Pregnancy outcomes after administration of monoclonal antibody therapy for COVID-19.

OBJECTIVE: SARS-CoV-2 was initially identified in Wuhan, China, and was discovered to be the causative agent of COVID-19. Since then, it has spread throughout the world and was declared a pandemic in March 2020. Novel treatments have been used in an attempt to reduce the severity, morbidity, and mortality of the disease. It has been shown that pregnant patients are at significantly higher risk of requiring hospital admission, mortality, and presenting perinatal complications because of COVID-19.1Zambrano LD Ellington S Strid P et al.Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1641-1647Crossref PubMed Google Scholar,2Lokken EM Huebner EM Taylor GG et al.Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.Am J Obstet Gynecol. 2021; 225 (77.e1–14)Google Scholar An update from the Centers for Disease Control and Prevention found that pregnant patients were 4 times more likely to require invasive ventilation than nonpregnant patients of the same age. In addition, they uncovered significant health disparities. Pregnant Asian and Native Hawaiian or Pacific Islander women had higher intensive care unit admissions. Hispanics and African Americans also had disproportionate rates of SARS-CoV-2 infection and a higher risk of hospitalization.1Zambrano LD Ellington S Strid P et al.Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1641-1647Crossref PubMed Google Scholar,3Delahoy MJ Whitaker M O'Halloran A et al.Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 - COVID-NET, 13 states, March 1-August 22, 2020.MMWR Morb Mortal Wkly Rep. 2020; 69: 1347-1354Crossref PubMed Google Scholar Based on results from randomized controlled trials, several antispike monoclonal antibodies (mAbs) received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) in 2021.4Gottlieb RL Nirula A Chen P et al.Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial.JAMA. 2021; 325: 632-644Crossref PubMed Scopus (619) Google Scholar, 5Weinreich DM Sivapalasingam S Norton T et al.REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19.N Engl J Med. 2021; 384: 238-251Crossref PubMed Scopus (1065) Google Scholar, 6Gupta A Gonzalez-Rojas Y Juarez E et al.Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab.N Engl J Med. 2021; 385: 1941-1950Crossref PubMed Scopus (550) Google Scholar However, pregnant patients were not included in the clinical trials, and the effects on pregnancy outcomes are unknown. In this case series, we described the outcomes of 47 pregnant patients who had confirmed COVID-19 and who received antispike mAb therapy. To the best of our knowledge, our study is the second largest report of this kind and includes the use of sotrovimab in 10 pregnant patients. STUDY DESIGN: After institutional review board approval, we performed a retrospective cohort study of 47 pregnant patients aged ≥18 years who received mAb infusion for the treatment of mild-to-moderate COVID-19 between April 2021 to January 2022. We extracted the data from St. Luke's University Health Network electronic medical record system. Mild disease was characterized by fever, change of taste or smell, and cough. Moderate disease was characterized by dyspnea, evidence of disease on imaging, or oxygen saturation of ≥94%. Severe disease was characterized by viral symptoms (mentioned in the definitions of mild and moderate diseases) with additional shortness of breath, and very severe disease was characterized by respiratory failure or shock. All patients had a confirmed positive result of direct SARS-CoV-2 testing. Patients were selected for mAb therapy if they met the eligibility criteria based on EUA guidelines released by the FDA and additional criteria defined by our institutional protocol (Figure). Pregnant patients were monitored for adverse reactions at the injection site, headache, dizziness, fever, weakness, nausea, vomiting, pruritus, rashes, anaphylaxis, diarrhea, and low blood pressure. We defined tolerability as a low rate of side effects and low admission rates. Data analysis was completed using SPSS (version 28; International Business Machines Corporation, Armonk, NY). RESULTS: A total of 47 pregnant patients were included in the study. The characteristics of the patient population are displayed in Table 1. The patients’ mean age was 30 years with most patients being White (85.1%). Most patients were obese (63.8%) and in their third trimester of pregnancy (57.4%). Most patients (46.8%) received bamlanivimab and etesevimab treatment, and 10 patients (21.3%) received sotrovimab.Table 1Characteristics of study patient populationMartinez-Baladejo. Monoclonal antibody therapy for COVID-19. Am J Obstet Gynecol MFM 2022.VariableNumeric valueAge range (y), mean±SD18–45: 30.19±5.269Race, n (%) White Black or African American American Indian or Alaska Native Other race40 (85.1)4 (8.5)1 (2.1)2 (4.3)Ethnicity, n (%) Not Hispanic or Latino or Spanish Hispanic or Latino Not reported or declined to answer39 (83.0)7 (14.9)1 (2.1)Language, n (%) English47 (100.0)Marital status, frequency (%) Single Married or civil union23 (48.9)24 (51.1)Comorbidities, n (%) BMI≥30 Hypertension Anxiety Depression Asthma Migraine Anemia during pregnancy Diabetes mellitus Vitamin D deficiency30 (63.8)9 (19.1)14 (29.8)15 (31.9)10 (21.3)11 (23.4)8 (17.0)8 (17.0)4 (8.5)Smoking history, n (%) Smoker Former smoker Nonsmoker4 (8.5)13 (27.7)30 (63.8)Obstetrical history, median (IQR) Gravida Para Abortions3 (1–8)1 (0–5)0 (0–4)Gestational age at infusion, n (%)First trimesterSecond trimesterThird trimester1 (1.1)19 (40.4)27 (57.4)Singleton pregnancies, n (%)46 (96.0)Twin pregnancies, n (%)2 (4.0)Delivered, n (%)46 (97.8): one patient lost to follow-upType of delivery, n (%) Cesarean delivery Spontaneous vaginal delivery Vacuum assisted vaginal delivery18 (39.0)26 (57.0)2 (4.0)BMI, body mass index; IQR, interquartile range; SD, standard deviation. Open table in a new tab BMI, body mass index; IQR, interquartile range; SD, standard deviation. Of note, 76% of the study population was unvaccinated. Moreover, 3 patients visited the emergency department (ED) after the infusion. Of the 3 patients, 2 had continuous COVID-19 symptoms, for which 1 patient was hospitalized because of COVID-19 pneumonia. The patient was unvaccinated and had obesity as a risk factor. Moreover, 1 patient presented to the ED because of decreased fetal movement, but this resolved during the admission as there was good feal movement on ultrasound and reassuring fetal heart tones. The nonstress test was reactive, and the amniotic fluid index was 8.28 cm. Of note, 1 pregnant patient received the infusion during early labor. The patient developed a fever during labor, but it was unclear whether this was related to the mAb infusion. Another patient received treatment after delivery without any adverse reactions or complications. There was no report of adverse effects 1 hour after the infusion or in follow-up (see other maternal clinical care outcomes in Table 3).Table 3Other maternal clinical care outcomesMartinez-Baladejo. Monoclonal antibody therapy for COVID-19. Am J Obstet Gynecol MFM 2022.Criterian (%)ED visits within 1 mo of infusionED visits related to infusion7 (15.2)0 (0)ED visits in the postpartum periodED visits related to infusion9 (19.6)0 (0)Patients undergoing DVT workup or diagnosed with DVT4 (8.7): one-fourth of patients positive for DVTRespiratory distress requiring imaging4 (8.7)DVT, deep vein thrombosis; ED, emergency department. Open table in a new tab DVT, deep vein thrombosis; ED, emergency department. As of January 2022, no miscarriage or intrauterine demise has been reported (more pregnancy outcomes in Table 2). Of note, 46 patients have thus far delivered, with 2 patients (4.3%) requiring a vacuum-assisted delivery and 18 patients (39.1%) requiring cesarean delivery. Moreover, 1 patient was lost to follow-up. Lastly, 3 neonates developed infections in the first 2 months of life (yeast dermatitis, neonatal conjunctivitis, and fever), but none of the infections were deemed attributable to the treatment.Table 2Pregnancy outcomesMartinez-Baladejo. Monoclonal antibody therapy for COVID-19. Am J Obstet Gynecol MFM 2022.Outcomesn (%)Miscarriage0 (0)Retained placenta1 (2.1)Preeclampsia6 (13.0)Hemorrhage requiring transfusion0 (0)NICU admission1 (2.2)Birthweight<2500 g5 (10.4)aThese data include 2 sets of twins and a neonate born at 38 weeks of gestation with low birthweight but had no other complication.Gestational age at delivery (wk)≤36.64 (8.7)37.0–40.041 (89.1)>40.61 (2.2)NICU, neonatal intensive care unit.a These data include 2 sets of twins and a neonate born at 38 weeks of gestation with low birthweight but had no other complication. Open table in a new tab NICU, neonatal intensive care unit. CONCLUSION: We described the use of antispike mAbs to treat mild to moderate COVID-19 in 47 pregnant patients. We found no conclusive evidence of maternal or fetal complications because of the treatment. Only 2 patients had progression of the disease, and only 1 patient required hospitalization. We would like to thank Meredith Birsner (Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, St. Luke's University Health Network, Bethlehem, PA) for the development of the project, Mathew Zangari and Christina Tran (Department of Graduate Medical Education, St. Luke's University Health Network, Bethlehem, PA) for assisting us with data extraction, and Jill Stoltzfus (Information Technology, St. Luke's University Health Network, Bethlehem, PA) for the data analysis.