key: cord-0951798-l8le41s5
authors: Dashraath, Pradip; Nielsen-Saines, Karin; Madhi, Shabir A; Baud, David
title: COVID-19 vaccines and neglected pregnancy
date: 2020-08-27
journal: Lancet
DOI: 10.1016/s0140-6736(20)31822-5
sha: f485357fdddbbc022862d4512d19c78ded6f5b2a
doc_id: 951798
cord_uid: l8le41s5

nan

Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/ www.thelancet.com Vol 396 September 5, 2020 e22

On June 18, 2020, WHO presented a strategic framework to ensure the equitable allocation of scarce COVID-19 resources, including vaccines. 1 Health-care workers, people older than 65 years, and people with cardiovascular disease, chronic respiratory disease, cancer, diabetes, or obesity will be prioritised for initial vaccination. Pregnant women do not appear to constitute a high-priority group, despite representing a cohort who are at increased risk for severe complications of COVID-19. A growing body of evidence exists to suggest that pregnant women are at a higher risk of morbidity and mortality from COVID-19, including increased risk of respiratory failure with the need for admission to intensive care and mechanical ventilation, compared with age-matched women who are not pregnant. 2,3 COVID-19 has also been associated with an increased rate of stillbirth. 4 Two trials of adenovirus-vectored vaccines (phase 1/2 and phase 2) 5,6 for COVID-19 have shown sustained T-cell and neutralising antibody responses against the trimeric spike glycoprotein of severe acute respiratory syndrome coronavirus 2 in healthy adult participants who were not pregnant. Replication-defective adenoviruses, when chemically attenuated, are ideal vectors because of their ability to accommodate large transgenes and encode proteins without viral integration into the host cell genome.

ChAdOx1, the chimpanzee adenovirus-vectored vaccine platform that was used in the Oxford trials, 5 has previously been shown to safely induce potent humoral and cell-mediated immune responses that confer robust protection from Rift Valley fever disease in pregnant sheep that were vaccinated in the first trimester, without risks of maternal viraemia or miscarriage. 7 Murine studies of gorilla adenovirus-vectored vaccines for Zika virus have similarly been shown to prevent in-utero transmission of Zika virus. 8 The immunity paradox during pregnancy that favours tolerance to the fetus (ie, stops the maternal immune system from rejecting the fetus), but leaves the mother susceptible to viral infections, can be opportunistically leveraged by simian adenoviral vectors. The ChAdOx1 vaccine platform is non-replicating and could be used to deliver proteins to the mother for the induction of an immune response without adversely affecting the fetus. Transplacental transfer of maternal induced antibodies can ensue, but without transfer of the virus vector to the fetus. Unfortunately, pregnant women have historically been excluded from pharmaceutical research, owing to well intentioned, but sometimes misguided, concerns about fetal safety.

The development of an effective COVID-19 vaccine is a global health priority. Pregnant women, who are at increased risk of adverse outcomes from COVID-19, would be additionally harmed if they were unable to access evidence-based chemoprophylaxis from vaccine trials. WHO's global commitment to fair access to COVID-19 vaccines should, therefore, include pregnant women. Accordingly, we advocate that pregnant women should be included in the phase 3 trial protocols of adenovirus-vectored vaccines and also protein-based vaccines (eg, NVX-CoV2373, a recombinant nanoparticle vaccine [NCT04368988]) for COVID-19, for which there are even less safety concerns, and implore international obstetric societies to endorse their recruitment. The protocols should include provisions for monitoring of maternal and fetal safety and for documentation of iatrogenic complications, including follow-up of offspring after delivery. 

A global framework to ensure equitable and fair allocation of COVID-19 products. WHO Member States briefing

Characteristics of women of reproductive age with laboratoryconfirmed SARS-CoV-2 infection by pregnancy status-United States

Public Health Agency of Sweden's brief report: pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in intensive care in Sweden

Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebocontrolled, phase 2 trial

Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats

A gorilla adenovirus-based vaccine against Zika virus induces durable immunity and confers protection in pregnancy