Severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Pregnancy in Ontario: A Matched Cohort Analysis

  1. Kiera R Murison
  2. Alicia A Grima
  3. Alison E Simmons
  4. Ashleigh R Tuite
  5. David N Fisman

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Abstract

Background

Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination.

Methods

We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10–49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression.

Results

Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86–6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29–13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity, .004).

Conclusions

Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women.

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  1. Version published to 10.1093/cid/ciac544
  2. ScreenIT

    SciScore for 10.1101/2022.03.04.22271915: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Our study was conducted in accordance with the STROBE guidelines for observational research (28), and received ethics approval from the Research Ethics Board at the University of Toronto.
    IRB: Our study was conducted in accordance with the STROBE guidelines for observational research (28), and received ethics approval from the Research Ethics Board at the University of Toronto.
    Sex as a biological variableData Sources: As the likelihood of vaccination, the dominant SARS-CoV-2 variant, and the provincial public health response changed over time, we created a time-matched cohort of women infected with SARS-CoV-2 in pregnancy; non-pregnant controls were individuals with SARS-CoV-2 matched to pregnant women by date of positive laboratory test for SARS-CoV-2.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Like any observational study, ours is subject to several limitations. First, the inability to perform linkage of mothers and infants using available data prevents us from evaluating the question of whether maternal vaccination is likely to reduce risk associated with SARS-CoV-2 infection in live-born infants, though anti-spike antibody is present in infants born to vaccinated mothers, and is present at higher titres, and persists longer, than antibody in infants born to mothers with SARS-CoV-2 infection (31). The recent emergence of the Omicron variant makes us unable to explore the relative virulence of this variant in pregnancy in the current paper (23). Our estimates may also be subject to residual confounding by incompletely ascertained factors, including presence of underlying medical conditions. However, the very large effect size associated with pregnancy means that the magnitude of effect of putative confounding factors needed to explain away these associations would be implausibly large (32). In summary, we identify a large increase in risk of hospitalization and ICU admission in pregnant women infected with SARS-CoV-2 virus, relative to female controls of child-bearing age. This effect was not explained by comorbidity or vaccination status, and indeed, the relative increase in risk with pregnancy was greater when we restricted our analyses to women without medical comorbidities. Vaccination markedly reduced hospitalization and ICU admission risk in all women, pregna...

    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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  3. Version published to 10.1101/2022.03.04.22271915 on medRxiv