Effectiveness of COVID-19 mRNA Vaccines Against COVID-19–Associated Hospitalization

Five Veterans Affairs Medical Centers, United States, February 1-August 6, 2021

Kristina L. Bajema, MD; Rebecca M. Dahl, MPH; Mila M. Prill, MSPH; Elissa Meites, MD; Maria C. Rodriguez-Barradas, MD; Vincent C. Marconi, MD; David O. Beenhouwer, MD; Sheldon T. Brown, MD; Mark Holodniy, MD; Cynthia Lucero-Obusan, MD; Gilberto Rivera-Dominguez, MD; Rosalba Gomez Morones, MD; Alexis Whitmire, MPH; Evan B. Goldin; Steve L. Evener, MPH; Maraia Tremarelli, MSPH; Suxiang Tong, PhD; Aron J. Hall, DVM; Stephanie J. Schrag, DPhil; Meredith McMorrow, MD; Miwako Kobayashi, MD; Jennifer R. Verani, MD; Diya Surie, MD


Morbidity and Mortality Weekly Report. 2021;70(37):1294-1299. 

In This Article

Abstract and Introduction


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).


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.

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 (91.6%; 95% CI = 83.5%–95.7%)

*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.
§ https://www.fda.gov/media/134922/download
**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.