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On August 6, 2021, this report was posted as an MMWR Early in 14 states, representing approximately 10% of the U.S.
Release on the MMWR website (https://www.cdc.gov/mmwr). population.† COVID-NET cases were hospitalizations that
Clinical trials of COVID-19 vaccines currently authorized occurred in residents of a designated COVID-NET catch-
for emergency use in the United States (Pfizer-BioNTech, ment area who were admitted within 14 days of a positive
Moderna, and Janssen [Johnson & Johnson]) indicate that SARS-CoV-2 test result. COVID-NET program personnel
these vaccines have high efficacy against symptomatic disease, collected information on COVID-19 vaccination status (vac-
including moderate to severe illness (1–3). In addition to cine product received, number of doses, and administration
clinical trials, real-world assessments of COVID-19 vaccine dates) from state IISs for all sampled COVID-NET cases.§
effectiveness are critical in guiding vaccine policy and building Some sites expanded collection of information on vaccination
vaccine confidence, particularly among populations at higher status to all reported COVID-NET cases, not only sampled
risk for more severe illness from COVID-19, including older cases, which were included for analysis if all cases in a single
adults. To determine the real-world effectiveness of the three month had vaccination status available. Data from 13 sites were
currently authorized COVID-19 vaccines among persons aged included for analysis; one site (Iowa) does not have access to
≥65 years during February 1–April 30, 2021, data on 7,280 the state IIS and cannot collect vaccination data.¶ Population-
patients from the COVID-19–Associated Hospitalization level vaccination coverage was determined using deidentified
Surveillance Network (COVID-NET) were analyzed with vac- person-level COVID-19 vaccination data reported to CDC
cination coverage data from state immunization information by jurisdictions, pharmacies, and federal entities through the
systems (IISs) for the COVID-NET catchment area (approxi- IISs,** Vaccine Administration Management System,†† or
mately 4.8 million persons). Among adults aged 65–74 years, direct data submission.§§
effectiveness of full vaccination in preventing COVID-19– The study was restricted to adults aged ≥65 years and included the
associated hospitalization was 96% (95% confidence interval period February 1–April 30, 2021. The Janssen vaccine was autho-
[CI] = 94%–98%) for Pfizer-BioNTech, 96% (95% CI = 95%– rized for use during the study period beginning March 15, 2021.¶¶
98%) for Moderna, and 84% (95% CI = 64%–93%) for Patients were classified as 1) unvaccinated (no IIS record of vaccina-
Janssen vaccine products. Effectiveness of full vaccination tion), 2) partially vaccinated (1 dose of Moderna or Pfizer-BioNTech
in preventing COVID-19–associated hospitalization among
adults aged ≥75 years was 91% (95% CI = 87%–94%) for † https://www.medrxiv.org/content/10.1101/2021.04.21.21255473v1
§ COVID-NET methodology and sampling scheme: https://www.cdc.gov/
Pfizer-BioNTech, 96% (95% CI = 93%–98%) for Moderna,
coronavirus/2019-ncov/covid-data/covid-net/purpose-methods.html
and 85% (95% CI = 72%–92%) for Janssen vaccine prod- ¶ COVID-NET data included in this analysis were from the following states:
ucts. COVID-19 vaccines currently authorized in the United California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota,
New Mexico, New York, Ohio, Oregon, Tennessee, and Utah.
States are highly effective in preventing COVID-19–associ- ** IISs are confidential, computerized, population-based systems that collect and
ated hospitalizations in older adults. In light of real-world consolidate vaccination data from providers in 64 public health jurisdictions
data demonstrating high effectiveness of COVID-19 vaccines nationwide and can be used to track administered vaccines and measure
vaccination coverage. https://www.cdc.gov/vaccines/covid-19/reporting/
among older adults, efforts to increase vaccination coverage in overview/IT-systems.html
this age group are critical to reducing the risk for COVID-19– †† https://www.cdc.gov/vaccines/covid-19/reporting/vams/program-information.html
§§ https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/about-
related hospitalization.
vaccine-data.html
COVID-NET includes data on laboratory-confirmed ¶¶ Emergency Use Authorization (EUA) for the Janssen (Johnson & Johnson)
COVID-19–associated hospitalizations in 99 U.S. counties vaccine was granted by the Food and Drug Administration on February 26,
2021. EUA was granted for the Pfizer-BioNTech vaccine on December 11,
* These authors contributed equally to this report. 2020, and for the Moderna vaccine on December 18, 2020.
1088 MMWR / August 13, 2021 / Vol. 70 / No. 32 US Department of Health and Human Services/Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report
received ≥14 days before hospitalization or 2 doses, with the second 1 week and 2 weeks before admission, rather than admission
dose received <14 days before hospitalization), or 3) fully vaccinated date, for classification of vaccination status for cases (i.e., add-
(receipt of both doses of Moderna or Pfizer-BioNTech with second ing 7 and 14 days, respectively between last vaccine dose and
dose received ≥14 days before hospitalization or receipt of a single hospital admission date); the same adjustment was included
dose of Janssen ≥14 days before hospitalization). Patients with for population vaccination coverage. Statistical analyses were
only 1 dose of any COVID-19 vaccine received <14 days before conducted using SAS software (version 9.4; SAS Institute). This
hospitalization were excluded. Daily county-level coverage data for activity was reviewed by CDC and was conducted consistent
adults aged 65–74 and ≥75 years in the COVID-NET catchment with applicable federal law and CDC policy.¶¶¶
area were estimated using population denominators from the U.S. During February 1–April 30, 2021, among 7,280 eligible
Census Bureau; vaccination status was classified as described for COVID-NET patients, 5,451 (75%) were unvaccinated, 867
hospitalized cases.*** For vaccine records missing county of resi- (12%) were partially vaccinated, and 394 (5%) were fully vac-
dence, county of vaccine administration was used. cinated; 568 (8%) who received a single vaccine dose <14 days
To estimate vaccine effectiveness and corresponding before hospitalization were excluded from the analysis (Table).
95% CIs, methods were adapted based on previously published Vaccination coverage in the population increased rapidly dur-
literature (4). Poisson regression was used to compare case ing this period among persons aged ≥65 years and varied by age
counts by vaccination status (outcome) and the proportion and vaccine product (Figure 1). Among adults aged ≥65 years
of the population vaccinated and unvaccinated (offset).††† in the COVID-NET catchment area, full vaccination coverage
Data were stratified by age group because of the potential from any of the three authorized vaccines ranged from 0.7%
for confounding by age, and adjusted for COVID-NET site, on February 1, 2021, to 72% on April 30, 2021.
time (number of weeks since the start of the study period as Effectiveness of full vaccination in preventing hospi-
a categorical covariate), and monthly site-specific sampling talization among adults aged 65–74 years was estimated
frequency.§§§ Vaccine effectiveness was calculated as one minus at 96% (95% CI = 94%–98%) for Pfizer-BioNTech,
the exponent of the estimated coefficient of the exposure (vac- 96% (95% CI = 95%–98%) for Moderna, and 84%
cination status) variable. For estimating effectiveness of full (95% CI = 64%–93%) for Janssen vaccine products.
vaccination, partially vaccinated persons were excluded; for Among adults aged ≥75 years, effectiveness of full vaccina-
estimating effectiveness of partial vaccination, fully vaccinated tion was 91% (95% CI = 87%–94%) for Pfizer-BioNTech,
persons were excluded. Vaccine product–specific estimates 96% (95% CI = 93%–98%) for Moderna, and 85% (95%
excluded persons who had received other COVID-19 vaccines. CI = 72%–92%) for Janssen vaccine products (Figure 2).
To account for the interval between infection and hospitaliza- Effectiveness of partial vaccination among adults aged
tion, sensitivity analyses were conducted using a reference date 65–74 years was 84% (95% CI = 76%–89%) for Pfizer-
BioNTech and 91% (95% CI = 87%–93%) for Moderna
*** https://www.cdc.gov/nchs/nvss/bridged_race.htm vaccine products. Among those aged ≥75 years, effectiveness
††† Population vaccine effectiveness is defined as the reduction in disease risk among
vaccinated versus unvaccinated persons in the population. Vaccine effectiveness of partial vaccination was 66% (95% CI = 48%–77%) for
is typically estimated by examining the proportion of persons with disease among Pfizer-BioNTech and 82% (95% CI = 76%–86%) for Moderna
those who are vaccinated and the proportion of persons with disease among vaccine products. Sensitivity analyses accounting for interval
those who are unvaccinated. If these numbers are difficult to measure or estimate
and only case vaccination information is available, then an alternative approach, between infection and hospitalization did not yield notably
called the “screening method,” uses estimates of 1) the proportion of persons different vaccine effectiveness estimates, with point estimates
with disease who are vaccinated and 2) the proportion of persons in the
population who are vaccinated. This analysis applied a variation of the screening
varying by <1% for Pfizer-BioNTech and Moderna vaccine
method through a Poisson regression model, which allows the estimates to models. Point estimates for Janssen COVID-19 vaccine
account for potential confounding. Specifically, the Poisson regression model models varied by <10%, with few cases eligible for inclusion
uses case counts (both vaccinated and unvaccinated) as the outcome, vaccination
status as the exposure variable, and the logarithms of the proportion of vaccinated and wide CIs.
and unvaccinated persons in the population as offsets. The Poisson model includes
the potential confounders time and COVID-NET site as fixed effects because Discussion
vaccination coverage data are available in each time-by-site stratum. A generalized
estimating equation approach with autoregressive correlation structure In this analysis of 7,280 laboratory-confirmed COVID-19–
accommodated daily variations of disease rates and vaccine coverage because this associated cases among hospitalized adults aged ≥65 years, all
study occurred during a time of very rapid change. Finally, the adjusted vaccine three COVID-19 vaccine products currently authorized for
effectiveness estimate was calculated as 1 - exp(β), in which β is the regression
coefficient of the vaccination status exposure variable. use in the United States had high effectiveness in preventing
§§§ Sampling weights were created based on the probability of selection. Weights
were adjusted for nonresponse; adjusted to population catchment totals based ¶¶¶ 45C.F.R. part 46.102(l)(2), 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d);
on combinations of surveillance site, time period of admission, age, sex, and
5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.
race/ethnicity via raking procedures; and trimmed to reduce variability.
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / August 13, 2021 / Vol. 70 / No. 32 1089
Morbidity and Mortality Weekly Report
TABLE. Hospitalized COVID-19 patients aged ≥65 years, by after vaccination (3). The relatively few cases and low popula-
vaccination status and age group (N = 6,712)* — COVID-NET,† tion vaccination coverage with Janssen in this analysis likely
13 states, February 1–April 30, 2021
contributed to the wide CIs for the vaccine effectiveness esti-
No. of cases, by age group (yrs)
mate. In addition, given vaccine prioritization for populations
Vaccination status§,¶ 65–74 ≥75 Total (≥65)
at high risk, older adults receiving the Janssen product were
All patients (any vaccination status) 3,306 3,406 6,712
Unvaccinated patients 2,869 2,582 5,451
more likely to be at lower risk and differ substantially from
Vaccinated patients, by vaccine product
those receiving products available earlier in the vaccine rollout.
Pfizer-BioNTech Other observational studies have demonstrated variability in
Partially vaccinated 188 379 567 the effectiveness of partial vaccination with mRNA vaccines in
Fully vaccinated 73 185 258
Moderna
preventing hospitalization, with point estimates of effectiveness
Partially vaccinated 104 196 300 of 64% to 91% (5,6). Variation in estimates of effectiveness
Fully vaccinated 56 56 112 of partial vaccination between Pfizer-BioNTech and Moderna
Janssen (Johnson & Johnson)** in this analysis might represent confounding from differ-
Fully vaccinated 16 8 24
ences among the persons receiving these products. Residents
Abbreviation: COVID-NET = Coronavirus Disease 2019–Associated Hospitalization
Surveillance Network.
of long-term care facilities (LTCFs) were prioritized early in
* Among 7,280 eligible COVID-NET patients, 568 patients (251 aged 65–74 years the vaccine rollout and were more likely to receive Pfizer-
and 317 aged ≥75 years) who received only 1 dose of any COVID-19 vaccine
<14 days before hospitalization were excluded from analysis.
BioNTech than Moderna.†††† The underlying risk for severe
† COVID-NET data included in this analysis were from the following states: illness from COVID-19 in this medically fragile population
California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, could contribute to lower vaccine effectiveness among LTCF
New Mexico, New York, Ohio, Oregon, Tennessee, and Utah.
§ Partially vaccinated patients received 1 dose of Moderna or Pfizer-BioNTech residents than among the general population of older adults
vaccine ≥14 days before hospitalization or 2 doses, with the second dose and to an apparently lower effectiveness of Pfizer-BioNTech.
received <14 days before hospitalization.
¶ Fully vaccinated patients received both doses of Moderna or Pfizer-BioNTech Moreover, if partial protection increases between the third and
vaccine, with second dose received ≥14 days before hospitalization, or receipt fourth week after receipt of the first dose, it is possible that
of a single dose of Janssen (Johnson & Johnson) vaccine ≥14 days
before hospitalization.
the timing of the second Pfizer-BioNTech and Moderna doses
** The Janssen vaccine was authorized for use after the study began; cases were (21 and 28 days after the first dose, respectively) could affect the
included during March 15–April 30, 2021. observed effectiveness of partial vaccination. Therefore, these
results should not be interpreted as definitive evidence of a dif-
laboratory-confirmed COVID-19–associated hospitalizations. ference in the effectiveness of partial vaccination between the
The effectiveness of full vaccination with mRNA vaccines two mRNA vaccines, but rather as an indication that further
(Pfizer BioNTech and Moderna) was ≥91% and of Janssen evaluation is warranted.
was ≥84% among adults aged ≥65 years. These findings are The findings in this report are subject to at least four limita-
consistent with estimates from other observational studies of tions. First, although adjustments were made for time and site,
the mRNA vaccines and provide an early estimate of the effec- the analysis did not adjust for other potential confounders,
tiveness of Janssen in preventing COVID-19–associated hospi- such as chronic conditions, because person-level data were not
talization (1–3,5). Although the method used in this analysis available for the catchment population. In addition, although
does not account for many important potential confounders the analysis was stratified by age and adjusted for time and site,
and results should be interpreted with caution, taken together, the heterogeneity of disease risk, vaccination coverage within
these findings provide additional evidence that available vaccines each site, and differences in the populations who received
are highly effective in preventing COVID-19–associated hos- different vaccine products might confound estimates of vac-
pitalizations and demonstrate that performance of COVID-19 cine effectiveness. Second, the study period for this analysis
vaccines can be assessed using existing disease surveillance and occurred before the predominance of the B.1.617.2 (Delta)
immunization data. variant; changes in circulating SARS-CoV-2 variants might
This analysis provides an early estimate of the Janssen vac- affect vaccine effectiveness when assessed over time. Third,
cine effectiveness in preventing hospitalization in older adults, persons choosing to receive vaccine later in the rollout might
adding to the limited observational data available assessing have different risk characteristics than do those vaccinated
Janssen vaccine effectiveness.**** These findings are consistent
with clinical trial efficacy data, which found an efficacy of †††† Among COVID-NET patients living in LTCFs, more residents received
76.7% for prevention of moderate to severe disease ≥14 days Pfizer-BioNTech vaccine than received Moderna vaccine, consistent with
state distribution through the federal Pharmacy Partnership for Long-Term
Care Program. https://www.cdc.gov/vaccines/covid-19/long-term-care/
**** https://www.medrxiv.org/content/10.1101/2021.04.27.21256193v1
pharmacy-partnerships-faqs.html
1090 MMWR / August 13, 2021 / Vol. 70 / No. 32 US Department of Health and Human Services/Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report
FIGURE 1. COVID-NET* cases and full vaccination coverage among persons aged 65–74 years (A) and persons aged ≥75 years (B) — 13 states,
February 1–April 30, 2021
70
25
60
50 20
40
15
30
10
20
5
10
0 0
1 8 15 22 1 8 15 22 29 5 12 19 26
Feb Mar Apr
Date
B. Persons aged ≥75 years
110 100
70
30
60
25
50
20
40
15
30
20 10
10 5
0 0
1 8 15 22 1 8 15 22 29 5 12 19 26
Feb Mar Apr
Date
Abbreviation: COVID-NET = Coronavirus Disease 2019–Associated Hospitalization Surveillance Network.
* COVID-NET data included in this analysis were from the following states: California, Colorado, Connecticut, Georgia, Maryland, Michigan, Minnesota, New Mexico,
New York, Ohio, Oregon, Tennessee, and Utah.
earlier and might have experienced differences in access to This analysis found that all COVID-19 vaccines currently
vaccine products by time and location. Finally, this analysis authorized in the United States are highly effective in prevent-
was limited to adults aged ≥65 years, and the results are not ing COVID-19–associated hospitalizations in older adults and
generalizable to younger age groups. also demonstrates the utility of this method in generating a
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / August 13, 2021 / Vol. 70 / No. 32 1091
Morbidity and Mortality Weekly Report
FIGURE 2. Estimates of vaccine effectiveness in preventing COVID-19–associated hospitalization among patients aged ≥65 years for the COVID-NET
catchment area, by vaccine product and age group using the screening method — COVID-NET, 13 states,* February 1–April 30, 2021†
0 10 20 30 40 50 60 70 80 90 100
Acknowledgments
Summary
Gretchen Rothrock, Pam Daily Kirley, Roxanne Archer, Sherry
What is already known about this topic?
Quach, Jeremy Roland, California Emerging Infections Program;
Clinical trials of COVID-19 vaccines currently authorized for Linda Niccolai, Maria Correa, Tessa Carter, Carol Lyons, Daewi
emergency use in the United States (Pfizer-BioNTech, Moderna,
Kim, Connecticut Emerging Infections Program, Yale School of
and Janssen [Johnson & Johnson]) have shown high efficacy in
Public Health; Maya Monroe, Elisabeth Vaeth, Cindy Zerrlaut,
preventing symptomatic (including moderate to severe) COVID-19.
David Blythe, Maryland Department of Health; Rachel Park,
What is added by this report? Michelle Wilson, Maryland Emerging Infections Program, Johns
Among adults aged 65–74 years, effectiveness of full vaccina- Hopkins Bloomberg School of Public Health; Jim Collins, Sam
tion for preventing hospitalization was 96% for Pfizer-BioNTech, Hawkins, Justin Henderson, Shannon Johnson, Lauren Leegwater,
96% for Moderna, and 84% for Janssen COVID-19 vaccines; Sierra Peguies-Khan, Chloe Brown, Michigan Department of Health
among adults aged ≥75 years, effectiveness of full vaccination
and Human Services; Austin Bell, Kalyla Bilski, Erica Bye, Emma
for preventing hospitalization was 91% for Pfizer-BioNTech, 96%
Contestabile, Claire Henrichsen, Emily Holodick, Lisa Nguyen,
for Moderna, and 85% for Janssen COVID-19 vaccines.
Katherine Schleiss, Samantha Siebman, Kristen Ehresmann,
What are the implications for public health practice? Richard Danila, Minnesota Department of Health; Kathy Angeles,
Efforts to increase vaccination coverage are critical to reducing Emily B. Hancock, Yadira Salazar-Sanchez, Meaghan Novi, Sarah A.
the risk for COVID-19–related hospitalization, particularly in Khanlian, Nancy Eisenberg, Melissa Christian, Dominic Rudin,
older adults. Sarah Shrum Davis, New Mexico Emerging Infections Program,
University of New Mexico; Salina Torres, Susan Ropp, New Mexico
relatively rapid assessment of vaccine performance in the setting Department of Health; Kerianne Engesser, Suzanne McGuire, Adam
Rowe, Nancy Spina, New York State Department of Health; Virginia
of high-quality surveillance and vaccine registry data. Efforts
Cafferky, Christina Felsen, Maria Gaitan, RaeAnne Kurtz, Christine
to increase vaccination coverage are critical to reducing the Long, Kevin Popham, Savanah Russ, Marissa Tracy, University of
risk for COVID-19–related hospitalization, particularly in Rochester School of Medicine and Dentistry; Ama Owusu-Dommey,
older adults. Breanna McArdle, Emily Youngers, Public Health Division, Oregon
1092 MMWR / August 13, 2021 / Vol. 70 / No. 32 US Department of Health and Human Services/Centers for Disease Control and Prevention
Morbidity and Mortality Weekly Report
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All authors have completed and submitted the International
Committee of Medical Journal Editors form for disclosure of potential
conflicts of interest. Evan J. Anderson reports grants from Pfizer,
Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and
GSK; personal fees from Sanofi-Pasteur, Pfizer, Medscape, Kentucky
Bioprocessing, Inc, Janssen, outside the submitted work; and his
institution has also received funding from NIH to conduct clinical
trials of Moderna and Janssen COVID-19 vaccines. Sue Kim reports
grants from Michigan Department of Health and Human Services,
during the conduct of the study. William Schaffner reports personal
fees from VBI Vaccines, outside the submitted work. Jessica Shiltz
reports grants from Council for State and Territorial Epidemiologists
during the conduct of the study. No other potential conflicts of
interest were disclosed.
US Department of Health and Human Services/Centers for Disease Control and Prevention MMWR / August 13, 2021 / Vol. 70 / No. 32 1093