Severity of SARS-CoV-2 Infection in Pregnancy in Ontario: A Matched Cohort Analysis

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 SARS-CoV-2 pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than non-pregnant people to accept vaccination. We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy. Methods Our study made use of a population-based SARS-CoV-2 case file from Ontario, Canada. Due to both 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 to 49 years old). Risk of severe SARS-CoV-2 outcomes (hospitalization or intensive care unit (ICU) admission) was evaluated in pregnant women and time-matched non-pregnant controls using multivariable conditional logistic regression. Results Compared to the rest of the population, non-pregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio (SMR) 1.28), while risk of infection was reduced among pregnant women (SMR 0.43). After adjustment for age, comorbidity, healthcare worker status, vaccination, and infecting viral variant, pregnant women had a markedly elevated risk of hospitalization (adjusted OR 4.96, 95% CI 3.86 to 6.37) and ICU admission (adjusted OR 6.58, 95% CI 3.29 to 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 0.004). Interpretation A time-matched cohort study suggests that while pregnant women may be at a decreased risk of infection relative to the rest of the population, their risk of severe illness is markedly elevated if infection occurs. Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favours SARS-CoV-2 vaccination in pregnant women. ### Competing Interest Statement Declaration of competing interests: DNF has served on advisory boards related to influenza and SARS-CoV-2 vaccines for Seqirus, Pfizer, Astrazeneca and Sanofi-Pasteur Vaccines, and has served as a legal expert on issues related to COVID-19 epidemiology for the Elementary Teachers Federation of Ontario and the Registered Nurses Association of Ontario. ART was employed by the Public Health Agency of Canada when the research was conducted. The work does not represent the views of the Public Health Agency of Canada. ### Funding Statement The research was supported by a grant to DNF from the Canadians Institutes for Health Research (2019 COVID-19 rapid researching funding OV4-170360). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our study was conducted in accordance with the STROBE guidelines for observational research, and received ethics approval from the Research Ethics Board at the University of Toronto. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Our study was conducted in accordance with the STROBE guidelines for observational research, and received ethics approval from the Research Ethics Board at the University of Toronto.