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Estimation of COVID-19 mRNA Vaccine Effectiveness Against Medically Attended COVID-19 in Pregnancy During Periods of Delta and Omicron Variant Predominance in the United States

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the estimated vaccine effectiveness (VE) of mRNA COVID-19 vaccines against medically attended COVID-19 during pregnancy?

Findings  In a case-control study including 5492 health care encounters sought by pregnant people, the estimated 2-dose VE against COVID-19–associated emergency department and urgent care encounters during Omicron predominance was not significantly different from 0; estimated 3-dose VE (last dose 7-119 days prior) was 79%. Against COVID-19–associated hospitalizations, 2-dose VE (14-149 days prior) was 86%, and 3-dose VE (7-119 days prior) was 86%; 2- and 3-dose VE estimates were not statistically different from 0 for doses 150 and more and 120 and more days prior.

Meaning  In this study, maternal vaccination, including booster dose, was associated with protection against serious COVID-19 during pregnancy.

Abstract

Importance  Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed.

Objective  To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance.

Design, Setting, and Participants  This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19–like illness (CLI) who underwent SARS-CoV-2 molecular testing.

Exposures  Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated.

Main Outcomes and Measures  Estimated VE against laboratory-confirmed COVID-19–associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 − aOR) × 100%.

Results  Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19–associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19–associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, −49% to 37%), 42% (95% CI, −16% to 72%), 79% (95% CI, 59% to 89%), and −124% (95% CI, −414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, −102% to 93%), 86% (95% CI, 28% to 97%), and −53% (95% CI, −1254% to 83%), respectively.

Conclusions and Relevance  In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19–associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.

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Article Information

Accepted for Publication: August 8, 2022.

Published: September 26, 2022. doi:10.1001/jamanetworkopen.2022.33273

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Schrag SJ et al. JAMA Network Open.

Corresponding Author: Ruth Link-Gelles, PhD, CDC COVID-19 Emergency Response Team, US Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30029 (hzt7@cdc.gov).

Author Contributions: Mx Butterfield and Dr Lazariu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Schrag and Verani contributed equally.

Concept and design: Schrag, Verani, Dixon, Butterfield, Vazquez-Benitez, Zerbo, Beaver, Ellington, Irving, Grannis, Midturi, Fadel, Link-Gelles, Valvi, Ball, Thompson, Naleway.

Acquisition, analysis, or interpretation of data: Schrag, Verani, Dixon, Page, Butterfield, Gaglani, Vazquez-Benitez, Zerbo, Natarajan, Ong, Lazariu, Rao, Ellington, Klein, Irving, Grannis, Kiduko, Barron, Dickerson, Lewis, Stockwell, Stenehjem, Link-Gelles, Murthy, Goddard, Grisel, Fireman, Arndorfer, Konatham, Thompson, Naleway.

Drafting of the manuscript: Schrag, Verani, Natarajan, Lazariu, Beaver, Grisel, Arndorfer.

Critical revision of the manuscript for important intellectual content: Schrag, Dixon, Page, Butterfield, Gaglani, Vazquez-Benitez, Zerbo, Ong, Lazariu, Rao, Beaver, Ellington, Klein, Irving, Grannis, Kiduko, Barron, Midturi, Dickerson, Lewis, Stockwell, Stenehjem, Fadel, Link-Gelles, Murthy, Goddard, Valvi, Fireman, Konatham, Ball, Thompson, Naleway.

Statistical analysis: Butterfield, Vazquez-Benitez, Zerbo, Lazariu, Fadel, Fireman.

Obtained funding: Klein, Irving, Goddard, Ball, Thompson.

Administrative, technical, or material support: Schrag, Verani, Dixon, Page, Butterfield, Gaglani, Natarajan, Ong, Lazariu, Ellington, Irving, Grannis, Kiduko, Dickerson, Lewis, Stenehjem, Goddard, Valvi, Arndorfer, Ball, Thompson.

Supervision: Schrag, Dixon, Ong, Klein, Grannis, Midturi, Thompson.

Conflict of Interest Disclosures: Dr Dixon reported receiving personal fees from Elsevier and Springer Nature and grants from the US Centers for Disease Control and Prevention (CDC) outside the submitted work. Dr Gaglani reported receiving grants from CDC–Abt Associates Baylor Scott & White Health during the conduct of the study and grants from CDC Baylor Scott & White Health, CDC–Abt Associates Baylor Scott & White Health, CDC–Vanderbilt University Medical Center, CDC–Westat Baylor Scott & White Health, and Janssen Baylor Scott & White Health outside the submitted work. Dr Vazquez-Benitez reported having a contract with the CDC during the conduct of the study and receiving grants from Sanofi outside the submitted work. Dr Natarajan reported receiving grants from the CDC during the conduct of the study. Dr Rao reported receiving grants from the CDC during the conduct of the study and grants from Biofire outside the submitted work. Dr Klein reported receiving grants from the CDC during the conduct of the study and grants from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur) outside the submitted work. Dr Irving reported receiving grants from the CDC to her institution, through a contract mechanism with Westat, during the conduct of the study and outside the submitted work. Dr Stockwell reported receiving grants from the CDC to Trustees of Columbia during the conduct of the study. Dr Stenehjem reported receiving grants from the CDC during the conduct of the study and outside the submitted work. Dr Fadel reported receiving grants from the CDC during the conduct of the study and outside the submitted work. Dr Goddard reported receiving grants from the CDC during the conduct of the study. Dr Grisel reported receiving grants from Intermountain Healthcare during the conduct of the study. Dr Arndorfer reported receiving grants from the CDC during the conduct of the study. Dr Ball reported receiving contractual support from the CDC during the conduct of the study. Dr Naleway reported receiving grants from the CDC during the conduct of the study and grants from Pfizer and Vir Biotechnology outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by the CDC through contract 75D30120C07986 to Westat and contract 75D30120C07765 to Kaiser Foundation Hospitals.

Role of the Funder/Sponsor: The CDC was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. The CDC controlled publication decisions.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Additional Contributions: We would like to acknowledge the contributions of the VISION Network CDC: Catherine H. Bozio, PhD, Sue Reynolds, PhD, Lenee Blanton, MPH, Jill Ferdinands, PhD, Palak Patel, MBBS, Eric P. Griggs, MPH, Alexandra Dalton, PhD, Mehiret Wondimu, MPH, Alicia M. Fry, MD, PhD, and Eduardo Azziz-Baumgartner, MD; Westat: Patrick Mitchell, ScD, Duck-Hye Yang, PhD, and Margaret Dunne, MSc; Baylor Scott & White Health: I-Chia Liao, MPH, Deborah Hendricks, BS, Jason Ettlinger, MA, Joel Blais, BTh, Elisa Priest, DrPH, Michael Smith, BS, Spencer Rose, BS, Natalie Settele, MBA, Jennifer Thomas, MS, Muralidhar Jatla, MD, Madhava Beeram, MD, and Alejandro Arroliga, MD; School of Medicine, University of Colorado Anschutz Medical Campus, Health Data Compass: David Mayer, BS, Bryant Doyle, Briana Kille, PhD, and Catia Chavez, MPH; Regenstrief Institute: Ashley Wiensch, MPH and Amy Hancock, MPA, MSES; Center for Health Research, Kaiser Permanente Northwest: Bradley Crane, MS and Padma Dandamudi, MPH; Columbia: Jungmi Han, BS; Health Partners: Malini B. DeSilva, MD, Charlene McEvoy, MD, and Anupam B. Kharbanda, MD; InterMountain: Kristen Dascomb, MD, PhD.

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