Impact of SARS-CoV-2 variant on the severity of maternal infection and perinatal outcomes: Data from the UK Obstetric Surveillance System national cohort

  1. Nicola Vousden
  2. Rema Ramakrishnan
  3. Kathryn Bunch
  4. Edward Morris
  5. Nigel Simpson
  6. Christopher Gale
  7. Patrick O’Brien
  8. Maria Quigley
  9. Peter Brocklehurst
  10. Jennifer J Kurinczuk
  11. Marian Knight

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Abstract

Background

In 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.

Methods

This 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.

Findings

Of 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.

Interpretation

SARS-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.

Funding

National Institute for Health Research HS&DR Programme (11/46/12).

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  3. ScreenIT

    SciScore for 10.1101/2021.07.22.21261000: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variableNominated reporting clinicians, facilitated by research midwives and nurses from the UK’s National Institute of Health Research Clinical Research Network, notified all pregnant women admitted to their hospital with confirmed SARS-CoV-2 infection.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisIn this national observational study, the study sample size was governed by the disease incidence, thus no formal power calculation was carried out.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical methods and analysis: Statistical analyses were performed using STATA version 15 (Statacorp, TX, USA).
    STATA
    suggested: (Stata, RRID:SCR_012763)
    Statacorp
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Whilst it is a limitation that women with mild infection diagnosed and treated in the community will not be included in this study, it is highly likely that all women with severe infection would have been captured. A further limitation of our study is that variant sequencing data were not available for individual women, therefore proxy time periods were utilised instead. However, the Delta VOC is now known to have contributed more than 90% of all sequenced cases since 7th June 2021 so major contamination is unlikely.17 Other time-dependent changes will exist which we cannot account for, for example varying thresholds for admission to hospital or ICU depending on clinician familiarity with managing COVID-19. In the general population, national guidance was updated in January 2021 to inform community management of those with oxygen saturations >92%.18 However, it is unclear that this admission threshold was used extensively in pregnancy and given that the RCOG has never released national admission guidance for pregnant patients, this is unlikely to account for differences observed. Differing thresholds based on bed capacity may have been a contributory factor during the peak of the Alpha VOC when hospital pressures may have restricted admission to the most severe cases. However, this is not supported by our finding of an increased proportion of admissions primarily for COVID-19 in this time compared to the Wildtype period. In addition, current hospital pressures from COVID-19 (...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2021.07.22.21261000v1 on medRxiv