Skip to main content
Device Global Header

Subscribe
or Renew

Advanced Search

Editor’s Note: This article was published on September 22, 2021, at NEJM.org.

Original Article

Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel

List of authors.
  • Tamara Pilishvili, Ph.D., M.P.H.,
  • Ryan Gierke, M.P.H.,
  • Katherine E. Fleming-Dutra, M.D.,
  • Jennifer L. Farrar, M.P.H.,
  • Nicholas M. Mohr, M.D.,
  • David A. Talan, M.D.,
  • Anusha Krishnadasan, Ph.D.,
  • Karisa K. Harland, Ph.D.,
  • Howard A. Smithline, M.D.,
  • Peter C. Hou, M.D.,
  • Lilly C. Lee, M.D.,
  • Stephen C. Lim, M.D.,
  • Gregory J. Moran, M.D.,
  • Elizabeth Krebs, M.D.,
  • Mark T. Steele, M.D.,
  • David G. Beiser, M.D.,
  • Brett Faine, Pharm.D.,
  • John P. Haran, M.D., Ph.D.,
  • Utsav Nandi, M.D., M.S.C.I.,
  • Walter A. Schrading, M.D.,
  • Brian Chinnock, M.D.,
  • Daniel J. Henning, M.D., M.P.H.,
  • Frank Lovecchio, D.O., M.P.H.,
  • Jane Lee, M.P.H.,
  • Devra Barter, M.Sc.,
  • Monica Brackney, M.S.,
  • Scott K. Fridkin, M.D.,
  • Kaytlynn Marceaux-Galli, M.P.H.,
  • Sarah Lim, M.B., B.Ch.,
  • Erin C. Phipps, D.V.M., M.P.H.,
  • Ghinwa Dumyati, M.D.,
  • Rebecca Pierce, Ph.D.,
  • Tiffanie M. Markus, Ph.D.,
  • Deverick J. Anderson, M.D., M.P.H.,
  • Amanda K. Debes, Ph.D.,
  • Michael Y. Lin, M.D., M.P.H.,
  • Jeanmarie Mayer, M.D.,
  • Jennie H. Kwon, D.O.,
  • Nasia Safdar, M.D., Ph.D.,
  • Marc Fischer, M.D.,
  • Rosalyn Singleton, M.D.,
  • Nora Chea, M.D.,
  • Shelley S. Magill, M.D., Ph.D.,
  • Jennifer R. Verani, M.D., M.P.H.,
  • and Stephanie J. Schrag, D.Phil.
  • for the Vaccine Effectiveness among Healthcare Personnel Study Team*

Abstract

Background

The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting.

Methods

Download a PDF of the Research Summary.

We conducted a test-negative case–control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19–like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose).

Results

The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer–BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely.

Conclusions

The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.)

Introduction

Digital Object ThumbnailQUICK TAKE
mRNA Covid-19 Vaccination in U.S. Health Care Personnel
 02:11

Health care personnel are at increased risk for exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), through interactions in the workplace related to care and proximity to patients, in addition to household and community interactions.1 In December 2020, two messenger RNA (mRNA) vaccines, the BNT162b2 vaccine from Pfizer–BioNTech and the mRNA-1273 vaccine from Moderna, were approved by the Food and Drug Administration under Emergency Use Authorization for use among persons 16 years of age or older (for the BNT162b2 vaccine) or among those 18 years or older (for the mRNA-1273 vaccine).2-4 The U.S. Advisory Committee on Immunization Practices recommended the prioritization of health care personnel during early-phase distribution of these vaccines5 to ensure that critical services were maintained and that the spread of infection in health care settings was reduced.5 Vaccination of health care personnel in the United States was initiated in December 2020, and by early March 2021, more than half the frontline health care personnel in the United States had been vaccinated with Covid-19 vaccines.6

Phase 3 clinical trials showed the safety and efficacy of the mRNA vaccines,7,8 and early data from observational studies9-11 have supported the clinical trial results. Real-world data on vaccine effectiveness are useful for building on evidence from clinical trials and continuing to inform Covid-19 vaccine policy. The randomized, controlled trials were not powered to evaluate efficacy among persons with chronic illness or among those in racial and ethnic minority groups that have been disproportionately affected by Covid-19.

To evaluate the effectiveness of mRNA vaccines in preventing Covid-19 among health care personnel in the United States, we conducted a multisite, test-negative case–control study involving health care personnel who had been tested for SARS-CoV-2. The interim results of this study showing the effectiveness of the receipt of either mRNA vaccine have been published previously.12 Here, we report the full study results with the extended enrollment through May 2021. We evaluated effectiveness according to vaccine product for partial and complete vaccination and in subgroups defined according to age, race and ethnic group, presence of underlying conditions, estimated level of patient contact, and the time from receipt of two vaccine doses.

Methods

Study Population

Our study population included health care personnel who had been tested for SARS-CoV-2. Participants were enrolled from December 28, 2020 (2 weeks after the introduction of a Covid-19 vaccine), through May 19, 2021, at 33 sites across 25 U.S. states, representing more than 500,000 health care personnel (Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org). The majority (68%) of the participating facilities were acute care hospitals (with or without affiliated outpatient and urgent care clinics), and 32% were long-term care facilities. Covid-19 vaccines were introduced at the participating facilities in December 2020, and the vaccine coverage among health care personnel at these facilities reached 55 to 98% for the receipt of at least one dose of vaccine and 51 to 94% for the receipt of two vaccine doses during the study period.

The study protocol was reviewed by the Centers for Disease Control and Prevention and the institutional review board at each participating medical center and was conducted in accordance with federal laws and institutional policies. The authors vouch for the accuracy and completeness of the data reported and for the fidelity of the study to the protocol.

Study Design

We conducted a test-negative case–control study involving health care personnel, a group that comprised all paid and unpaid health care personnel with the potential for direct exposure to patients or the potential for indirect exposure to infectious materials at the workplace.13 Testing for SARS-CoV-2 was based on occupational health practices at each facility and was leveraged to identify cases and controls for this study. Case participants were defined as health care personnel who had at least one Covid-19–like symptom and a positive result for SARS-CoV-2 on polymerase-chain-reaction (PCR) testing, other nucleic acid amplification testing, or antigen-based testing.14 The index test date (date that the specimen was obtained) for cases was the first SARS-CoV-2–positive test for the episode of Covid-19–like illness for which case participants were enrolled. The illness was defined as symptomatic if the participant had at least one of the following symptoms present within 14 days before or after the index test date: fever (a body temperature documented at ≥38°C or subjective fever), chills, cough (dry or productive), shortness of breath, chest pain or tightness, fatigue or malaise, sore throat, headache, runny nose, congestion, muscle aches, nausea or vomiting, diarrhea, abdominal pain, altered sense of smell or taste, loss of appetite, or red or bruised toes or feet.

Persons who tested negative on PCR or other laboratory-based nucleic acid amplification testing, regardless of symptoms, were eligible for inclusion as controls. Control participants were matched to case participants according to site of enrollment and week of test date. Within any given week and study site, any participants who tested positive for SARS-CoV-2 (cases) and those who tested negative (controls) and agreed to complete a survey or to be interviewed were matched, with a target ratio of three controls per case. Persons with previous infection, defined as a positive SARS-CoV-2 test (on PCR or antigen testing) that had occurred more than 60 days before the index test date, were excluded.

Information on the participants’ demographic characteristics, symptoms of Covid-19–like illness, underlying conditions and risk factors associated with severe Covid-19,15 and medical care received was collected by means of interviews or participant-completed surveys. The interviews and surveys also included information on potential confounders related to workplace and community behaviors. Medical records were reviewed in order to collect information about the SARS-CoV-2 test, including the date, test type, and result, and about the medical care sought during the Covid-19–like illness. Information on Covid-19 vaccination dates and products received was obtained from occupational health clinics, vaccine cards, state registries, or medical records.

Vaccination Status

Vaccination status of the participants was determined at the time of their SARS-CoV-2 test date. Participants were considered to be unvaccinated if they had not received any dose of Covid-19 vaccine as of the test date. We defined the interval from days 0 through 13 after receipt of the first dose as the time before effectiveness from a single dose is expected. We further stratified this interval to evaluate for a potential early effect of the first dose by measuring vaccine effectiveness at 0 to 9 days and at 10 to 13 days after receipt of the first dose, on the basis of the cutoff when vaccine effectiveness after the first dose was measured both in this study and in clinical trials.1,7

The effectiveness of a single vaccine dose was measured from 14 days after receipt of the first dose through 6 days after receipt of the second dose (partially vaccinated). We conducted a sensitivity analysis to evaluate the effectiveness of a single vaccine dose before receipt of the second dose to exclude potential early effects after receipt of the second dose. In an additional sensitivity analysis that evaluated the potential influence of vaccine-related reactions leading to the testing of health care personnel, we excluded participants who had been tested within 0 to 2 days after receipt of the second dose. The effectiveness of two doses of vaccine was measured at 7 days or more after receipt of the second dose (complete vaccination), which was consistent with the Pfizer–BioNTech clinical trial.7 In a sensitivity analysis, we also evaluated the effectiveness of two doses of vaccine at 14 days or more after receipt of the second dose, which was consistent with the Moderna trial.8

Statistical Analysis

We used conditional logistic regression to estimate vaccine effectiveness as 1 minus the matched odds ratio (×100%) for partial vaccination or complete vaccination as compared with no vaccination. We evaluated the influence of age, race and ethnic group, presence of underlying medical conditions or risk factors for severe Covid-19, and other factors related to community and workplace behaviors, such as the use of personal protective equipment and receipt of influenza vaccine during the current respiratory season, as potential confounders for vaccine effectiveness by including each variable with vaccination status in the model and then retaining variables that resulted in a change of more than 10% in the model estimate for vaccination status.

In the final model, we adjusted for age, race and ethnic group, presence of at least one underlying condition or risk factor for severe Covid-19, and close contact with patients with Covid-19 in the workplace or with persons with Covid-19 outside the workplace. We evaluated vaccine effectiveness according to vaccine product and in subgroups defined according to participants’ age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, health care job categories, and clinical case definitions that were consistent with those used in the clinical trials. We examined the adjusted vaccine effectiveness according to 2-week intervals of follow-up after receipt of the second dose (as compared with unvaccinated participants) to assess for waning of vaccine effect. All the statistical analyses were conducted with the use of SAS software, version 9.4 (SAS Institute).

Results

Characteristics of Health Care Personnel

During the study period of December 28, 2020, through May 19, 2021, a total of 109,865 health care personnel were tested across the participating sites; of these persons, 8365 (7.6%) tested positive for SARS-CoV-2. A total of 1482 participants with a positive test and at least one Covid-19–like symptom (cases) and 3449 with a negative test (controls) were enrolled. Among the enrolled health care personnel, 69% worked at acute care hospitals (including emergency departments), 31% in outpatient or specialty clinics, 1% in urgent care clinics, and 1% in long-term care facilities.

Demographic Characteristics of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants) at 33 U.S. Sites, January to May 2021. Workplace and Community Behaviors of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants).

The characteristics of the enrolled participants are shown in Table 1 and Table 2. More than three quarters of the participants (76% of the cases and 75% of the controls) reported having at least one underlying condition associated with an increased risk of severe Covid-19, and no differences were noted in the distribution of individual conditions or risk factors between cases and controls, with the exception of obesity (more common among case participants) and asthma (more common among control participants) (Table S2). We identified 62 cases among pregnant women; the median gestational age at the time of the index test date was 23 weeks (range, 3 to 41). The most common underlying conditions were obesity (in 36% of the case participants and in 31% of the control participants), overweight (in 29% and 28%, respectively), asthma (in 14% and 18%), and hypertension (in 15% and 14%). Only 2% of case participants were hospitalized during their illness; 1% of control participants were hospitalized during a non–Covid-19–related illness. No deaths were reported among the participants included in this study.

A total of 45% of the case participants and 74% of the control participants had received at least one dose of Covid-19 vaccine at any time before the test date. Among vaccinated participants, 78% of the cases and 79% of the controls had received the BNT162b2 vaccine; 21% and 20%, respectively, had received the mRNA-1273 vaccine. The remaining participants had received the ChAdOx1 nCoV-19 vaccine from AstraZeneca (in 2 cases and 1 control) or the Ad26.COV2.S vaccine from Johnson & Johnson (in 8 cases and 28 controls) and were excluded from the analyses of vaccine effectiveness. A higher proportion of control participants than case participants had received one vaccine dose at least 14 days before their test date and had received two doses at least 7 days before their test date.

Estimated Effectiveness of mRNA Vaccines among Health Care Personnel, According to Covid-19 Vaccination Status among Case and Control Participants.

We identified 167 cases among completely vaccinated participants and 140 cases among partially vaccinated participants (Table 3). The characteristics of the completely and partially vaccinated case participants and the unvaccinated case participants are shown in Table S3. Among completely vaccinated case participants, the median length of time after receipt of the second dose to the index test date was 41 days (range, 7 to 165); the median interval between the two doses was 21 days (range, 17 to 42) for the BNT162b2 vaccine and 28 days (range, 24 to 32) for the mRNA-1273 vaccine. The proportion of participants who had severe symptoms or were hospitalized was higher among unvaccinated case participants than among partially or completely vaccinated case participants.

Vaccine Effectiveness

For the period of 0 to 9 days after receipt of the first dose, the vaccine effectiveness was 12.8% (95% confidence interval [CI], −9.4 to 30.5). Vaccine effectiveness at 10 to 13 days after receipt of the first dose was 36.8% (95% CI, 14.8 to 53.1). The adjusted effectiveness for partial vaccination with any vaccine was 79.7% (95% CI, 74.1 to 84.1) and was similar with both the BNT162b2 vaccine (77.6%; 95% CI, 70.9 to 82.7) and the mRNA-1273 vaccine (88.9%; 95% CI, 78.7 to 94.2) (Table 3). Results of sensitivity analyses for partial vaccination were similar when effectiveness was measured before receipt of the second dose (74.0%; 95% CI, 66.1 to 80.1) and when the analyses excluded the period of 0 to 2 days after receipt of the second dose (76.3%; 95% CI, 69.6 to 81.5). The adjusted effectiveness for complete vaccination was 90.4% (95% CI, 87.0 to 92.9) and was similar with either of the two mRNA vaccines; effectiveness that was assessed at 14 days or more after receipt of the second dose also showed similar results (88.9%; 95% CI, 84.7 to 92.0).

Sensitivity analyses that excluded asymptomatic controls resulted in estimates of vaccine effectiveness for partial vaccination of 82.1% (95% CI, 76.6 to 86.3) and for complete vaccination of 90.9% (95% CI, 87.2 to 93.5), results that were similar to those of the primary analysis. The exclusion of case and control participants who reported positive serologic (antibody) test results during the interview did not change the vaccine effectiveness for partial vaccination (79.7%; 95% CI, 74.1 to 84.1) or complete vaccination (90.5%; 95% CI, 87.1 to 93.0).

Estimated Effectiveness of mRNA Vaccines among Health Care Personnel in Subgroups Defined According to Risk Factors, Age Group, and Race and Ethnic Group.

We evaluated vaccine effectiveness according to subgroup and according to clinical case definition (Table 4 and S4). The adjusted effectiveness for partial vaccination or complete vaccination was similar in subgroups defined according to age (<50 years and ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Owing to the limited number of pregnant participants, vaccine effectiveness was estimated in a subgroup that included both partially and completely vaccinated participants (77.1%; 95% CI, 32.2 to 92.2). In a combined group of partially and completely vaccinated participants with immunocompromising conditions, vaccine effectiveness was 39.1% (95% CI, −45.0 to 74.4).

Estimated Adjusted Effectiveness of mRNA Vaccines against Covid-19 among Health Care Personnel According to Follow-up Time after Receipt of the Second Dose.

Vaccine effectiveness was calculated as 1 minus the matched odds ratio for partial or complete vaccination, as compared with no vaccination, and was estimated with the use of a conditional logistic-regression model with accounting for matching according to site of enrollment and week of test date. The effectiveness of messenger RNA (mRNA) vaccines in all categories was estimated in 2-week intervals of follow-up with the use of unvaccinated participants as a reference group. The odds ratio was adjusted for age, race and ethnic group, presence of underlying conditions, and close contact with patients with coronavirus disease 2019 (Covid-19) in the workplace or persons with Covid-19 outside the workplace. 𝙸 bars indicate 95% confidence intervals.

To evaluate evidence of waning of vaccine effect, we estimated effectiveness every 2 weeks during the 14 total weeks of follow-up available immediately after receipt of the second dose (Figure 1). The point estimate of vaccine effectiveness, assessed in 2-week intervals, was highest during weeks 3 and 4 after receipt of the second dose (96.3%; 95% CI, 92.5 to 98.2). The point estimates were lower during weeks 9 through 14, but the 95% confidence intervals were wide and overlapping.

Discussion

In this multisite, test-negative case–control study, we found that both the BNT162b2 and mRNA-1273 vaccines were highly effective against symptomatic Covid-19 among health care personnel. The effectiveness estimates were similar across racial and ethnic groups, among persons with underlying conditions and risk factors associated with an increased risk of severe Covid-19, and in subgroups defined according to various levels of patient contact, including substantial direct contact with patients. Our results showed that the effectiveness of a two-dose regimen with the BNT162b2 vaccine was 89% and that with the mRNA-1273 vaccine was 96%, findings that are consistent with efficacy results from phase 3 trials.7,8

Evidence from postintroduction effectiveness studies has been accruing rapidly. These studies have shown that in a real-world setting, both of these mRNA vaccines work well, and the effectiveness of these vaccines among persons who are completely vaccinated is consistent across observational studies involving different populations16,17 and using different study designs9,18,19 and case definitions.20,21

Although Covid-19 vaccines have been recommended for adults with chronic medical conditions,22 little has been known about the effectiveness of vaccines among adults with individual risk factors for severe outcomes of Covid-19.15 Phase 3 trials showed vaccine efficacy in a group of adults with at least one at-risk condition,7,8 and few observational studies9,23 to date have been powered to evaluate effectiveness among persons with specific underlying conditions. Our study results showed that complete vaccination with mRNA vaccines was effective in adults with more than one risk factor for severe Covid-19; in adults with obesity, hypertension, asthma, or diabetes; and in adults 50 years of age or older. Among health care personnel with immunocompromising conditions, the estimated vaccine effectiveness was low and had confidence intervals that included the null value; these results are consistent with recent studies showing a poor immune response to mRNA vaccines in immunocompromised persons.24,25

Our study showed that mRNA vaccines were effective in pregnant women who were completely or partially vaccinated; the effectiveness among completely vaccinated pregnant women is probably higher than the estimate in our study. Older persons, those with chronic medical conditions, and pregnant women have been recognized during this pandemic as groups at increased risk for severe outcomes of Covid-19,26 and the availability of highly effective vaccines has the potential of reducing mortality and the incidence of hospitalization associated with Covid-19 in these populations.

The effectiveness of partial vaccination, estimated in this study at 78% with the BNT162b2 vaccine and at 89% with the mRNA-1273 vaccine, was higher than the estimates from the respective phase 3 trials.7,8 Although 90% and 94% of the case participants who were included in this study would meet the case definitions of the Pfizer–BioNTech and Moderna phase 3 trials, respectively, our study population was younger (76% of the participants were <50 years of age) and the proportion of participants with chronic underlying conditions was lower than those in the trial populations.7,8 In addition, when the efficacy data for a single dose of the BNT162b2 vaccine were reanalyzed with restriction to cases that occurred at least 14 days after receipt of the first dose (instead of at ≥0 days after receipt of the first dose, as in the initial trial analysis), the efficacy was measured at 92.6%.27 Several cohort studies involving health care personnel have shown effectiveness estimates of partial vaccination with two mRNA vaccines that are consistent with our findings.19,28-33 The high effectiveness of partial vaccination in our study should be interpreted with caution owing to the short window of risk after the receipt of a single dose, given that overall adherence to the recommended administration interval was high (i.e., 21 days for the BNT162b2 vaccine and 28 days for the mRNA-1273 vaccine).34

The effectiveness estimates in our study and in other studies were based on a relatively short follow-up; it is unknown how long this level of protection from either vaccine will last, especially among persons with immunocompromising conditions or among older persons. In this relatively young population of health care personnel, we did not find strong evidence of decreasing effectiveness during the 14 weeks of observation after receipt of the second dose. Although effectiveness estimates during weeks 9 through 14 were lower than the maximum vaccine effectiveness that was observed during weeks 3 and 4, wide and overlapping confidence intervals do not support a conclusion of waning immunity but do warrant longer-term monitoring of vaccine effects.

The findings of this study are subject to limitations. First, the testing of health care personnel for SARS-CoV-2 was based on occupational health practices at each facility. Although participating sites did not report any changes in routine testing practices after the introduction of vaccines, if vaccinated health care personnel were less likely to seek testing than those who were unvaccinated, the vaccine effectiveness could be underestimated. Alternatively, if postvaccination systemic reactions led to vaccinated health care personnel being more likely to seek testing, vaccine effectiveness could be overestimated. A sensitivity analysis that excluded the time window when most postvaccination reactions are expected to occur (0 to 2 days after receipt of the second dose) resulted in estimates of vaccine effectiveness similar to those in the primary analysis. Second, although the study excluded health care personnel with a known history of acute SARS-CoV-2 infection, persons with unknown previous infection could not be excluded. A sensitivity analysis that excluded participants who reported having a positive result for SARS-CoV-2 on serologic testing resulted in estimates of vaccine effectiveness similar to those in the primary analysis, although the number of participants reporting positive serologic tests was small.

Strengths of the study include its large sample size, which allowed for adjustment of confounding and for estimation of vaccine effectiveness in various subgroups of health care personnel, and broad geographic coverage representing the U.S. population. Although we controlled for potential confounders by carefully selecting factors that are common causes of exposure and SARS-CoV-2 infection and, in the final model, selecting from those on the basis of a “change in estimate” approach, there are limitations to this method.35 We had small sample sizes in subgroups of participants with selected underlying conditions, and it will be useful to investigate the reproducibility of these results in future studies. Studies focusing on persons with immunocompromising conditions are needed to understand how well Covid-19 vaccines work in these groups of persons at high risk for severe outcomes of Covid-19. Studies with longer follow-up are necessary for understanding the long-term duration of vaccine effect.

Our study showed that vaccination with either the BNT162b2 or mRNA-1273 vaccine was highly effective in preventing symptomatic Covid-19, a finding that is consistent with the results of phase 3 trials.7,8 Our study also provided additional support to the evidence accruing from observational studies. In this population of health care personnel, vaccine effectiveness was similar among persons with underlying medical conditions or other risk factors for severe Covid-19, including pregnancy; in different subgroups of health care personnel defined according to job category; and in racial and ethnic groups that have been disproportionately affected by the pandemic. The long-term duration of protection and the effectiveness of these vaccines against emerging variants is unknown and should be monitored to indicate whether changes to vaccine composition or vaccine policy are needed.

Funding and Disclosures

Supported by the CDC through agreements or contracts with the following partners: a cooperative agreement with the Emerging Infections Program (www.cdc.gov/ncezid/dpei/eip/index.html), a cooperative agreement (Project PREVENT) with EMERGEncy ID NET (www.emergencyidnet.org), an interagency agreement with the Denali Commission, and contracts with SHEPheRD (www.cdc.gov/hai/research/safehealthcare.html).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. Verani and Schrag contributed equally to this article.

The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). The activity reported in this article was deemed not to be research as defined in 45 Code of Federal Regulations (CFR) 46.102(l), and CDC institutional board review was not required. See, for example, 45 CFR part 46, 21 CFR part 56, 42 U.S. Code section 241(d), 5 U.S. Code section 552a, and 44 U.S. Code §3501 et seq.

This article was published on September 22, 2021, at NEJM.org.

Author Affiliations

From the Covid-19 Response Team, Centers for Disease Control and Prevention (T.P., R.G., K.E.F.-D., J.L.F., M.F., N.C., S.S.M., J.R.V., S.J.S.), and the Georgia Emerging Infections Program and Emory University School of Medicine (S.K.F.) — both in Atlanta; the University of Iowa, Iowa City (N.M.M., D.A.T., K.K.H., B.F.); Olive View and University of California Los Angeles Ronald Reagan Medical Centers, Los Angeles (D.A.T., A.K., G.J.M.), the University of California San Francisco, Fresno (B.C.), and the California Emerging Infections Program, Oakland (J.L.); Baystate Medical Center, Springfield (H.A.S.), Brigham and Women’s Hospital, Boston (P.C.H.), and the University of Massachusetts Medical Center, Worcester (J.P.H.) — all in Massachusetts; Jackson Memorial Hospital, Miami (L.C.L.); University Medical Center, Louisiana State University, New Orleans (S.C.L.); Thomas Jefferson University Hospital, Philadelphia (E.K.); Truman Medical Center, University of Missouri–Kansas City School of Medicine, Kansas City (M.T.S.); the University of Chicago (D.G.B.) and the Department of Medicine, Rush University Medical Center (M.Y.L.) — both in Chicago; the University of Mississippi Medical Center, Jackson (U.N.); the University of Alabama at Birmingham, Birmingham (W.A.S.); the University of Washington, Seattle (D.J.H.); Valleywise Health Medical Center, Arizona State University, Phoenix (F.L.); the Colorado Department of Public Health and Environment, Denver (D.B.); the Connecticut Emerging Infections Program and Yale School of Public Health, New Haven (M.B.); the Maryland Department of Health (K.M.-G.) and Johns Hopkins University School of Medicine (A.K.D.) — both in Baltimore; the Minnesota Emerging Infections Program, Minnesota Department of Health, St. Paul (S.L.); the University of New Mexico, Albuquerque (E.C.P.), and the New Mexico Emerging Infections Program, Santa Fe (E.C.P.); the University of Rochester Medical Center and the New York State–Rochester Emerging Infections Program, Rochester (G.D.); the Public Health Division, Oregon Health Authority, Portland (R.P.); Vanderbilt University Medical Center, Nashville (T.M.M.); the Duke Center for Antimicrobial Stewardship and Infection Prevention, Duke University School of Medicine, Durham, NC (D.J.A.); the University of Utah Veterans Affairs Salt Lake City Health Care System, Salt Lake City (J.M.); Washington University School of Medicine, Division of Infectious Diseases, St. Louis (J.H.K.); the University of Wisconsin–Madison and the William S. Middleton Memorial Veterans Hospital, Madison (N.S.); and the Alaska Native Tribal Health Consortium, Anchorage (R.S.).

Address reprint requests to Dr. Pilishvili at .

A list of the investigators of the Vaccine Effectiveness among Healthcare Personnel Study Team is provided in the Supplementary Appendix, available at NEJM.org.

Supplementary Material

References (35)

  1. 1. Hall VJ, Foulkes S, Saei A, et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study. Lancet 2021;397:1725-1735.

  2. 2. Food and Drug Administration. Pfizer-BioNTech COVID-19 vaccine emergency use authorization. 2020 (https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine).

  3. 3. Food and Drug Administration. Moderna COVID-19 vaccine emergency use authorization. 2020 (https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/Moderna-covid-19-vaccine).

  4. 4. Food and Drug Administration. FDA approves first COVID-19 vaccine. 2021 (https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine).

  5. 5. Dooling K, McClung N, Chamberland M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for allocating initial supplies of COVID-19 vaccine — United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1857-1859.

  6. 6. Kirzinger A, Kearney A, Hamel L, Brodie M. Kaiser Family Foundation/The Washington Post frontline health care workers survey. April 6, 2021 (https://www.kff.org/report-section/kff-washington-post-frontline-health-care-workers-survey-vaccine-intentions/).

  7. 7. Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.

  8. 8. Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384:403-416.

  9. 9. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:1412-1423.

  10. 10. Lumley SF, Rodger G, Constantinides B, et al. An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status. Clin Infect Dis 2021 July 3 (Epub ahead of print).

  11. 11. Shah ASV, Gribben C, Bishop J, et al. Effect of vaccination on transmission of COVID-19: an observational study in healthcare workers and their households. March 21, 2021 (https://www.medrxiv.org/content/10.1101/2021.03.11.21253275v1). preprint.

  12. 12. Pilishvili T, Fleming-Dutra KE, Farrar JL, et al. Interim estimates of vaccine effectiveness of Pfizer-BioNTech and Moderna COVID-19 vaccines among health care personnel — 33 U.S. sites, January–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:753-758.

  13. 13. Centers for Disease Control and Prevention. COVID-19: interim infection prevention and control recommendations for healthcare personnel during the coronavirus disease 2019 (COVID-19) pandemic. 2020 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control-recommendations.html).

  14. 14. Centers for Disease Control and Prevention. Symptoms of COVID-19. February 2021 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html).

  15. 15. Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-19: information for healthcare providers. May 13, 2021 (https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html).

  16. 16. Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 vaccine against the B.1.1.7 and B.1.351 variants. N Engl J Med 2021;385:187-189.

  17. 17. Monitoring of the early impact and effectiveness of COVID-19 vaccination in England. London: Public Health England, March 2021.

  18. 18. Pritchard E, Matthews PC, Stoesser N, et al. Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK’s COVID-19 Infection Survey. April 23, 2021 (https://www.medrxiv.org/content/10.1101/2021.04.22.21255913v1). preprint.

  19. 19. Thompson MG, Burgess JL, Naleway AL, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers — eight U.S. locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:495-500.

  20. 20. Tenforde MW, Olson SM, Self WH, et al. Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years — United States, January–March 2021. MMWR Morb Mortal Wkly Rep 2021;70:674-679.

  21. 21. Goldberg Y, Mandel M, Woodbridge Y, et al. Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: a three-month nationwide experience from Israel. April 24, 2021 (https://www.medrxiv.org/content/10.1101/2021.04.20.21255670v1). preprint.

  22. 22. Dooling K, Marin M, Wallace M, et al. The Advisory Committee on Immunization Practices’ updated interim recommendation for allocation of COVID-19 vaccine — United States, December 2020. MMWR Morb Mortal Wkly Rep 2021;69:1657-1660.

  23. 23. Tenforde MW, Self WH, Naioti EA, et al. Sustained effectiveness of Pfizer–BioNTech and Moderna vaccines against COVID-19 associated hospitalizations among adults — United States, March–July 2021. MMWR Morb Mortal Wkly Rep 2021;70:1156-1162.

  24. 24. Havlin J, Svorcova M, Dvorackova E, et al. Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients. J Heart Lung Transplant 2021;40:754-758.

  25. 25. Rincon-Arevalo H, Choi M, Stefanski A-L, et al. Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients. Sci Immunol 2021;6(60):eabj1031-eabj1031.

  26. 26. Garg S, Kim L, Whitaker M, et al. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 — COVID-NET, 14 states, March 1–30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:458-464.

  27. 27. Skowronski DM, De Serres G. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2021;384:1576-1577.

  28. 28. Angel Y, Spitzer A, Henig O, et al. Association between vaccination with BNT162b2 and incidence of symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. JAMA 2021;325:2457-2465.

  29. 29. Fabiani M, Ramigni M, Gobbetto V, Mateo-Urdiales A, Pezzotti P, Piovesan C. Effectiveness of the Comirnaty (BNT162b2, BioNTech/Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers, Treviso province, Veneto region, Italy, 27 December 2020 to 24 March 2021. Euro Surveill 2021;26(17):2100420-2100420.

  30. 30. Swift MD, Breeher LE, Tande AJ, et al. Effectiveness of mRNA COVID-19 vaccines against SARS-CoV-2 infection in a cohort of healthcare personnel. Clin Infect Dis 2021;26:ciab361-ciab361.

  31. 31. Bouton TC, Lodi S, Turcinovic J, et al. COVID-19 vaccine impact on rates of SARS-CoV-2 cases and post vaccination strain sequences among healthcare workers at an urban academic medical center: a prospective cohort study. March 31, 2021 (https://www.medrxiv.org/content/10.1101/2021.03.30.21254655v1). preprint.

  32. 32. Azamgarhi T, Hodgkinson M, Shah A, et al. BNT162b2 vaccine uptake and effectiveness in UK healthcare workers: a single centre cohort study. Nat Commun 2021;12:3698-3698.

  33. 33. Amit S, Regev-Yochay G, Afek A, Kreiss Y, Leshem E. Early rate reductions of SARS-CoV-2 infection and COVID-19 in BNT162b2 vaccine recipients. Lancet 2021;397:875-877.

  34. 34. Kriss JL, Reynolds LE, Wang A, et al. COVID-19 vaccine second-dose completion and interval between first and second doses among vaccinated persons — United States, December 14, 2020–February 14, 2021. MMWR Morb Mortal Wkly Rep 2021;70:389-395.

  35. 35. VanderWeele TJ. Principles of confounder selection. Eur J Epidemiol 2019;34:211-219.

Citing Articles (4)

    Figures/Media

      Digital Object ThumbnailQUICK TAKE
      mRNA Covid-19 Vaccination in U.S. Health Care Personnel
       02:11

    1. Download a PDF of the Research Summary.

    2. Demographic Characteristics of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants) at 33 U.S. Sites, January to May 2021.*
      Demographic Characteristics of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants) at 33 U.S. Sites, January to May 2021.
    3. Workplace and Community Behaviors of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants).
      Workplace and Community Behaviors of Health Care Personnel Who Tested Positive for SARS-CoV-2 and Had One or More Symptoms of Covid-19–like Illness (Case Participants) and Those Who Tested Negative (Control Participants).
    4. Estimated Effectiveness of mRNA Vaccines among Health Care Personnel, According to Covid-19 Vaccination Status among Case and Control Participants.*
      Estimated Effectiveness of mRNA Vaccines among Health Care Personnel, According to Covid-19 Vaccination Status among Case and Control Participants.
    5. Estimated Effectiveness of mRNA Vaccines among Health Care Personnel in Subgroups Defined According to Risk Factors, Age Group, and Race and Ethnic Group.*
      Estimated Effectiveness of mRNA Vaccines among Health Care Personnel in Subgroups Defined According to Risk Factors, Age Group, and Race and Ethnic Group.
    6. Estimated Adjusted Effectiveness of mRNA Vaccines against Covid-19 among Health Care Personnel According to Follow-up Time after Receipt of the Second Dose.
      Estimated Adjusted Effectiveness of mRNA Vaccines against Covid-19 among Health Care Personnel According to Follow-up Time after Receipt of the Second Dose.

      Vaccine effectiveness was calculated as 1 minus the matched odds ratio for partial or complete vaccination, as compared with no vaccination, and was estimated with the use of a conditional logistic-regression model with accounting for matching according to site of enrollment and week of test date. The effectiveness of messenger RNA (mRNA) vaccines in all categories was estimated in 2-week intervals of follow-up with the use of unvaccinated participants as a reference group. The odds ratio was adjusted for age, race and ethnic group, presence of underlying conditions, and close contact with patients with coronavirus disease 2019 (Covid-19) in the workplace or persons with Covid-19 outside the workplace. 𝙸 bars indicate 95% confidence intervals.

      More Research