Short-Term Pregnancy Outcomes Following Monoclonal Antibody Treatment for COVID-19 Infection during the Omicron Surge

Introduction

Pregnant patients who contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) are at increased risk for developing pneumonia, acute respiratory distress syndrome, ICU admission, invasive ventilation and death compared with nonpregnant patients [1, 2, 3]. To prevent progression to severe disease, the use of monoclonal antibodies has been recommended in non-hospitalized COVID-19 positive pregnant individuals with mild to moderate symptoms. However, these monoclonal antibodies have not been well studied in pregnancy, and there is insufficient evidence to determine overall safety and efficacy. Despite these concerns, monoclonal antibodies are being widely used in pregnancy, with recently reports suggesting that this therapy is well tolerated in pregnancy and prevents progression to severe disease [4, 5, 6]. Use of monoclonal antibodies has become further complicated by the recent emergence of the Omicron variant of SARS-CoV-2 as the dominant strain worldwide due to the potential for reduced effectiveness of monoclonal antibodies against this variant. One study showed a marked loss of inhibitory activity against the Omicron variant by several of the most highly neutralizing monoclonal antibodies currently in use [7].

Objective

The purpose of this case series was to assess short-term outcomes of mAb treatment in COVID-19 positive pregnant patients during the Omicron surge.

Study Design

This study was approved by the University of Connecticut Health Center IRB. Medical records of pregnant patients who received mAbs from December 1, 2021, through March 18, 2022 were reviewed. Patients were eligible to receive mAb treatment if they tested positive for SARS- CoV-2 based on nasopharyngeal polymerase chain reaction test, had symptoms within 7 days and did not meet criteria for admission. Patients received (1) sotrovimab, or (2) bamlanivimab/etesivimab, or (3) casirivimab/imdevimab in the emergency department or infusion center. Patients were monitored for 1-hour for adverse effects.

Results

Twenty-one pregnant patients received mAbs during the Omicron surge (Table 1). Of the 9 patients who were fully vaccinated, 4 had completed their booster. The average time from diagnosis to infusion was 3 days. The average gestational age at time of treatment was 26 weeks. Two patients received casirivimab/imdevimab and 5 patients received bamlanivimab/etesivimab, administered prior to the recommendation by the U.S. Food and Drug Administration that these mAb treatments should not be used when Omicron is suspected because of markedly reduced activity against this variant. The remainder of patients received sotrovimab.

The short-term maternal outcomes for most of our cohort were favorable. One patient developed an anaphylactic reaction following infusion of bamlanivimab/etesevimab. One patient required admission to the intermediate care unit for severe COVID-19 fifteen days following infusion, and a second patient developed cardiorespiratory symptoms concerning for post-acute sequelae SARS-CoV-2 infection.

Adverse pregnancy outcomes were present in 43.7% of our delivered cohort (n=16). One patient underwent cesarean delivery at 38w6d for worsening COVID- induced maternal hypoxia. One patient had spontaneous preterm birth of a healthy neonate at 35w2d and another patient was medically induced at 34w0d for superimposed preeclampsia with severe features. Four patients underwent a medical induction of labor at term for gestational hypertension (gHTN) (n=2), fetal growth restriction (FGR) in the setting of gHTN (n=1), and oligohydramnios (n=1). Of the four patients who remain pregnant with resolution of COVID-19, one is currently being followed for early-onset, severe FGR.

Conclusion

This case series describes short-term outcomes in 21 pregnant patients with SARS-CoV-2 who received mAb treatment during the Omicron surge, demonstrating that most patients who receive mAb treatment experience symptom resolution without the need for additional care. All but one patient tolerated mAb infusion without immediate adverse effects. Our study is limited by lack of a comparison group and hence, our conclusions run the risk of being non-representative. Further, we cannot draw definitive conclusions that our favorable patient outcomes were a direct result of mAB treatment and not due to other variables. Despite this limitation, our reassuring study findings are consistent with other studies evaluating patients receiving mAb treatment prior to the Omicron variant [8, 9]. further research evaluating a larger; more diverse population of patients is warranted. In addition, more studies are needed to examine the efficacy and safety of mAbs against different variants during pregnancy, and long-term maternal and neonatal outcomes.

Headache, myalgias, chest pain, nausea, vomiting

4 3 23+6

2 1 24+2 Headache, sore throat None 29.48 sotrovimab 2 None None Delivered 38+0 Vaginal 3260 None Placenta not sent Cough, sore throat, nausea, myalgias

4 3 27+5

1 0 30+1 Nausea, vomiting Obesity 37.1 sotrovimab 2 None

3 1 35+0 Shortness of breath None 26.6 sotrovimab 5 None None Delivered 40+0 Vaginal 3630 None Placenta not sent Cough, congestion, rhinorrhea, chills

2 1 26+1 Cough, congestion, shortness of breath

3 0 31+4

3 2 27+2 Congestion, myalgias Asthma 20.9 sotrovimab 2 None None Delivered 38+4 Vaginal 3430 None Placenta not sent

3 1 14+1 Congestion, headache, myalgias Obesity 31.6 sotrovimab 4 None None Pregnant

3 2 35+1 Congestion, nausea, myalgias Obesity 37.4 sotrovimab 2 None Gestational Hypertension Delivered 39+5 Vaginal 3690 None Placenta not sent

2 1 35+3 Cough Obesity 34.6 sotrovimab 7 None Gestational Hypertension Delivered 37+5 Vaginal 2720 None Placenta not sent

3 2 31+5 Fever, cough, congestion Obesity 30.9 sotrovimab 2 None Cholestasis of Pregnancy

Chronic Hypertension 28.3 bamlanivimabetesevimab 2 None Unexplained elevated msAFP (2.06 MoM) Delivered 39+0 Vaginal birth after cesarean 3660 None Placenta not sent Obesity 35.6 sotrovimab 4 None None Delivered 39+4 Vaginal 3310 None Placenta not sent Small placenta, chronic villitis Vacuum assisted vaginal delivery Fetal tachyarrhythmia (resolved during pregnancy)

3620 None

Delivered 40+1

Obesity 37.1 sotrovimab 2 None None Delivered 39+1 Cesarean 3827 None Placenta not sent None 28.72 sotrovimab 5 None None Delivered 39+2 Vaginal 3400 None Placenta not sent Delivered at outside hospital Un- known Unknown Un- known Unknown