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More severe infection associated with variants in pregnant women

2nd August 2021

Infection with the Alpha and Delta COVID-19 variants was associated with severe infection and worse outcomes for pregnant women.

Women pregnant infected with COVID are more likely to be admitted to an intensive care unit (ICU) or need invasive ventilation. During the pandemic, two separate variants have emerged; alpha and delta, with the former becoming the dominant variant until May 2021, when it was superseded by the latter. While there is evidence that both the alpha and the delta are associated with a greater level of transmissibility and hospitalisations in the non-pregnant population, there is limited published comparative information of the impact of the original (wild-type) and the alpha and delta variants in pregnant women. The evidence that is available, would suggest that the delta variant lead to more admissions to an ICU.

In the absence of such comparative data, a team from the National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Oxford, UK, sought to examine the differences of these different variants on the severity of maternal infection over time. The study was part of the Obstetric Surveillance System which is a research platform that records information on specific pregnancy complications. The primary outcome measure was a composite indicating moderate to severe COVID-19 infection: oxygen saturation < 95% on admission, the need for oxygen therapy, evidence of pneumonia on imaging, admission to an ICU or maternal death. Although the individual patient-level data did not indicate the specific variant responsible for infection, the outcomes were collected for hospitalised pregnant women with confirmed COVID-19 infection or within two days of giving birth, across the periods of time in which the wild-type (original strain), the alpha and delta variant were dominant.

Findings
There were 3371 women admitted to hospital across the three time periods and the majority of admissions occurred during the period for which the alpha variant was dominant. From 2521 admissions during this period, just under half (45%) were due to COVID-19. Overall, the proportion of COVID-19 related admissions increased across the variants from 41.1% (wild-type), 45.9% (Alpha) and 54.2% (Delta). The proportion of women hospitalised with at least one marker of moderate to severe disease increased from 25% (wild-type) to 35.8% (Alpha) and 45% (Selta). Women admitted during the alpha period were significantly more likely to require admission to ICU than during the wild-type period (odd ratio, OR = 1.61, 95% CI 1.24–2.10) and while there was a slightly higher rate of admission during the Delta vs Alpha period, this difference was not significant. Fortunately, the majority of babies were live born with no differences in the proportion of stillbirths across the different time periods.

In their discussion, the authors commented on how the delta variant caused the biggest increase in symptomatic pregnant women and appeared to experience more severe disease though the difference was not statistically significant. They concluded that pregnant women appear to be at an increased risk of more severe infection and admission to ICU and should be considered as a priority group for vaccination.

Citation
Vousden N et al. Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort. MedRxiv 2021

Immunogenicity occurs in pregnant and lactating women after COVID-19 vaccination

17th May 2021

Real-world data indicate that both pregnant and breast-feeding women are able to generate a satisfactory immune response after vaccination against COVID-19.

With pregnant women excluded from the COVID-19 vaccination trials, it remained uncertain whether those who were either pregnant or breast-feeding would develop satisfactory immunogenicity, especially given the evidence of more severe outcomes after infection in those who are pregnant. While there are some data to indicate that vaccination against other viruses such as influenza confers immunity, much less is known about COVID-19 vaccination and the efficacy in lactating mothers. In addition, with the emergence of an increasing number of COVID-19 variants, there is an urgent need to examine whether a sufficient antibody titre against COVID-19 and new variants is generated within these two patient cohorts. Consequently, a team from the Department of Obstetrics and Gynaecology, Boston, US, set out to answer this question prospectively following up on a number of women who received a COVID-19 vaccination between December 2020 and March 2021. The team also included a group of pregnant/non-pregnant women/unvaccinated women who had been previously infected with COVID-19 and who provided serum samples for comparative purposes.

Findings
A total of 103 participants were enrolled in the study comprising 57 who were non-pregnant, 30 pregnant and 16 lactating women. The median age of the pregnant and lactating women was 35 years and the majority (over 80%) were of white ethnicity. Most (63%) pregnant women had received the mRNA-1272 (Moderna) vaccine whereas the majority of lactating mothers (69%) had the BNT162b vaccine. Serum samples were taken a median of 21 days after the second vaccination dose for non/pregnant individuals and 26 days for lactating mothers. In addition, nine women gave birth and contributed infant cord blood. The level of receptor-binding domain (RBD) antibody titres in non-pregnant, pregnant and lactating were similar but higher than among those who had a prior COVID-19 infection, irrespective of pregnancy status. In cord samples, the levels of RBD antibodies were similar in mothers compared to cord samples (14,953 vs 19,873) among those who had been vaccinated but lower in non-vaccinated, but previously infected women (1342 vs 635). Interestingly, there were higher median levels of antibodies in breast milk among those who had a prior infection compared to vaccinated women (203 vs 97). Although RBD antibodies to the wild-type COVID-19 were comparable across the different groups, there was a 3.5-fold lower titre against the B.1.1.7 (UK variant) and a 6-fold lower titre for the B.1.351 (South African variant). Despite these lower titre levels, responses to non-neutralising antibodies and T-cell responses were preserved in both pregnant and non-pregnant women to the variants of concern, suggesting that cellular immune responses may be important for protection.

Commenting on these results, the authors noted how their data confirm other findings of a higher vaccine-induced antibody response compared to prior infection.

They concluded that while the results are based on a small sample size, the presence of neutralising antibodies in both cord and breast milk samples reveals how newborns are protected by maternal vaccination.

Citation
Collier AY et al. Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. JAMA 2021