Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers.

Importance: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. Objective: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. Design, Setting, and Participants: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. Exposures: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. Main Outcomes and Measures: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. Results: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/µL; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/µL, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). Conclusions and Relevance: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

Effectiveness of 2-Dose BNT162b2 (Pfizer BioNTech) mRNA Vaccine in Preventing SARS-CoV-2 Infection Among Children Aged 5-11 Years and Adolescents Aged 12-15 Years - PROTECT Cohort, July 2021-February 2022.

The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine was recommended by CDC's Advisory Committee on Immunization Practices for persons aged 12-15 years (referred to as adolescents in this report) on May 12, 2021, and for children aged 5-11 years on November 2, 2021 (1-4). Real-world data on vaccine effectiveness (VE) in these age groups are needed, especially because when the B.1.1.529 (Omicron) variant became predominant in the United States in December 2021, early investigations of VE demonstrated a decline in protection against symptomatic infection for adolescents aged 12-15 years and adults* (5). The PROTECT† prospective cohort of 1,364 children and adolescents aged 5-15 years was tested weekly for SARS-CoV-2, irrespective of symptoms, and upon COVID-19-associated illness during July 25, 2021-February 12, 2022. Among unvaccinated participants (i.e., those who had received no COVID-19 vaccine doses) with any laboratory-confirmed SARS-CoV-2 infection, those with B.1.617.2 (Delta) variant infections were more likely to report COVID-19 symptoms (66%) than were those with Omicron infections (49%). Among fully vaccinated children aged 5-11 years, VE against any symptomatic and asymptomatic Omicron infection 14-82 days (the longest interval after dose 2 in this age group) after receipt of dose 2 of the Pfizer-BioNTech vaccine was 31% (95% CI = 9%-48%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. Among adolescents aged 12-15 years, adjusted VE 14-149 days after dose 2 was 87% (95% CI = 49%-97%) against symptomatic and asymptomatic Delta infection and 59% (95% CI = 22%-79%) against Omicron infection. Fully vaccinated participants with Omicron infection spent an average of one half day less sick in bed than did unvaccinated participants with Omicron infection. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Neutralizing Antibody Response to Pseudotype Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Differs Between mRNA-1273 and BNT162b2 Coronavirus Disease 2019 (COVID-19) Vaccines and by History of SARS-CoV-2 Infection.

BACKGROUND: Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited. METHODS: From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models. RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766-1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596-4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186-6926) compared with BNT162b2 vaccine (GMT, 2309; 1825-2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766-31 756) after mRNA vaccine dose 1, without further increase after dose 2. CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Incidence of SARS-CoV-2 infection among COVID-19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January-September 2021.

BACKGROUND: We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. METHODS: We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. RESULTS: Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community. CONCLUSIONS: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

COVID-19 vaccine perceptions and uptake in a national prospective cohort of essential workers.

INTRODUCTION: In a multi-center prospective cohort of essential workers, we assessed knowledge, attitudes, and practices (KAP) by vaccine intention, prior SARS-CoV-2 positivity, and occupation, and their impact on vaccine uptake over time. METHODS: Initiated in July 2020, the HEROES-RECOVER cohort provided socio-demographics and COVID-19 vaccination data. Using two follow-up surveys approximately three months apart, COVID-19 vaccine KAP, intention, and receipt was collected; the first survey categorized participants as reluctant, reachable, or endorser. RESULTS: A total of 4,803 participants were included in the analysis. Most (70%) were vaccine endorsers, 16% were reachable, and 14% were reluctant. By May 2021, 77% had received at least one vaccine dose. KAP responses strongly predicted vaccine uptake, particularly positive attitudes about safety (aOR = 5.46, 95% CI: 1.4-20.8) and effectiveness (aOR = 5.0, 95% CI: 1.3-19.1). Participants' with prior SARS-CoV-2 infection were 22% less likely to believe the COVID-19 vaccine was effective compared with uninfected participants (aOR 0.78, 95% CI: 0.64-0.96). This was even more pronounced in first responders compared with other occupations, with first responders 42% less likely to believe in COVID-19 vaccine effectiveness (aOR = 0.58, 95% CI 0.40-0.84). Between administrations of the two surveys, 25% of reluctant, 56% reachable, and 83% of endorser groups received the COVID-19 vaccine. The reachable group had large increases in positive responses for questions about vaccine safety (10% of vaccinated, 34% of unvaccinated), and vaccine effectiveness (12% of vaccinated, 27% of unvaccinated). DISCUSSION: Our study demonstrates attitudes associated with COVID-19 vaccine uptake and a positive shift in attitudes over time. First responders, despite potential high exposure to SARS-CoV-2, and participants with a history of SARS-CoV-2 infection were more vaccine reluctant. CONCLUSIONS: Perceptions of the COVID-19 vaccine can shift over time. Targeting messages about the vaccine's safety and effectiveness in reducing SARS-CoV-2 virus infection and illness severity may increase vaccine uptake for reluctant and reachable participants.

Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER): Protocol for a Multisite Longitudinal Cohort Study.

BACKGROUND: Workers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. OBJECTIVE: The Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. METHODS: The RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19-like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR-confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. RESULTS: The study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. CONCLUSIONS: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31574.

Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines.

BACKGROUND: Information is limited regarding the effectiveness of the two-dose messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in attenuating coronavirus disease 2019 (Covid-19) when administered in real-world conditions. METHODS: We conducted a prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers. From December 14, 2020, to April 10, 2021, the participants completed weekly SARS-CoV-2 testing by providing mid-turbinate nasal swabs for qualitative and quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis. The formula for calculating vaccine effectiveness was 100% × (1 - hazard ratio for SARS-CoV-2 infection in vaccinated vs. unvaccinated participants), with adjustments for the propensity to be vaccinated, study site, occupation, and local viral circulation. RESULTS: SARS-CoV-2 was detected in 204 participants (5%), of whom 5 were fully vaccinated (≥14 days after dose 2), 11 partially vaccinated (≥14 days after dose 1 and <14 days after dose 2), and 156 unvaccinated; the 32 participants with indeterminate vaccination status (<14 days after dose 1) were excluded. Adjusted vaccine effectiveness was 91% (95% confidence interval [CI], 76 to 97) with full vaccination and 81% (95% CI, 64 to 90) with partial vaccination. Among participants with SARS-CoV-2 infection, the mean viral RNA load was 40% lower (95% CI, 16 to 57) in partially or fully vaccinated participants than in unvaccinated participants. In addition, the risk of febrile symptoms was 58% lower (relative risk, 0.42; 95% CI, 0.18 to 0.98) and the duration of illness was shorter, with 2.3 fewer days spent sick in bed (95% CI, 0.8 to 3.7). CONCLUSIONS: Authorized mRNA vaccines were highly effective among working-age adults in preventing SARS-CoV-2 infection when administered in real-world conditions, and the vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination. (Funded by the National Center for Immunization and Respiratory Diseases and the Centers for Disease Control and Prevention.).

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.

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.