamlanivimab, and 11 were treated with bamlanivimab-etesevimab. There were no cases of maternal mortality. Eighteen of the 389 patients had adverse effects related to mAb administration—all resolved. Of the patients treated with casirivimab-imdevimab, there were 35 preterm deliveries, two fetal deaths, one neonatal death due to sepsis, five cases of preterm prelabor rupture of membranes (PROM), one case of PROM, and 24 neonatal intensive care unit (NICU) admissions. Of the patients treated with bamlanivimab, there was one case of preterm PROM and one preterm delivery. There were no NICU admissions in the bamlanivimab or bamlanivimab-etesevimab cohorts. CONCLUSION: Preliminary data suggest that neutralizing mAb treatment for COVID-19 in pregnant patients is safe. However, treatment-associated events support the importance of clinical trials to determine the statistical significance of maternal and fetal outcomes in pregnant patients treated with SARS-CoV-2–targeted mAbs.