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Review 1: "Impact of SARS-CoV-2 Variant on the Severity of Maternal Infection and Perinatal Outcomes: Data from the UK Obstetric Surveillance System National Cohort"

Published onJul 27, 2022
Review 1: "Impact of SARS-CoV-2 Variant on the Severity of Maternal Infection and Perinatal Outcomes: Data from the UK Obstetric Surveillance System National Cohort"
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key-enterThis Pub is a Review of
Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort

ABSTRACTBackgroundIn the UK, the Alpha variant of SARS-CoV-2 became dominant in late 2020, rapidly succeeded by the Delta variant in May 2021. The aim of this study was to compare the impact of these variants on severity of maternal infection and perinatal outcomes within the time-periods in which they predominated.MethodsThis national, prospective cohort study collated data on hospitalised pregnant women with symptoms of confirmed SARS-CoV-2 infection and compared the severity of infection and perinatal outcomes across the Wildtype (01/03/20-30/11/20), Alpha (01/12/20-15/05/21) and Delta dominant periods (16/05/21-11/07/21), using multivariable logistic regression.FindingsOf 3371 pregnant women, the proportion that experienced moderate to severe infection significantly increased between Wildtype and Alpha periods (24.4% vs. 35.8%; aOR1.75 95%CI 1.48-2.06), and between Alpha and Delta periods (35.8% vs. 45.0%; aOR1.53, 95%CI 1.07-2.17). Compared to the Wildtype period, symptomatic women admitted in the Alpha period were more likely to require respiratory support (27.2% vs. 20.3%, aOR1.39, 95%CI 1.13-1.78), have pneumonia (27.5% vs. 19.1%, aOR1.65, 95%CI 1.38-1.98) and be admitted to intensive care (11.3% vs. 7.7%, aOR1.61, 95%CI 1.24-2.10). Women admitted during the Delta period had further increased risk of pneumonia (36.8% vs. 27.5%, aOR1.64 95%CI 1.14-2.35). No fully vaccinated pregnant women were admitted between 01/02/2021 when vaccination data collection commenced and 11/07/2021. The proportion of women receiving pharmacological therapies for SARS-CoV-2 management was low, even in those critically ill.InterpretationSARS-CoV-2 infection during Alpha and Delta dominant periods was associated with more severe infection and worse pregnancy outcomes compared to the Wildtype infection, which itself increased risk compared to women without SARS-CoV-2 infection.1 Clinicians need to be aware and implement COVID-specific therapies in keeping with national guidance. Urgent action to tackle vaccine misinformation and policy change to prioritise uptake in pregnancy is essential.FundingNational Institute for Health Research HS&DR Programme (11/46/12).

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.



This is an observational study with information on 3,371 pregnant persons admitted to the hospital with symptomatic COVID-19 infection during three distinct time periods during the COVID-19 pandemic. The main conclusions suggest that pregnant persons admitted to the hospital with symptomatic COVID-19 during the Delta period have worse health outcomes than those during the Alpha period. (And, similarly, worse health outcomes were noted in the Alpha vs. Wildtype period.) A major strength of this study is that the study data arises from an excellent data source as it contains all pregnant persons admitted to the hospital (UK Obstetric Surveillance System). Although the analytic methods are justified, there are two potential gaps in the analysis that could impact the main claims:

1. Seasonality in outcomes: If there is a strong seasonal trend in any of the presented outcomes, this could explain some of the differences between the time periods. For example, if admission to the neonatal unit is more likely in the winter months, this could underestimate the toll of Delta as compared to Alpha or Wildtype. This could be investigated by looking at seasonal trends in health outcomes prior to COVID-19.

2. Selection bias: The analysis only contains information on pregnant persons after they are admitted to the hospital with symptomatic COVID-19. Selection bias may be present if the underlying population is changing over time. This is problematic as vaccinations in the UK increased during the Delta period, potentially causing pregnant persons who would have ended up in the “symptomatic and included” study group had they not been vaccinated to now be excluded because they were vaccinated and asymptomatic. It seems the authors could clarify this by providing more information on vaccination status in the symptomatic (included) and asymptomatic (excluded) groups.

Overall, it seems like the authors missed an opportunity to dive deeper into the vaccination statuses of the Delta and Alpha time periods. Further, it is unclear if the missingness in the Alpha period is because a portion of the time period predates widespread vaccine uptake (December 2020 - February 2021). If that is the case, a subanalysis with vaccinated individuals may be possible.

As a final cautionary note: reporting the proportion of admitted persons that were vaccinated, as was done in the paper, is problematic because it is highly dependent on the proportion vaccinated in the population. As vaccinations increase (Alpha to Delta period), a greater proportion of the admitted persons will be vaccinated – often leading to misleading headlines in the press.

Since our solicitation of reviews, this preprint has been published in BMJ journal and the link to the published manuscript can be found here.

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