Persistent Elevated Risk of Severe COVID-19 Outcomes in Pregnant and Postpartum Individuals Beyond the Pandemic Emergency

Highlight

• Pregnant and postpartum individuals experience significantly higher risks of severe COVID-19-related hospitalizations compared to nonpregnant women even after the pandemic emergency period.
• During the Delta variant surge, pregnant individuals showed markedly elevated relative risks for COVID-19 hospitalization, pneumonia hospitalization, and severe composite outcomes.
• Although absolute risks declined postpandemic emergency, the relative risk of COVID-19 hospitalization during pregnancy remains more than four-fold greater than in nonpregnant women.
• Postpartum individuals also continue to demonstrate increased risk for severe COVID-19 outcomes, underscoring the vulnerability across the peripartum period.

Study Background

The COVID-19 pandemic has posed heightened risk challenges for pregnant and postpartum individuals, who are known to be vulnerable to respiratory infections with potentially severe complications. Early pandemic data highlighted increased rates of severe illness and adverse outcomes in pregnancy, including hospitalization, intensive care, and respiratory failure. However, with evolving viral variants, uptake of vaccination, and changes in public health measures, the risk profiles have shifted over time. Understanding the ongoing risks in pregnant and postpartum populations in the postpandemic emergency period is crucial for guiding obstetric management, vaccination recommendations, and health policy. This study specifically examines severe COVID-19 outcomes during the Delta variant predominance and the subsequent postemergency period in the United States, providing contemporary risk estimates in unvaccinated women of reproductive age.

Study Design

This was a retrospective cohort study conducted using a national U.S. commercial insurance claims database. The study population included women aged 18 to 49 years identified during two distinct periods: the Delta variant wave from July 1 to December 20, 2021, and the postpandemic emergency period from May 11, 2023 to September 10, 2024. Pregnant and postpartum women who were unvaccinated for COVID-19 during the year before follow-up were propensity score-matched to four nonpregnant women controls to balance baseline characteristics.

Primary outcomes analyzed were laboratory-confirmed or clinically diagnosed COVID-19 with subsequent hospitalization due to COVID-19, pneumonia hospitalization, or a severe composite COVID-19 hospitalization encompassing acute respiratory failure, intensive care unit admission, acute respiratory distress syndrome, or respiratory support. The matching approach and subsequent sensitivity analyses aimed to ensure robustness and reduce confounding.

Key Findings

From a total of 1,109,384 individuals during the Delta variant period and 878,003 during the postemergency period, hospitalization rates related to COVID-19 were substantially greater among pregnant individuals compared to postpartum and nonpregnant women.

In the Delta variant period, pregnancy was associated with significantly elevated risks for all primary outcomes:

• COVID-19 hospitalization risk increased markedly compared to matched nonpregnant women.
• Pneumonia hospitalization and severe composite hospitalizations were also notably higher.

During the postemergency period, while absolute risks decreased, the relative risks remained elevated:

• COVID-19 hospitalization had a relative risk (RR) of 4.09 (95% CI, 3.65-4.59) during pregnancy.
• Pneumonia hospitalization risk was significantly increased with an RR of 2.78 (95% CI, 1.38-4.81).
• The RR for severe composite COVID-19 hospitalization was 2.17 but with wide confidence intervals (95% CI, 0.35-6.67) indicating uncertainty due to fewer events.
• Postpartum individuals also exhibited elevated risks for severe COVID-19-related outcomes.

Sensitivity analyses reinforced the consistency of these findings across analytic methods.

Expert Commentary

These data confirm that pregnant and postpartum individuals remain at elevated risk for severe COVID-19 even beyond the acute phases of the pandemic. The persistently increased relative risks underscore that pregnancy constitutes a physiologic state conferring vulnerability to respiratory infections and complications including severe COVID-19. There is biological plausibility given pregnancy-associated immunologic and cardiopulmonary adaptations that may exacerbate respiratory illnesses.

The observed reduction in absolute risks during the postemergency period likely reflects accumulated population immunity and improved clinical management. Nevertheless, the relative risk elevation signals that tailored preventive strategies, including vaccination and early therapeutic interventions, remain critical in this population.

Limitations include reliance on claims data, which may have coding inaccuracies and lack granular clinical details such as viral sequencing or nuanced clinical parameters. The unvaccinated cohort focus provides insights into baseline risk absent vaccine protection but does not reflect vaccinated population outcomes. Furthermore, wide confidence intervals for severe composite outcomes postemergency highlight the need for larger studies or meta-analyses.

Conclusion

This large retrospective cohort study demonstrates that pregnancy and the postpartum period continue to carry higher risks for severe COVID-19 outcomes, including hospitalization and pneumonia, well after the official end of the pandemic emergency in the United States. Continued vigilance in clinical care, public health messaging, and vaccination efforts targeting pregnant and postpartum individuals is essential to mitigate these risks. Future research should focus on vaccinated cohorts, variant-specific risks, and long-term maternal and neonatal outcomes to inform comprehensive risk stratification and management guidelines.

Funding and ClinicalTrials.gov

The study utilized a commercial insurance claims database and did not report external funding sources or clinical trial registration.

References

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4. Zambrano LD, Ellington S, Strid P, et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641–1647.

5. CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. Risk for COVID-19 infection, hospitalization, and death by pregnancy status, age, race, and ethnicity among reproductive-aged women. Public Health Reports. 2023;138(3):305-314.