Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel

33 U.S. Sites, January-March 2021

Tamara Pilishvili, PhD; Katherine E. Fleming-Dutra, MD; Jennifer L. Farrar, MPH; Ryan Gierke, MPH; Nicholas M. Mohr, MD; David A. Talan, MD; Anusha Krishnadasan, PhD; Karisa K. Harland, PhD; Howard A. Smithline, MD; Peter C. Hou, MD; Lilly C. Lee, MD; Stephen C. Lim, MD; Gregory J. Moran, MD; Elizabeth Krebs, MD; Mark Steele, MD; David G. Beiser, MD; Brett Faine, PharmD; John P. Haran, MD, PhD; Utsav Nandi, MD; Walter A. Schrading, MD; Brian Chinnock, MD; Daniel J. Henning, MD; Frank LoVecchio, DO; Joelle Nadle, MPH; Devra Barter, MSc; Monica Brackney, MS; Amber Britton, MPH; Kaytlynn Marceaux-Galli, MPH; Sarah Lim, MBBCh; Erin C. Phipps, DVM; Ghinwa Dumyati, MD; Rebecca Pierce, PhD; Tiffanie M. Markus, PhD; Deverick J. Anderson, MD; Amanda K. Debes, PhD; Michael Lin, MD; Jeanmarie Mayer, MD; Hilary M. Babcock, MD; Nasia Safdar, MD, PhD; Marc Fischer, MD; Rosalyn Singleton, MD; Nora Chea, MD; Shelley S. Magill, MD, PhD; Jennifer Verani, MD; Stephanie Schrag, DPhil


Morbidity and Mortality Weekly Report. 2021;70(20):753-758. 

In This Article

Abstract and Introduction


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 clinics. HCP with the potential for exposure to SARS-CoV-2 through direct patient contact or for indirect exposure (e.g., through infectious materials) were eligible for enrollment. Case-patients and control participants (controls) were identified through routine employee testing performed based on site-specific occupational health practices. HCP with a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen-based test result and at least one COVID-19–like illness symptom§ were enrolled as case-patients, and HCP with a negative SARS-CoV-2 PCR test result, regardless of symptoms, were eligible for enrollment as controls. Controls were frequency matched to case-patients (aiming for a ratio of three controls per case-patient) by site and week of test. HCP who reported having received a positive SARS-CoV-2 PCR or antigen-based test result >60 days earlier (i.e., with a previous SARS-CoV-2 infection) were excluded. Information on demographics, COVID-19–like illness symptoms within 14 days before or after the testing date, and presence of underlying conditions and risk factors for severe COVID-19 were collected through HCP interviews or self-completed surveys. Medical records were reviewed to collect data on SARS-CoV-2 test dates, type, and results and on medical care sought for COVID-19–like illness. Vaccination records, including dates and type of COVID-19 vaccine received, were obtained from occupational health or other verified sources (e.g., vaccine card, state registry, or medical record).

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.

Ten percent of case-patients and 20% of controls had received 1 dose of COVID-19 vaccine ≥14 days before the test date, and 3% of case-patients and 15% of controls had received 2 doses ≥7 days before the test date (Table 2). Among vaccinated persons, 76% of case-patients and 78% of controls received the Pfizer-BioNTech vaccine; the remainder received the Moderna vaccine. The adjusted single-dose VE was 82% (95% CI = 74%–87%) and was similar for both 1-dose sensitivity analyses (before dose 2: VE = 74%, 95% CI = 62%–82%; excluding days 0–2 after dose 2: VE = 78%, 95% CI = 68%–84%). The adjusted 2-dose VE was 94% (95% CI = 87%–97%); effectiveness ≥14 days after the second dose was similar (VE = 90%, 95% CI = 77%–96%).

§Health care personnel are considered symptomatic if one or more of the following signs and symptoms are present 14 days before or after the test date: fever (documented ≥100.4°F [38.0°C] or subjective), 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.
Underlying conditions grouped based on CDC guidelines identifying conditions associated or potentially associated with risk for severe COVID-19 illness.
**This investigation was defined as having met the requirements for public health surveillance as defined in 45 C.F.R. part 46.102(l)(2) 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501 et seq.