Research Letter | Infectious Diseases
Incidence of SARS-CoV-2 Infection in Health Care Workers After a Single Dose
of mRNA-1273 Vaccine
Kalpana Gupta, MD, MPH; William J. O’Brien, MS; Pamela Bellino, MA; Katherine Linsenmeyer, MD; Sucheta J. Doshi, MD, MPH;
Robert S. Sprague, MD; Michael E. Charness, MD
Introduction
A 2021 randomized clinical trial1 demonstrated remarkably high efficacy of mRNA-1273 vaccine in
Author affiliations and article information are
listed at the end of this article.
reducing symptomatic SARS-CoV-2 infection after 2 doses administered 28 days apart; however, low
numbers of infection during the first 2 weeks following dose 1 prevented full assessment of early
vaccine efficacy. VA Boston Healthcare System (VABHS) began vaccinating health care workers
(HCWs) during an early winter surge in SARS-CoV-2 infections in Massachusetts.2 A concomitant
large increase in SARS-CoV-2 infections in our workforce provided an opportunity to evaluate the
association between receipt of dose 1 of mRNA-1273 vaccine and SARS-CoV-2 infection.
Methods
For this cohort study, we performed a retrospective survival analysis using a Cox proportional
hazards model with a single time-varying treatment to estimate the hazard ratio (HR) of acquiring
SARS-CoV-2 in vaccinated compared with unvaccinated HCWs. All VABHS clinical and nonclinical
HCWs were included, and the study period was 42 days starting on December 22, 2020, the first day
of vaccine availability. Treatment status changed from unvaccinated to vaccinated on the date of
dose 1, and time prior to vaccination contributed to unvaccinated risk. Dose 2 was administered 28
days after dose 1 (or within 4 days before or after that date). The primary end point was a SARS-CoV-2
reverse transcription–polymerase chain reaction (RT-PCR) positive test.3 All HCWs were offered
mRNA-1273 vaccine in accord with US Centers for Disease Control and Prevention priority guidelines.
Testing was triggered by policy for HCWs with symptoms, exposure, or for mandatory surveillance
on selected units.3 To account for the time required for the development of immunity,4 we calculated
2 additional HRs excluding infections arising in the vaccinated group before days 8 and 15 following
dose 1, respectively. Vaccine effectiveness was calculated as 100% × (1−HR). Analyses were
performed in R version 4.0.4 (R Project for Statistical Computing). P < .05 was considered significant
in 2-sided tests. This study followed Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) reporting guideline for cohort studies. Race was self-classified in human
resources databases and was included for analysis because of racial differences in vaccine hesitancy
and community transmission. Because risk to participants was minimal and the study was deemed a
quality improvement project, informed consent and review were exempted by the VABHS
institutional review board.
Results
The cohort comprised 4028 total HCWs (mean [SD] age, 48.1 [12.1] years; 2473 [61.4%] women;
2682 [66.6%] White, 810 [20.1%] Black) (Table), of which 3367 (83.6%) were vaccinated during the
study period. SARS-CoV-2 infection was identified by RT-PCR in 107 HCWs: 39 vaccinated and 68
unvaccinated. Most infections (75 infections [73.5%]) were symptomatic, and 7 (6.5%) were
identified during routine surveillance (Table). Vaccinated and unvaccinated RT-PCR–positive HCWs
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SARS-CoV-2 Infection in Health Care Workers After a Single Dose of mRNA-1273 Vaccine
did not differ significantly by age, gender, race, proportion of nursing staff, or clinical presentation.
Among the 39 SARS-COV-2–positive vaccinated HCWs, 26 (66.7%) received dose 1 before December
29, 2020. Vaccine clinical effectiveness was 50.3% (95% CI, 23.0%-67.9%) for the entire 42-day
period of follow-up, 77.5% (95% CI, 61.2%-87.0%) for days 8 through 42, and 95.0% (95% CI,
86.0%-98.2%) for days 15 through 42 (Figure). Clinical effectiveness was similar when analysis was
limited to the initial 28 days of study, thereby excluding dose 2 effects.
Discussion
This study demonstrated an association between receipt of mRNA-1273 vaccine and a reduction in
SARS-CoV-2 infection in HCWs beginning 8 days after dose 1. These real-world findings reflect
vaccination solely with mRNA-1273 and are consistent with aggregated data for BNT162b2 and
mRNA-1273 in HCWs.4-6 The first-dose risk reduction of 95% after day 14 highlights the potential for
vaccination with mRNA-1273 to rapidly mitigate surges of vaccine-sensitive SARS-CoV-2 infection
in HCWs.
Table. Demographic and Clinical Characteristics of SARS-CoV-2–Positive HCWs
HCWs, No. (%)
SARS-CoV-2 positive
Total (n = 4028) Vaccinated (n = 39)
Unvaccinated (n = 68)
P valuea
Age, mean (SD), y
48.1 (12.1)
47.9 (17.0)
42.5 (13.2)
.07
Female
2473 (61.4)
21 (53.8)
45 (66.2)
Male
1555 (38.6)
18 (46.2)
23 (33.8)
Black
810 (20.1)
4 (10.3)
14 (20.6)
White
2682 (66.6)
29 (74.4)
50 (73.5)
Other
492 (12)
6 (15.4)
4 (5.9)
1139 (28.3)
15 (38.5)
23 (33.8)
NA
25 (64.1)
50 (73.5)
Characteristics
Demographicb
.21
Abbreviations: HCW, health care worker; NA, not
applicable.
Racec
Nursing staff
Exposure
NA
10 (25.6)
15 (22.1)
Surveillanced
NA
4 (10.3)
3 (4.4)
P values represent comparisons of vaccinated and
unvaccinated SARS-CoV-2–positive HCWs. Age was
compared using a t test, and percentages were
compared using χ2.
b
Demographic data were approximated for the entire
population based on human resources databases
but were not stratified for vaccination status.
c
Race was self-identified from administratively
defined options. Other includes Asian, Native
Hawaiian or Pacific Islander, American Indian or
Alaska Native, and 2 or more races.
d
At least weekly surveillance was conducted on an
average of 400 HCWs during the study period.
.63
Indication for testing
Symptoms
a
.14
.42
Clinical condition at time of positive PCR
Symptomatic
NA
27 (69.2)
51 (75.0)
Presymptomatic
NA
4 (10.3)
4 (5.9)
Asymptomatic
NA
8 (20.5)
13 (11.8)
.68
Figure. Clinical Effectiveness of Dose 1 of mRNA-1273 Vaccine Against SARS-CoV-2 Infection
100
28 d
42 d
Effectiveness, %
80
60
40
20
0
1
2
3
Model
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Hazard ratios were computed for all health care
workers from day 1 (model 1), day 8 (model 2), or day
15 (model 3) after receipt of dose 1 until either day 28
(dark bars) or day 42 (light bars). Error bars indicate
95% CIs. Limiting the analysis to the period before
dose 2 (28 days) did not change the outcome.
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SARS-CoV-2 Infection in Health Care Workers After a Single Dose of mRNA-1273 Vaccine
Limitations of the study include the observational design, the small number of participants from
a single center, and the inability to adjust for confounding characteristics; hence, results may not
generalize to other settings with different demographic characteristics. The period of risk for
infection was slightly later for the vaccinated cohort than the unvaccinated cohort. However, the
study encompassed a sustained period of high community transmission.2 Black HCWs constituted a
higher percentage of the SARS-CoV-2–positive unvaccinated cohort, although these data were not
statistically significant. Finally, these findings address primarily the short-term effects of a single dose
of mRNA-1273 vaccine.
ARTICLE INFORMATION
Accepted for Publication: May 5, 2021.
Published: June 16, 2021. doi:10.1001/jamanetworkopen.2021.16416
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Gupta K
et al. JAMA Network Open.
Corresponding Author: Michael E. Charness, MD, VA Boston Healthcare System, 1400 VFW Pkwy, West Roxbury,
MA 02312 (michael.charness@va.gov).
Author Affiliations: VA Boston Healthcare System, Boston, Massachusetts.
Author Contributions: Drs Charness and Gupta 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.
Concept and design: Gupta, Charness.
Acquisition, analysis, or interpretation of data: O’Brien, Bellino, Linsenmeyer, Doshi, Sprague, Charness.
Drafting of the manuscript: Gupta, Bellino, Charness.
Critical revision of the manuscript for important intellectual content: Gupta, O’Brien, Linsenmeyer, Doshi, Sprague,
Charness.
Statistical analysis: Gupta, O’Brien.
Administrative, technical, or material support: Bellino, Linsenmeyer, Doshi, Sprague.
Supervision: Gupta, Charness.
Conflict of Interest Disclosures: Dr Gupta reported ownership of equity in Moderna and Abbot Pharmaceuticals
in the previous 3 years outside the submitted work. Dr Charness reported ownership of equity in Pfizer currently or
in the past 3 years outside the submitted work. No other disclosures were reported.
Funding/Support: This study was not externally funded. All authors are employees of the US Department of
Veterans Affairs.
Role of the Funder/Sponsor: The Department of Veterans Affairs had no role in the design and conduct of the
study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the
manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We are grateful to Kelly Cho, PhD, for statistical expertise regarding the study design
and Denver Audyatis, BS, for assistance in obtaining demographic information. These contributions were
uncompensated.
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SARS-CoV-2 Infection in Health Care Workers After a Single Dose of mRNA-1273 Vaccine
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