Abstract
Pregnant women are at higher risk of severe coronavirus disease 2019 (COVID-19) compared with nonpregnant women of reproductive age. During 2023–2024, the Centers for Disease Control and Prevention recommended COVID-19 vaccination for everyone aged 6 months or older, including pregnant women. Using a test-negative design, we assessed the effectiveness of 2023–2024 COVID-19 vaccines against COVID-19–associated emergency department (ED) and urgent care setting encounters among pregnant women aged 18–45 years presenting for care with COVID-19 symptoms from September 2023 to August 2024. Vaccine effectiveness against COVID-19–associated ED and urgent care encounters of one 2023–2024 COVID-19 vaccine dose was 58% (95% CI, 24–77%) among pregnant women and 37% (95% CI, 29–44%) among nonpregnant women of the same age. The 2023–2024 COVID-19 vaccines were associated with a decrease in COVID-19–associated ED and urgent care encounters among pregnant women and nonpregnant women of reproductive age.
Pregnant women have a higher risk of severe coronavirus disease 2019 (COVID-19) than nonpregnant women of reproductive age, which may lead to hospitalization and poor pregnancy outcomes.1–3 During 2023–2024, COVID-19 vaccination was recommended for everyone aged 6 months or older, including pregnant women.4 Studies indicate similar COVID-19 vaccine effectiveness (VE) between pregnant and nonpregnant groups, with vaccination during pregnancy also providing protection for infants.5–7 Continued monitoring is needed to inform whether annual COVID-19 vaccination provides added benefit to pregnant women (regardless of prior vaccination) and whether timing of vaccination during pregnancy affects protection for both mother and infant. The primary objective of this study was to estimate VE of 2023–2024 COVID-19 vaccination against COVID-19–associated emergency department (ED) and urgent care encounters among immunocompetent pregnant and nonpregnant women aged 18–45 years.
METHODS
Using a test-negative design, VE of 2023–2024 COVID-19 vaccines against COVID-19–associated ED and urgent care encounters was evaluated in VISION (Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network), a multistate network of electronic health record data from ED, urgent care, and hospitalization encounters. Inclusion criteria were pregnant and nonpregnant women aged 18–45 years without immunocompromising conditions visiting a participating ED or urgent care clinic during September 2023–August 2024 with COVID-19–like illness documented in their electronic health records and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests conducted within 10 days before or up to 72 hours after the index date (the earlier of either the date of respiratory specimen collection associated with ED or urgent care encounter or the encounter date). The VE and pregnancy-identification methods have been described previously.5,6,8,9 Case patients had a positive SARS-CoV-2 molecular or antigen test result and no positive molecular influenza or respiratory syncytial virus test result. Control patients had a negative molecular test result for SARS-CoV-2 infection and no positive influenza test result, regardless of respiratory syncytial virus test.
Pregnant women were classified as having: 1) received one mRNA or up to two Novavax 2023–2024 COVID-19 vaccine doses at least 7 days before the index date before or during pregnancy; or 2) not received a 2023–2024 COVID-19 vaccine, regardless of vaccine history. Encounters were excluded if any COVID-19 vaccine dose was received less than 7 days before the index date. The unit of analysis was encounter.
We compared the odds of 2023–2024 COVID-19 vaccination among pregnant women by case status, using a multivariable logistic regression model adjusting for age, race and ethnicity, underlying medical conditions (from the following categories: cardiovascular, cerebrovascular, musculoskeletal, neurologic, hematologic, endocrine, renal, and gastrointestinal),10 gestational weeks at encounter, Medicaid status, calendar time, site, and facility location urban–rural classification. To better understand VE estimates among pregnant women, we compared these results (using a Z-test comparing model estimates) with those of nonpregnant women aged 18–45 years in the same VISION sites using the same approach. Vaccine effectiveness was calculated as 1–(adjusted odds ratio)×100%. The odds ratio was adjusted for baseline covariates including race and ethnicity. We included race and ethnicity because vaccine uptake usually varies by race and ethnicity. The unit of analysis was ED or urgent care encounter.
Analyses were conducted using SAS statistical software. The study was approved by the IRBs at participating sites and under a reliance agreement between the Centers for Disease Control and Prevention (CDC) and the Westat IRB. This activity was reviewed by the CDC, deemed not research, and conducted consistent with applicable federal law and CDC policy.11 The study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.
RESULTS
Among 90,873 eligible COVID-19–like illness–associated ED and urgent care encounters among women aged 18–45 years, 741 (14%) pregnant women and 8,611 (10%) nonpregnant women tested positive for SARS-CoV-2 infection (Table 1). The VE of 2023–2024 COVID-19 vaccination was 58% (95% CI, 24–77%, median days since last dose: 77) among pregnant women and 37% (95% CI, 29–44%, median days since last dose: 83) among nonpregnant women (Fig. 1). Estimates of VE were not statistically different between pregnant and nonpregnant women (Z-test P.0.05).
Table 1.
Characteristics of Emergency Department and Urgent Care Encounters Among Immunocompetent Pregnant and Nonpregnant Women With Coronavirus Disease 2019 (COVID-19)–Like Illness by COVID-19 Vaccination Status and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Test Result, September 21, 2023–August 21, 2024
| ED–UC Encounters Among Pregnant Women Aged 18–45 y | ED–UC Encounters Among Nonpregnant Women Aged 18–45 y | |||||||
|---|---|---|---|---|---|---|---|---|
| COVID-19 Vaccination Status [n (Row %)]* | No. Testing Positive for SARS-CoV-2 at ED–UC Encounter [n (Row %)] | COVID-19 Vaccination Status [n (Row %)]* | No. Testing Positive for SARS-CoV-2 at ED–UC Encounter [n (Row %)] | |||||
| Characteristic | Total [n (Column %)] | 2023–2024 Dose | No 2023–2024 Dose | Total [n (Column %)] | 2023–2024 Dose† | No 2023–2024 Dose | ||
| All encounters | 5,360 (100) | 302 (6) | 5,058 (94) | 741 (14) | 85,513 (100) | 6,877 (8) | 78,636 (92) | 8,611 (10) |
| Site 1 | 573 (11) | 67 (12) | 506 (88) | 74 (13) | 10,808 (13) | 1,519 (14) | 9,289 (86) | 1,232 (11) |
| Site 2 | 1,112 (21) | 35 (3) | 1,077 (97) | 202 (18) | 15,909 (19) | 819 (5) | 15,090 (95) | 2,606 (16) |
| Site 3 | 1,552 (29) | 120 (8) | 1,432 (92) | 121 (8) | 20,453 (24) | 2,023 (10) | 18,430 (90) | 1,132 (6) |
| Site 4 | 271 (5) | 20 (7) | 251 (93) | 41 (15) | 5,011 (6) | 705 (14) | 4,306 (86) | 555 (11) |
| Site 5 | 1,173 (22) | 17 (1) | 1,156 (99) | 204 (17) | 18,349 (21) | 463 (3) | 17,886 (97) | 1,400 (8) |
| Site 6 | 679 (13) | 43 (6) | 636 (94) | 99 (15) | 14,983 (18) | 1,348 (9) | 13,635 (91) | 1,686 (11) |
| Age group (y) | ||||||||
| 18–24 | 1,351 (25) | 20 (1) | 1,331 (99) | 188 (14) | 21,413 (25) | 1,145 (5) | 20,268 (95) | 2,033 (9) |
| 25–34 | 3,021 (56) | 173 (6) | 2,848 (94) | 424 (14) | 31,609 (37) | 2,243 (7) | 29,366 (93) | 3,164 (10) |
| 35–45 | 988 (18) | 109 (11) | 879 (89) | 129 (13) | 32,491 (38) | 3,489 (11) | 29,002 (89) | 3,414 (11) |
| Age (y) | 29±6 | 33±5 | 29±6 | 29±6 | 31±8 | 34±8 | 31±8 | 32±8 |
| Race and ethnicity | ||||||||
| Black, non-Hispanic | 717 (13) | 21 (3) | 696 (97) | 101 (14) | 10,871 (13) | 434 (4) | 10,437 (96) | 988 (9) |
| Hispanic | 1,264 (24) | 61 (5) | 1,203 (95) | 154 (12) | 16,770 (20) | 1,094 (7) | 15,676 (93) | 1,630 (10) |
| White, non-Hispanic | 2,515 (47) | 147 (6) | 2,368 (94) | 372 (15) | 46,275 (54) | 4,158 (9) | 42,117 (91) | 4,877 (11) |
| None of the above, non-Hispanic‡ | 567 (11) | 56 (10) | 511 (90) | 80 (14) | 7,510 (9) | 865 (12) | 6,645 (88) | 711 (9) |
| Unknown | 297 (6) | 17 (6) | 280 (94) | 34 (11) | 4,087 (5) | 326 (8) | 3,761 (92) | 405 (10) |
| Most recent vaccine type | ||||||||
| None | 2,076 (39) | 0 (0) | 2,076 (100) | 301 (14) | 29,008 (34) | 0 (0) | 29,008 (100) | 2,729 (9) |
| Original monovalent | 2,545 (47) | 0 (0) | 2,545 (100) | 347 (14) | 41,291 (48) | 0 (0) | 41,291 (100) | 4,452 (11) |
| Bivalent | 437 (8) | 0 (0) | 437 (100) | 61 (14) | 8,337 (10) | 0 (0) | 8,337 (100) | 871 (10) |
| 2023–2024 formula | 302 (6) | 302 (100) | 0 (0) | 32 (11) | 6,877 (8) | 6,877 (100) | 0 (0) | 559 (8) |
| Time since 2023–2024 formula dose (d) | ||||||||
| No 2023–2024 formula dose | 5,058 (94) | NA | 5,058 (100) | 709 (14) | 78,636 (92) | NA | 78,636 (100) | 8,052 (10) |
| 7–59 | 84 (2) | 84 (100) | NA | 7 (8) | 1,772 (2) | 1,772 (100) | NA | 97 (5) |
| 60–119 | 86 (2) | 86 (100) | NA | 4 (5) | 1,845 (2) | 1,845 (100) | NA | 138 (7) |
| 120–179 | 59 (1) | 59 (100) | NA | 2 (3) | 1,462 (2) | 1,462 (100) | NA | 78 (5) |
| 180 or more | 73 (1) | 73 (100) | NA | 19 (26) | 1,798 (2) | 1,798 (100) | NA | 246 (14) |
| Facility urban–rural§ | ||||||||
| Large central or fringe metro | 3,000 (56) | 228 (8) | 2,772 (92) | 383 (13) | 46,893 (55) | 4,704 (10) | 42,189 (90) | 4,296 (9) |
| Medium or small metro | 1,968 (37) | 63 (3) | 1,905 (97) | 287 (15) | 32,196 (38) | 1,826 (6) | 30,370 (94) | 3,596 (11) |
| Micropolitan or non-core | 392 (7) | 11 (3) | 381 (97) | 71 (18) | 6,424 (8) | 347 (5) | 6,077 (95) | 719 (11) |
| Any UMC | ||||||||
| None | 4,692 (88) | 266 (6) | 4,426 (94) | 668 (14) | 70,894 (83) | 5,788 (8) | 65,106 (92) | 7,401 (10) |
| At least 1 | 668 (12) | 36 (5) | 632 (95) | 73 (11) | 14,619 (17) | 1,089 (7) | 13,530 (93) | 1,210 (8) |
| Receiving Medicaid services | ||||||||
| No | 2,963 (55) | 247 (8) | 2,716 (92) | 400 (13) | 49,532 (58) | 5,290 (11) | 44,242 (89) | 5,408 (11) |
| Yes | 1,229 (23) | 39 (3) | 1,190 (97) | 137 (11) | 17,482 (20) | 1,137 (6) | 16,345 (94) | 1,797 (10) |
| Unknown | 1,168 (22) | 16 (1) | 1,152 (99) | 204 (17) | 18,499 (22) | 450 (2) | 18,049 (98) | 1,406 (8) |
| Gestational age at COVID-19–like illness (wk) | 18±11 | 20±11 | 18±11 | 19±10 | NA | NA | NA | NA |
UMC, underlying medical condition; NA, not applicable.
Data are n (%) or mean±SD.
Based on most recent dose received.
Includes one encounter with one 2023–2024 dose of Novavax and one 2023–2024 dose of mRNA vaccine.
Includes American Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, other races not listed, and multiple races. Because of small numbers, these categories were combined.
National Center for Health Statistics urban–rural classification of county where encounter occurred: https://www.cdc.gov/nchs/data-analysis-tools/urban-rural.html.
Fig. 1.
Vaccine effectiveness (VE) of the 2023–2024 coronavirus disease 2019 (COVID-19) vaccine against emergency department and urgent care (ED/UC) encounters among immunocompetent women aged 18–45 years, September 2023–August 2024, VISION (Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network). *Adjusted VE ([1‒odds ratio]×100%) adjusted for age, gestational weeks at encounter (among pregnant patients only), calendar day (all as natural splines), race and ethnicity, presence of any underlying medical conditions, site, and facility location urban–rural classification. IQR, interquartile range; ref, reference category.
Ciesla. 2023–2024 COVID-19 VE in Pregnant Women. Obstet Gynecol 2026.
DISCUSSION
In this large, multi-site study, 2023–2024 COVID-19 vaccination was 58% effective against COVID-19–associated ED and urgent care encounters among women who were pregnant at the time of the encounter. This was not meaningfully different from the VE among nonpregnant women within the same network. Estimated COVID-19 VE in this study is similar to previously reported effectiveness of 2023–2024 COVID-19 vaccination in the general U.S. population12 and to prior estimates of effectiveness of original monovalent or bivalent COVID-19 vaccine given during pregnancy (52%, 95% CI, 29–67%).6 Studies during the Delta and earlier Omicron periods including pregnant women reported higher VE estimates,5,12,13 possibly due to different circulating SARS-CoV-2 sub-variants and population immunity levels during the study periods.
This study has several limitations. First, prior SARS-CoV-2 infection could not be accounted for in this analysis. A national seroprevalence survey found that most U.S. adults had experienced SARS-CoV-2 infection before the 2023–2024 respiratory season.14 Thus, VE estimates should be interpreted as the added benefit of 2023–2024 COVID-19 vaccination. Second, although models adjusted for available confounders, residual confounding may remain, including that related to health care–seeking behaviors. Third, although case patients had COVID-19–like illness and a positive SARS-CoV-2 test result at the time of encounter, the encounter may have been unrelated to COVID-19, which could lower estimated VE. Fourth, due to low vaccination rates in this study, we were unable to perform subgroup analyses (ie, VE by trimester or age group).
The 2023–2024 COVID-19 vaccines conferred protection against COVID-19–associated ED and urgent care encounters among pregnant women and nonpregnant women of reproductive age, providing evidence of continued benefit to both pregnant and nonpregnant women from COVID-19 vaccination during or shortly before pregnancy.
Financial Disclosures
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. During the conduct of the study, all Kaiser Permanente Southern California Division of Research and Kaiser Permanente Northern California Division of Research-affiliated authors reported receiving contractual support from the Centers for Disease Control and Prevention (CDC) via payments made to their respective institutions. Additionally, all authors affiliated with HealthPartners Institute, Intermountain Healthcare, Kaiser Permanente Center for Health Research, Regenstrief Institute, and University of Colorado Anschutz Medical Campus reported receiving contractual support from the CDC during the conduct of the study, via subcontracts from Westat, Inc. with payments made to their respective institutions. Unrelated to the submitted work, the following disclosures were reported from the past 36 months: Gabriela Vazquez-Benitez reports support from Sanofi Pasteur. Nicola P. Klein reports support from Sanofi Pasteur, Merck, Moderna, Pfizer, Seqirus, and GlaxoSmithKline. Shaun J. Grannis reports contracts with National Institutes of Health (NIH) National Center for Advancing Translational Sciences and NIH National Institute of Mental Health. Toan C. Ong received consulting fees from Regenstrief Institute and support for travel from Patient-Centered Outcomes Research Institute (PCORI) and Regenstrief Institute and has a current patent, PCT/US2018/047961. Malini DeSilva reports a contract with Vaccine Safety Datalink with the Center for Excellent in Newcomer Health. Tamara Sheffield is a member of CDC Advisory Committee on Immunization Practices Influenza Vaccine Work Group, chair of Utah Adult Immunization Coalition—volunteer vaccine quality improvement and advocacy group and a member of Utah Department of Health and Human Services Scientific Advisory Committee on Vaccines. Brian E. Dixon reports a contract with Vaccine Safety Datalink Project, Contract No. 75D30122D15424. William Fadel reports a contract with Vaccine Safety Datalink Project, Contract No. 75D30122D15424. Michelle A. Barron was a speaker bureau participant—Innoviva Specialty Therapeutics -Oct 2023. Ousseny Zerbo reports grant number R01AI168373 with the National Institute of Allergy and Infectious Diseases as well as contracts from Moderna and Pfizer. The other authors did not report any potential conflicts of interest.
This study was supported by the Centers for Disease Control and Prevention through contract 75D30121D12779 to Westat Inc. and contract 75D30123C17595 to Kaiser Foundation Hospitals.
This work was supported by the U.S. Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Footnotes
PEER REVIEW HISTORY
Peer reviews and author correspondence are available at http://links.lww.com/AOG/E449.
Each author has confirmed compliance with the journal’s requirements for authorship.
REFERENCES
- 1.Piekos SN, Roper RT, Hwang YM, Sorensen T, Price ND, Hood L, et al. The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study. Lancet Digit Health 2022;4:e95–104. doi: 10.1016/s2589-7500(21)00250-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Marchand G, Patil AS, Masoud AT, Ware K, King A, Ruther S, et al. Systematic review and meta-analysis of COVID-19 maternal and neonatal clinical features and pregnancy outcomes up to June 3, 2021. AJOG Glob Rep 2022;2:100049. doi: 10.1016/j.xagr.2021.100049 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ 2020;370: m3320. doi: 10.1136/bmj.m3320 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines in the United States. Accessed January 16, 2025. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html
- 5.Schrag SJ, Verani JR, Dixon BE, Page JM, Butterfield KA, Gaglani M, et al. 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. JAMA Netw Open 2022;5: e2233273. doi: 10.1001/jamanetworkopen.2022.33273 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Avrich Ciesla A, Lazariu V, Dascomb K, Irving SA, Dixon BE, Gaglani M, et al. Effectiveness of the original monovalent and bivalent COVID-19 vaccines against COVID-19-associated emergency department and urgent care encounters in pregnant persons who were not immunocompromised: VISION network, June 2022-August 2023. Open Forum Infect Dis 2024; 11:ofae481. doi: 10.1093/ofid/ofae481 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Halasa NB, Olson SM, Staat MA, Newhams MM, Price AM, Pannaraj PS, et al. Maternal vaccination and risk of hospitalization for Covid-19 among infants. N Engl J Med 2022;387:109–19. doi: 10.1056/NEJMoa2204399 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Tenforde MW, Weber ZA, Natarajan K, Klein NP, Kharbanda AB, Stenehjem E, et al. Early estimates of bivalent mRNA vaccine effectiveness in preventing COVID-19-associated emergency department or urgent care encounters and hospitalizations among immunocompetent adults - VISION network, nine states, September-November 2022. MMWR Morb Mortal Wkly Rep 2023;71:1637–46. doi: 10.15585/mmwr.mm7153a1 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Link-Gelles R, Weber ZA, Reese SE, Payne AB, Gaglani M, Adams K, et al. Estimates of bivalent mRNA vaccine durability in preventing COVID-19-associated hospitalization and critical illness among adults with and without immunocompromising conditions - VISION network, September 2022-April 2023. MMWR Morb Mortal Wkly Rep 2023;72:579–88. doi: 10.15585/mmwr.mm7221a3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Griggs EP, Mitchell PK, Lazariu V, Gaglani M, McEvoy C, Klein NP, et al. Clinical epidemiology and risk factors for critical outcomes among vaccinated and unvaccinated adults hospitalized with COVID-19—VISION network, 10 states, June 2021–March 2023. Clin Infect Dis 2024;78:338–48. doi: 10.1093/cid/ciad505 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.U.S. Department of Health and Human Services, Office for Human Research Protections. 45 CFR §46. Accessed January 25, 2025. https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html
- 12.Zerbo O, Ray GT, Fireman B, Layefsky E, Goddard K, Ross P, et al. Effectiveness of COVID-19 vaccination during pregnancy by circulating viral variant. AJOG Glob Rep 2023;3:100264. doi: 10.1016/j.xagr.2023.100264 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Guedalia J, Lipschuetz M, Calderon-Margalit R, Cohen SM, Goldman-Wohl D, Kaminer T, et al. Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel. Nat Commun 2022;13: 6961. doi: 10.1038/s41467-022-34605-x [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Centers for Disease Control and Prevention. Antibody seroprevalence. Accessed December 1, 2025. https://www.cdc.gov/covid/php/antibody-seroprevalence/index.html