Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel — 33 U.S. Sites, January–March 2021

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

On May 14, 2021, this report was posted as an MMWR Early Release on the MMWR website (https: //www.cdc.gov/mmwr).
Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.
A test-negative design case-control study of mRNA COVID-19 VE is underway, with HCP being enrolled at 33 sites across 25 U.S. states; the planned interim analysis presented in this report includes data collected during January-March 2021.* A majority (75%) of enrolled HCP worked at acute care hospitals (including emergency departments), 25% worked in outpatient or specialty clinics, and <1% worked in long-term care facilities and urgent care HCP were defined as unvaccinated if they had not received any COVID-19 vaccine doses or had received their first dose after the test date. The interval of 0-13 days from receipt of the first dose was defined as the time before first dose vaccine effect. The effectiveness of a single dose was measured during the interval from 14 days after the first dose through 6 days after the second dose. Because of the potential for vaccine-related reactions to influence HCP testing behaviors, sensitivity analyses of single-dose VE were conducted 1) excluding participants tested within 0-2 days of receiving the second dose and 2) measuring VE before receiving the second dose. Effectiveness of 2 doses was measured ≥7 days after the receipt of the second dose, consistent with the Pfizer-BioNTech clinical trial procedure (3). Sensitivity analyses measuring 2-dose effectiveness ≥14 days after the second dose were conducted, consistent with the Moderna clinical trial procedure (4). Conditional logistic regression was used to estimate matched odds ratios (mORs) adjusted for age, race/ethnicity, and presence of underlying conditions. VE was estimated as 100% × (1-mOR) for 1 or 2 doses, compared with no doses. Because of the small sample size, analyses could not be stratified by COVID-19 vaccine type. All statistical analyses were conducted using SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.** As of March 18, 2021, 623 case-patients and 1,220 controls had been enrolled. The median ages of case-patients and controls were 38 years (range = 19-69 years) and 37 years (range = 19-76 years), respectively ( Table 1). The majority of HCP (60% of case-patients and 64% of controls) worked in occupational categories with substantial anticipated direct patient contact and were aged 19-49 years (75% and 76%, respectively), female (84% and 82%, respectively), and non-Hispanic White (64% and 70%, respectively). Underlying conditions associated with increased risk for severe COVID-19 were reported by 77% of case-patients and 75% of controls. Case-patients were significantly more likely than controls to have fever (40% versus 23%, p<0.001), cough (56% versus 22%, p<0.001), or shortness of breath (26% versus 7%, p<0.001); 5% of case-patients and 14% of controls reported only mild symptoms (sore throat, headache, runny nose, or congestion; p<0.001); 17% of controls reported no symptoms. Only 12 (2%) case-patients and 10 (1%) controls had severe illness requiring hospitalization, and no deaths occurred in either group.

Discussion
This multisite test-negative design case-control study found that authorized mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) are highly effective against symptomatic COVID-19 among HCP. Effectiveness of a complete 2-dose regimen of these vaccines was estimated to be 94%, consistent with findings from two clinical trials (3,4). Although the case definition applied in this study was broader than that used in both clinical trials (3,4), 93% and 88% of cases included in this study met the respective Pfizer-BioNTech and Moderna trial case definitions. The results are also consistent with findings from an observational study among the general adult population from Israel (5), two cohort studies among HCP from the United Kingdom, † † and recently reported interim results from a U.S. cohort evaluation among HCP and frontline workers (6).

TABLE 1. (Continued) Characteristics of health care personnel case-patients and controls -33 U.S. sites, January-March 2021
Abbreviations: HCP = health care personnel; PCR = polymerase chain reaction. * Case-patients: HCP who received positive SARS-CoV-2 PCR or antigen-based test results and had one or more symptoms of COVID-19-like illness; controls: HCP who received negative SARS-CoV-2 PCR test results. † Includes Asian or Pacific Islander (44 case-patients, 109 controls), American Indian or Alaska Native (23 case-patients, 35 controls), multiple races (5 case-patients, 19 controls), and missing race (5 case-patients, 16 controls). § Substantial patient contact occupational categories: health care providers (physicians, residents, fellows, attending physicians, nurse practitioners, and physician assistants), nurses (registered nurses, other nursing providers including intensive care unit nurses, nurse managers, and midwives), direct patient assistants (licensed practical nurses, certified nursing assistants, patient care technicians and assistants, medical assistants, COVID-19 testers, phlebotomists, home health care providers, emergency medical services providers, and paramedics), and medical therapists (physical therapists; physical therapy assistants; rehabilitation providers; rehabilitation aides; occupational therapists; speech and language pathologists; respiratory therapists; radiology technicians; dental health care providers, including dentists or dental hygienists; and surgical, medical, or emergency technicians). ¶ Moderate patient contact occupational categories: behavioral/social services providers (behavioral health providers [excluding physician psychiatrists], chaplains, social workers and assistants, care coordinators, interpreters, patient registration personnel, health educators, genetic counselors, ambulance dispatchers, dieticians, and research staff members), and environmental services providers (facilities staff members, food services workers, transport workers, patient transport workers, and drivers). ** Minimal patient contact occupational categories: administrative or ward clerks, symptom checkers, telehealth trainers, clinical support staff members, equipment and sterile processing technicians, medical equipment sales personnel, laboratory personnel, and pharmacists. † † Undefined patient contact occupational categories: others who could not be classified into any of the preceding categories and those with missing information. § § Conditions associated with definite or potential increased risk for severe COVID-19 illness as defined by CDC. https://www.cdc.gov/coronavirus/2019-ncov/needextra-precautions/people-with-medical-conditions.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fneed-extra-precautions%2Fgroups-at-higher-risk.html ¶ ¶ Among HCP who reported diabetes mellitus, no case-patients and two controls (<1% of all controls) reported type 1 diabetes, eight case-patients (1% of all case-patients) and nine controls (<1% of all controls) reported type 2 diabetes, and 20 case-patients (3%) and 46 controls (4%) did not specify a diabetes type. *** Immunocompromising conditions include immunosuppression medication (e.g., corticosteroids, chemotherapy, or other immunosuppressive medications), solid organ transplant, hematopoietic stem cell transplant, HIV, thalassemia, or active cancer (current cancer or in treatment or received diagnosis within last 12 months). † † † Smoking includes cigarettes, tobacco, e-cigarettes/vaping, or marijuana use. § § § Statistically significant difference between case-patients and controls; chi-square test, p-value<0.001. ¶ ¶ ¶ Other symptoms include chest pain or tightness, abdominal pain, loss of appetite, red or bruised toes or feet, headache, runny nose, or congestion. **** One person's first dose was Moderna vaccine and second dose was Pfizer-BioNTech vaccine. effectiveness estimates in this and other studies were based on a short follow-up, the duration of this level of protection from a single dose is unknown. The findings in this report are subject to at least four limitations. First, testing for SARS-CoV-2 infection among HCP was based on occupational health practices at each facility, and no changes in routine testing practices were reported after vaccine introduction. If vaccinated HCP were less likely to obtain testing than unvaccinated HCP, the VE might have been underestimated. Alternatively, if postvaccination reactions increased the likelihood that vaccinated HCP would seek testing, the VE might have been overestimated. However, the sensitivity analysis excluding the interval of 0-2 days after receipt of dose 2, the interval during which most postvaccination reactions would be expected to occur, did not significantly change effectiveness estimates. Second, because of the limited sample size, effectiveness by vaccine product, presence of underlying medical conditions, and disease severity could not be estimated. In addition, because of limited statistical power, effectiveness estimates could not be adjusted for other potential confounders, such as use of personal protective equipment, occupational categories, or workplace or community exposures. Third, the VE estimates might not be generalizable to the U.S. adult population because racial/ ethnic minority groups disproportionately affected by COVID-19 and who may have had higher exposure risks in the community were underrepresented in this population, and the overall HCP population was younger than the general U.S. adult population. However, the study's geographic coverage was broad, representing the population of U.S. HCP, and vaccination data were obtained from multiple sources. Finally, although HCP with a known past acute SARS-CoV-2 infection were excluded, those whose previous infection was unknown could not be excluded. Data collection for this study is ongoing and will allow effectiveness to be evaluated by vaccine type and among HCP subgroups.
These interim results demonstrate that complete vaccination with authorized mRNA COVID-19 vaccines is highly effective in preventing symptomatic COVID-19 among HCP,

Summary
What is already known about this topic?
Health care personnel (HCP) are at high risk for COVID-19. The early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP provided an opportunity to examine vaccine effectiveness in a real-world setting.
What is added by this report?
The first U.S. multisite test-negative design vaccine effectiveness study among HCP found a single dose of Pfizer-BioNTech or Moderna COVID-19 vaccines to be 82% effective against symptomatic COVID-19 and 2 doses to be 94% effective.
What are the implications for public health practice?
The mRNA vaccines are highly effective at preventing symptomatic COVID-19 among U.S. HCP. High vaccination coverage among HCP and the general population is critical to prevent COVID-19 in the United States.
supporting the results of phase III trials and additional accruing evidence in recent observational studies. Real-world VE data are critical to guiding evolving COVID-19 vaccine policy. In addition to adherence to recommended infection control and prevention practices, a critical component of controlling the U.S. COVID-19 pandemic and protecting HCP is ensuring high coverage with safe and effective COVID-19 vaccines.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Deverick Anderson is the owner of Infection Control Education for Major Sports, LLC, and reports grants from the Agency for Healthcare Research and Quality and personal fees from UpToDate, outside the submitted work. Ghinwa Dumyati reports grants from Pfizer and personal fees from Roche Diagnostics. Gregory Moran reports grants from I-Mab Biopharma and BeiGene and personal fees from Light AI. Mark Steele reports personal fees from Light AI, during the conduct of the study. No other potential conflicts of interest were disclosed.