Efficacy and safety of monoclonal antibodies against SARS-CoV-2 during pregnancy

By Dr. Sanchari Sinha Dutta, Ph.D.Reviewed by Emily Henderson, B.Sc.Sep 13 2022

In an article published in the journal Expert Opinion on Drug Safety, scientists have described the safety and efficacy profiles of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibodies in pregnant women with coronavirus disease 2019 (COVID-19).

Editorial: Safety and efficacy of monoclonal antibodies anti SARS-CoV-2 in pregnancy. Image Credit: Naeblys / Shutterstock

Background

Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been considered a potential therapeutic approach to managing COVID-19 outcomes. These antibodies work by binding various spike epitopes and subsequently preventing the viral spike–host angiotensin-converting enzyme 2 (ACE2) interaction. ACE2 is the host cell receptor that allows SARS-CoV-2 to enter cells via viral envelop – host cell membrane fusion.

Clinical trials have indicated that monoclonal antibodies can reduce the risk of severe COVID-19 by more than 70%. Therefore, the treatment with casirivimab, imdevimab, and sotrovimab have been indicated for high-risk COVID-19 patients who do not require oxygen supplementation. A combination of casirivimab and imdevimab has also been used as post-exposure prophylaxis among close contacts of symptomatic patients.

Therapeutic management of pregnant women with COVID-19

In pregnant women, COVID-19 has been found to increase the risk of admission to the intensive care unit (ICU) and mortality. The disease is also known to cause neonatal complications.

Dexamethasone, a corticosteroid, has been used widely in treating COVID-19 patients. In clinical trials, this drug has significantly reduced the 28-day mortality in COVID-19 patients.

Since dexamethasone is known to cross the placenta and affect fetal development, it is not recommended for treating pregnant women with COVID-19. According to the Royal College of Obstetricians and Gynecologists, pregnant women with severe COVID-19 should be treated with prednisolone or hydrocortisone instead of dexamethasone. However, no clear evidence is available regarding the therapeutic efficacy of these steroids during pregnancy.

Among available repurposed antiviral drugs, remdesivir is recommended for pregnant women with progressive COVID-19. Overall, this drug is safe and well-tolerated among pregnant women with COVID-19.

A combination of Nirmatrelvir and ritonavir has been recommended for pregnant women with comorbidities that may put them at higher risk for developing severe COVID-19. These drugs are also well-tolerated by pregnant women. However, because of the possibility of fetal toxicity, molnupiravir is not recommended for use during pregnancy.     

Monoclonal antibody treatment during pregnancy

Evidence collected from clinical trials and real-world setups has confirmed the safety and efficacy of anti-SARS-CoV-2 monoclonal antibodies in pregnant women who do not require oxygen supplementation. The combinations of casirivimab, imdevimab, bamlanivimab, and etesevimab have particularly been promising.

In overweight/obese pregnant women (gestational age: 11 – 32 weeks), treatment with monoclonal antibodies has been found to prevent COVID-19 progression and hospitalization.

In unvaccinated pregnant women with moderate COVID-19, no treatment-related adversities or symptom worsening have been observed following the administration of casirivimab and imdevimab.

In a large-scale study involving 51 pregnant women with mild-to-moderate COVID-19, no immediate adverse effects have been observed following treatment with casirivimab and imdevimab or bamlanivimab and etesevimab. Among the study participants, 21% were obese, and 1.9% required hospitalization.

Another study involving 30 pregnant women with COVID-19 has described that treatment with monoclonal antibodies helps improve symptoms in 85% of the participants. Treatment-related adversities, including hypotension and dizziness, have been observed in only one participant.

In another study, treatment with casirivimab and imdevimab or bamlanivimab and etesevimab has been found to induce transient systemic reaction (alteration in fetal heart rate) in 2 out of 15 pregnant women with mild-to-moderate COVID-19. Only one woman delivered after antibody infusion because of maternal and fetal clinical deterioration.

One recent study involving hospitalized pregnant women requiring oxygen therapy has shown that treatment with casirivimab and imdevimab helps resolve COVID-19-related symptoms and prevent clinical deterioration. No treatment-related adversities have been observed among the participants.

The combination treatment with casirivimab and imdevimab has been approved for treating pregnant women with COVID-19 who are seronegative for anti-SARS-CoV-2 spike antibodies at baseline.

Overall, these observations highlight the safety and efficacy of monoclonal antibodies during pregnancy. The primary treatment benefits include improving symptoms and preventing progression to severe COVID-19, hospitalization, and death.