Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalization — Five Veterans Affairs Medical Centers, United States, February 1–August 6, 2021
Weekly / September 17, 2021 / 70(37);1294–1299
On September 10, 2021, this report was posted online as an MMWR Early Release.
Please note:. This report has been corrected.
Kristina L. Bajema, MD1; Rebecca M. Dahl, MPH1; Mila M. Prill, MSPH1; Elissa Meites, MD1; Maria C. Rodriguez-Barradas, MD2,3; Vincent C. Marconi, MD4,5,6; David O. Beenhouwer, MD7,8; Sheldon T. Brown, MD9,10; Mark Holodniy, MD11,12,13; Cynthia Lucero-Obusan, MD11,12; Gilberto Rivera-Dominguez, MD2,3; Rosalba Gomez Morones, MD2,3; Alexis Whitmire, MPH4; Evan B. Goldin7; Steve L. Evener, MPH1,14; Maraia Tremarelli, MSPH1,15; Suxiang Tong, PhD1; Aron J. Hall, DVM1; Stephanie J. Schrag, DPhil1; Meredith McMorrow, MD1; Miwako Kobayashi, MD1; Jennifer R. Verani, MD1*; Diya Surie, MD1*; SUPERNOVA COVID-19; Surveillance Group (View author affiliations)View suggested citation
What is already known about this topic?
mRNA COVID-19 vaccines are effective in preventing severe COVID-19 outcomes, including hospitalization.
What is added by this report?
During February 1–August 6, 2021, vaccine effectiveness among U.S. veterans hospitalized at five Veterans Affairs Medical Centers was 87%. mRNA COVID-19 vaccines remain highly effective, including during periods of widespread circulation of the SARS-CoV-2 B.1.617.2 (Delta) variant. Vaccine effectiveness in preventing COVID-19–related hospitalization was 80% among adults aged ≥65 years compared with 95% among adults aged 18–64 years.
What are the implications for public health practice?
To protect against COVID-19–related hospitalization, all eligible persons should receive COVID-19 vaccination. Additional studies are needed to understand differences in COVID-19 vaccine effectiveness across age groups.
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COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19–associated hospitalizations (1–3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19–associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1–August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19–associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%–91.1%) and was similar before (February 1–June 30) and during (July 1–August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%–87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%–97.8%) among those aged 18–64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19–associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19–related hospitalizations, all eligible persons should receive COVID-19 vaccination.
During February 1–August 6, 2021, adults aged ≥18 years hospitalized at five VAMCs (in Atlanta, Georgia; Bronx, New York; Houston, Texas; Los Angeles, California; and Palo Alto, California) were screened for inclusion in this test-negative case-control assessment.† Patients were eligible for inclusion if they had COVID-19–like illness (i.e., fever, new or worsened cough or shortness of breath, loss of taste or smell, oxygen saturation on room air <94%, requirement for noninvasive ventilation or endotracheal intubation with mechanical ventilation, or chest radiograph or computed tomography pulmonary findings consistent with pneumonia) (1) and a molecular test (reverse transcription–polymerase chain reaction [RT-PCR] or isothermal nucleic acid amplification test) for SARS-CoV-2 performed within 14 days before admission or during the first 72 hours of hospitalization. The first SARS-CoV-2 test within this eligibility period was considered the qualifying test. Patients with COVID-19–like illness who received a positive SARS-CoV-2 test result were included as case-patients, and those with COVID-19–like illness with negative SARS-CoV-2 test results were included as controls.
Electronic health records were reviewed to obtain data on demographic characteristics, underlying medical conditions, presenting illness, SARS-CoV-2 test results, COVID-19 vaccination history, and clinical course during hospitalization. In the Atlanta and Houston VAMCs, COVID-19 vaccination status was further verified through a review of state immunization registries. Full vaccination was defined as receipt of both doses of an mRNA vaccine (Pfizer-BioNTech or Moderna) ≥14 days before the qualifying SARS-CoV-2 test. Participants who received only 1 dose of an mRNA COVID-19 vaccine, 2 mRNA doses with receipt of the second dose <14 days before the qualifying SARS-CoV-2 test, mixed mRNA vaccine products (i.e., a different product for each dose), or the Janssen (Johnson & Johnson) COVID-19 vaccine were excluded from the analysis. Available residual clinical respiratory specimens were collected from case-patients at all sites and sent to CDC for testing. Specimens were tested using CDC’s 2019-Novel Coronavirus RT-PCR Diagnostic Panel§; those with cycle threshold values <33 were submitted for SARS-CoV-2 whole genome sequencing (6). In addition, results from SARS-CoV-2 whole genome sequencing conducted by VAMC laboratories on clinical specimens from Atlanta, Palo Alto, and Bronx VAMCs were also reported to CDC.
Vaccine effectiveness (1 – adjusted odds ratio [aOR] × 100)¶ to prevent COVID-19–associated hospitalization was estimated by using multivariable logistic regression to compare the odds of full vaccination between case-patients and controls. Models were adjusted for VAMC site, admission date and age (with the use of cubic splines), sex, and race/ethnicity. Additional factors were included if they changed the aOR by ≥5% when added individually to the base model. Vaccine effectiveness was compared between subgroups using 95% confidence intervals (CIs). Analyses were conducted using SAS (version 9.4; SAS Institute). Protocols were reviewed and approved by the VAMC Research and Development Committee at each site. The activity was also reviewed by CDC and conducted consistent with applicable federal law and CDC policy.**
During February 1–August 6, 2021, a total of 1,494 hospitalized U.S. veterans met inclusion criteria. After excluding 319 ineligible persons (67 with missing demographic data or vaccination date or product information, 230 who received only 1 dose of mRNA COVID-19 vaccine or 2 doses <14 days before the qualifying SARS-CoV-2 test, one who received mixed mRNA COVID-19 vaccine products, and 21 who received the Janssen COVID-19 vaccine), 388 case-patients and 787 controls were included in the analysis. Among these 1,175 patients, 1,093 (93.0%) were men, the median age was 68 years (interquartile range [IQR] = 59–75 years), 574 (48.9%) were Black, and 93 (7.9%) were Hispanic (Table 1). Prevalence of underlying medical conditions was high and included obesity (46.8%), diabetes (43.8%), atherosclerotic cardiovascular disease (29.2%), and chronic obstructive pulmonary disease (25.4%) (Table 1). Overall, 54 (13.9%) case-patients and 378 (48.0%) controls were fully vaccinated. Among fully vaccinated persons, the median interval between the second COVID-19 vaccine dose and the qualifying SARS-CoV-2 test was 83 days (IQR = 49–129). Among 171 case-patients with SARS-CoV-2 lineage determined,†† Delta became the predominant variant across all sites in July 2021 (Figure).
The adjusted effectiveness of full vaccination in preventing COVID-19–associated hospitalization during the entire evaluation period (February 1–August 6, 2021) was 86.8% (95% CI = 80.4%–91.1%) (Table 2). The adjusted vaccine effectiveness among persons admitted to the hospital before Delta variant predominance (February 1–June 30) (84.1%; 95% CI = 74.1%–90.2%) was similar to vaccine effectiveness during Delta variant predominance (July 1–August 6) (89.3%; 95% CI = 80.1%–94.3%). The estimated vaccine effectiveness among persons aged ≥65 years (79.8%; 95% CI = 67.7%–87.4%) was lower than among persons aged 18–64 years (95.1%; 95% CI = 89.1%–97.8%), and no difference was found between persons who had completed the full vaccination series <90 days (86.1%; 95% CI = 76.5%–91.8%) versus ≥90 days (87.2%; 95% CI = 78.2%–92.5%) before their SARS-CoV-2 test date. Adjusted vaccine effectiveness estimates were also similar for Black (86.9%; 95% CI = 76.9%–92.6%) and White persons (88.1%; 95% CI = 77.4%–93.8%), as well as for Pfizer-BioNTech (83.4%; 95% CI = 74.0%–89.4%) and Moderna vaccines start highlight(91.6%; 95% CI = 83.5%–95.7%)end highlight.
Among U.S. veterans hospitalized at five VAMCs, mRNA vaccines were 86.8% effective in preventing COVID-19–associated hospitalizations and remained highly effective during a period of Delta variant predominance. The mRNA vaccines were effective against COVID-19–associated hospitalization among all age groups, although lower effectiveness (79.8%) was observed among veterans aged ≥65 years. These findings support current evidence that COVID-19 mRNA vaccines are highly effective in preventing COVID-19–associated hospitalization (1–3) and reinforce the importance of vaccination, including among veterans, who are at high risk for COVID-19 hospitalization because they are older and have a higher prevalence of underlying medical conditions compared with persons in the general U.S. population (2,4).
Consistent with national trends,§§ Delta became the predominant SARS-CoV-2 variant in this cohort in July 2021. Protection against COVID-19–associated hospitalization remained high despite the emergence of Delta as the predominant variant in the United States; protection was similar during periods before (February–June 2021; 84.1%) and during (July–August 2021; 89.3%) Delta variant predominance. Recent reports have shown that COVID-19 vaccine protection against SARS-CoV-2 infection is lower in areas with increasing Delta variant transmission (7,8); however, protection against severe disease outcomes, including hospitalization, remains high (7,9).
Although the observed vaccine effectiveness in this study is similar to that reported by other studies measuring protection against COVID-19–associated hospitalization, significantly lower vaccine effectiveness among older adults has not previously been observed (1,2,9). This might be a result of differences in the populations evaluated; periods of vaccine effectiveness assessment, including differences in vaccine coverage, variant circulation, and time since vaccination; and variability in unmeasured confounding. Decreased immunogenicity with increasing age has been reported after vaccination with COVID-19 mRNA vaccines (10). Because one fourth of adults included in this evaluation were aged ≥75 years, age-related differences in immunogenicity might have significantly contributed to lower estimated effectiveness in older persons. Additional evaluations of vaccine effectiveness across age groups, including the relationship between age and duration of protection, are warranted.
The findings in this report are subject to at least four limitations. First, although the five VAMCs included in this assessment were in diverse geographic locations, they are not representative of the entire veteran population or the general U.S. population. Second, despite the inclusion of 1,175 participants, the statistical power was insufficient to detect potential differences in vaccine effectiveness among all subgroups. Third, vaccine effectiveness estimates might be confounded by certain unmeasured behaviors, including mask use or time spent in congregate settings. Finally, the number of veterans in this sample who received the Janssen COVID-19 vaccine was too small to assess the effectiveness of this vaccine in preventing COVID-19–associated hospitalization.
These findings show that the COVID-19 mRNA vaccines remain highly effective for preventing COVID-19–associated hospitalization in this older, racially diverse population of predominantly male U.S. veterans, including during periods of widespread circulation of the SARS-CoV-2 Delta variant. However, vaccine effectiveness was lower among veterans aged ≥65 years than among those aged 18–64 years. Additional evaluations, particularly among older adults with high prevalences of underlying conditions, are important to assess vaccine effectiveness in these populations. COVID-19 vaccination of all eligible persons is essential to prevent COVID-19–associated hospitalizations.
Abirami Balajee; Bettina Bankamp; Daoling Bi; Michael Bowen; Cristina Cardemil; Aaron Curns; Fiona Havers; Lindsay Kim; Brian Lynch; Magdalena Medrzycki; John Michael Metz; Clinton Paden; Krista Queen; Shannon Rogers; Anna Uehara; Nhien Wynn; Jing Zhang; Diagnostics Testing Laboratories, CDC COVID-19 Response Team.
Surveillance Platform for Enteric and Respiratory Infectious Organisms at the VA (SUPERNOVA) COVID-19 Surveillance Group
Ghazal Ahmadi-Izadi, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Joy Burnette, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Rijalda Deovic, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Lauren Epstein, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Amy Hartley, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Elena Morales, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Tehquin Tanner, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Nina Patel, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Ashley Tunson, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Katherine Elliot, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Ilda Graham, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Diki Lama, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Ismael Pena, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Adrienne Perea, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Guerry Anabelle Perez, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Johane Simelane, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Sarah Smith, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Gabriela Tallin, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Amelia Tisi, James J. Peters Veterans Affairs Medical Center, Bronx, New York; Alonso Arellano Lopez, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Miguel Covarrubias Gonzalez, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Bashir Lengi, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Dena Mansouri, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Mariana Vanoye Tamez, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas; Babak Aryanfar, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Ian Lee-Chang, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Chan Jeong, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Anthony Matolek, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Chad Mendoza, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Aleksandra Poteshkina, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Saadia Naeem, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Madhuri Agrawal, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Jessica Lopez, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Theresa Peters, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Geliya Kudryavtseva, Veterans Affairs Palo Alto Health Care System, Palo Alto, California; Jordan Cates, CDC; Jennifer M. Folster, CDC; Anita Kambhampati, CDC; Anna Kelleher, CDC; Yan Li, CDC; Han Jia Ng, CDC; Ying Tao, CDC
Corresponding author: Kristina Bajema, firstname.lastname@example.org.
1CDC COVID-19 Response Team; 2Michael E. DeBakey, Veterans Affairs Medical Center, Houston, Texas; 3Department of Medicine, Baylor College of Medicine, Houston, Texas; 4Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; 5Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; 6Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia; 7Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; 8Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; 9James J. Peters Veterans Affairs Medical Center, Bronx, New York; 10Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; 11Veterans Affairs Palo Alto Health Care System, Palo Alto, California; 12Public Health Surveillance and Research, Department of Veterans Affairs, Washington, DC; 13Department of Medicine, Stanford University, Stanford, California; 14Karna, LLC, Atlanta, Georgia; 15General Dynamics Information Technology, Falls Church, Virginia.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vincent C. Marconi reports research grants from Eli Lilly and Co., Gilead Sciences, and ViiV Healthcare. No other potential conflicts of interest were disclosed.
* These authors contributed equally to this report.
† The test-negative study design included controls with the same clinical syndrome as case-patients to reduce bias from differences in health care–seeking behavior as well as access to testing and care.
** 45 C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
†† Among case-patients with COVID-19–like illness and any COVID-19 vaccination status.
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FIGURE. SARS-CoV-2 whole genome sequencing lineage results* for specimens from veterans aged ≥18 years hospitalized with COVID-19 — five Veterans Affairs Medical Centers,† United States, February 1–August 6, 2021§
* Residual clinical respiratory specimens with SARS-CoV-2 detected by reverse transcription–polymerase chain reaction with a cycle threshold <33 for at least one of two nucleocapsid gene targets were submitted for whole genome sequencing using a combination of Sanger and Illumina sequencing to maximize genome coverage. In addition, sequencing conducted at Veterans Affairs Medical Center laboratories (Clear Labs platform and Thermo Fisher Scientific Ion Torrent next-generation sequencing platform) were also included. The percentage of case-patient specimens sequenced varied over time and was lowest during February–March 2021.
† Atlanta, Georgia; Bronx, New York; Houston, Texas; Los Angeles, California; and Palo Alto, California.
§ Sequencing conducted through July 31, 2021.
Suggested citation for this article: Bajema KL, Dahl RM, Prill MM, et al. Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalization — Five Veterans Affairs Medical Centers, United States, February 1–August 6, 2021. MMWR Morb Mortal Wkly Rep 2021;70:1294–1299. DOI: http://dx.doi.org/10.15585/mmwr.mm7037e3external icon.
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