Messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccines have been shown to be effective in preventing symptomatic COVID-19 in randomized placebo-controlled Phase III trials ( 1 , 2 ); however, the benefits of these vaccines for preventing asymptomatic and symptomatic SARS-CoV-2 (the virus that causes COVID-19) infection, particularly when administered in real-world conditions, is less well understood. Using prospective cohorts of health care personnel, first responders, and other essential and frontline workers* in eight U.S. locations during December 14, 2020–March 13, 2021, CDC routinely tested for SARS-CoV-2 infections every week regardless of symptom status and at the onset of symptoms consistent with COVID-19–associated illness. Among 3,950 participants with no previous laboratory documentation of SARS-CoV-2 infection, 2,479 (62.8%) received both recommended mRNA doses and 477 (12.1%) received only one dose of mRNA vaccine. † Among unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed by reverse transcription–polymerase chain reaction (RT-PCR) per 1,000 person-days. § In contrast, among fully immunized (≥14 days after second dose) persons, 0.04 infections per 1,000 person-days were reported, and among partially immunized (≥14 days after first dose and before second dose) persons, 0.19 infections per 1,000 person-days were reported. Estimated mRNA vaccine effectiveness for prevention of infection, adjusted for study site, was 90% for full immunization and 80% for partial immunization. These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions. COVID-19 vaccination is recommended for all eligible persons. HEROES-RECOVER ¶ is a network of longitudinal cohorts in eight locations (Phoenix, Tucson, and other areas in Arizona; Miami, Florida; Duluth, Minnesota; Portland, Oregon; Temple, Texas; and Salt Lake City, Utah) that share a common protocol and methods.** Enrollment in this longitudinal study started in July 2020 and included health care personnel, first responders, and other essential and frontline workers who provided written consent. The current vaccine effectiveness analytic study period began on the first day of vaccine administration at study sites (December 14–18, 2020) and ended March 13, 2021. Active surveillance for symptoms consistent with COVID-19–associated illness (defined as fever, chills, cough, shortness of breath, sore throat, diarrhea, muscle aches, or loss of smell or taste) occurred through weekly text messages, e-mails, and direct participant or medical record reports. Participants self-collected a midturbinate nasal swab weekly, regardless of COVID-19–associated illness symptom status and collected an additional nasal swab and saliva specimen at the onset of COVID-19–associated illness. Specimens shipped on cold packs were tested by RT-PCR assay at Marshfield Clinic Laboratory (Marshfield, Wisconsin) to determine SARS-CoV-2 infections (PCR-confirmed infection). Receipt of COVID-19 vaccines was documented by multiple methods: by self-report in electronic surveys, by telephone interviews, and through direct upload of vaccine card images at all sites; records were also extracted from electronic medical records at the Minnesota, Oregon, Texas, and Utah sites. Among 5,077 participants, those with laboratory documentation of SARS-CoV-2 infection before enrollment starting in July 2020 (608) or identified as part of longitudinal surveillance up until the first day of vaccine administration (240) were excluded. Another 279 were excluded because of low participation (i.e., failed to complete surveillance for ≥20% of study weeks and did not contribute COVID-19–associated illness specimens). Overall, 3,950 participants in the vaccine effectiveness analytic sample were analyzed. Hazard ratios were estimated by the Andersen-Gill extension of the Cox proportional hazards model, which accounted for time-varying vaccination status. Hazard ratios of unvaccinated person-days to partial immunization person-days (≥14 days after first dose and before second dose) and to full immunization person-days (≥14 days after second dose) were calculated separately. The 13 person-days between vaccine administration and partial or full immunization were considered excluded at-risk person-time because immunity was considered to be indeterminate. Unadjusted vaccine effectiveness was calculated as 100% × (1−hazard ratio). An adjusted vaccine effectiveness model included study site as a covariate. All analyses were conducted with SAS (version 9.4; SAS Institute). This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy. †† Approximately one half of the participants (52.6%) were from the Arizona study sites (Table 1). Participants included physicians and other clinical leads (primary health care personnel) (21.1%), nurses and other allied health care personnel (33.8%), first responders (21.6%), and other essential and frontline workers (23.5%). The majority of participants were female (62.1%), aged 18–49 years (71.9%), White (86.3%), and non-Hispanic (82.9%) and had no chronic medical conditions (68.9%). Over the 13-week study period, adherence to weekly surveillance reporting and specimen collection was high (median = 100%; interquartile range = 82%–100%). TABLE 1 Characteristics of health care personnel, first responders, and other essential and frontline workers with reverse transcription–polymerase chain reaction (RT-PCR)–confirmed SARS-CoV-2 infections and percentage receiving one or more doses of a messenger RNA (mRNA) COVID-19 vaccine — eight U.S. locations, December 14, 2020–March 13, 2021 Characteristic No. (column %) of participants SARS-CoV-2 infection Unvaccinated Vaccinated with ≥1 dose* No. (row %) p-value† No. (row %) No. (row %) p-value† Total 3,950 (100) 205 (5.2) — 989 (25.0) 2,961 (75.0) — Cohort location Phoenix, Arizona 555 (14.1) 39 (7.0§) 14 days after first dose) of 60% (95% CI = 38%–74%) against PCR-confirmed infection identified by records review in Israel ( 5 ). This finding is also consistent with early descriptive findings of SARS-CoV-2 employee and clinical testing results by mRNA vaccination status in the United States ( 8 , 9 ). The findings in this report are subject to at least three limitations. First, vaccine effectiveness point estimates should be interpreted with caution given the moderately wide CIs attributable in part to the limited number of postimmunization PCR-confirmed infections observed. Second, this also precluded making product-specific vaccine effectiveness estimates and limited the ability to adjust for potential confounders; however, effects were largely unchanged when study site was included in an adjusted vaccine effectiveness model and when adjusted for sex, age, ethnicity, and occupation separately in sensitivity analyses. Finally, self-collection of specimens and delays in shipments could reduce sensitivity of virus detection by PCR ( 10 ); if this disproportionately affected those who received the vaccine (e.g., because of possible vaccine attenuation of virus shedding), vaccine effectiveness would be overestimated. The scientific rigor of these findings is enhanced by its prospective design and the participants’ very high adherence to weekly specimen collection. As the study progresses, viruses will be genetically characterized to examine the viral features of breakthrough infections. Given that there is uncertainty related to the number of days required to develop immunity postvaccination ( 3 – 5 , 7 ), future research examining vaccine effectiveness at different intervals is warranted. These interim vaccine effectiveness findings for both Pfizer-BioNTech’s and Moderna’s mRNA vaccines in real-world conditions complement and expand upon the vaccine effectiveness estimates from other recent studies ( 3 – 5 ) and demonstrate that current vaccination efforts are resulting in substantial preventive benefits among working-age adults. They reinforce CDC’s recommendation of full 2-dose immunization with mRNA vaccines. COVID-19 vaccination is recommended for all eligible persons, which currently varies by location in the United States. Summary What is already known about this topic? Messenger RNA (mRNA) COVID-19 vaccines have been shown to be effective in preventing symptomatic SARS-CoV-2 infection in randomized placebo-controlled Phase III trials. What is added by this report? Prospective cohorts of 3,950 health care personnel, first responders, and other essential and frontline workers completed weekly SARS-CoV-2 testing for 13 consecutive weeks. Under real-world conditions, mRNA vaccine effectiveness of full immunization (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥14 days after first dose but before second dose) was 80%. What are the implications for public health practice? Authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection in real-world conditions. COVID-19 vaccination is recommended for all eligible persons.
