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OBJECTIVE: The goal was to evaluate risk factors for invasive Escherichia coli infections in the first week of life (early onset), focusing on the role of intrapartum antibiotic use. METHODS: We conducted a retrospective case-control study. Between 1997 and 2001, case infants, defined as infants < 7 days of age with E coli isolated from blood or cerebrospinal fluid, were identified in selected counties of California, Georgia, and Connecticut by the Active Bacterial Core Surveillance/Emerging Infections Program Network. Control infants (N = 1212) were identified from a labor and delivery record review of a stratified random sample of live births at the same hospitals in 1998 and 1999. RESULTS: Surveillance identified 132 E coli cases, including 68 ampicillin-resistant cases. The case fatality rate was 16% (21 of 132 cases). Two thirds of case infants were preterm, and 49% (64 of 132 infants) were born at < or = 33 weeks of gestation. Fifty-three percent of case mothers (70 of 132 mothers) received intrapartum antibiotic therapy; 70% of those received ampicillin or penicillin. Low gestational age (< or = 33 weeks), intrapartum fever, and membrane rupture of > or = 18 hours were associated with increased odds of early-onset E coli infection. Results were similar when case subjects were limited to those infected with ampicillin-resistant strains. Exposure to any intrapartum antibiotic treatment, beta-lactam antibiotic treatment, or > or = 4 hours of intrapartum antibiotic therapy was associated with increased odds of E coli infection and ampicillin-resistant infection in univariate analyses. Among preterm infants, intrapartum antibiotic exposure did not remain associated with either outcome in multivariable models. Among term infants, exposure to > or = 4 hours of intrapartum antibiotic therapy was associated with decreased odds of early-onset E coli infection. CONCLUSIONS: Exposure to intrapartum antibiotic therapy did not increase the odds of invasive, early-onset E coli infection. Intrapartum antibiotic therapy was effective in preventing E coli infection only among term infants. [ABSTRACT FROM AUTHOR]

Objective: To assist efforts to improve adult vaccination coverage by characterizing vaccination and infectious disease screening practices of obstetrician-gynecologists.Methods: A written survey of demographics, attitudes, and practices was mailed to 1063 American College of Obstetricians and Gynecologists Fellows, including the Collaborative Ambulatory Research Network (n = 413) and 650 randomly sampled Fellows.Results: Seventy-four percent of Collaborative Ambulatory Research Network members and 44% of nonmembers responded. A majority (Collaborative Ambulatory Research Network members: 60%; nonmembers: 49%) considered themselves primary care providers. Fewer than 60% routinely obtained patient vaccination or infection histories. Most screened prenatal patients for hepatitis B surface antigen (89%) and rubella immunoglobulin G antibody (85%). Sixty-four percent worked in practices that offered at least one vaccine; the most common were rubella (52%) and influenza (50%). Ten percent worked in practices that offered all major vaccines recommended for pregnant or postpartum women. Despite recommendations to provide influenza vaccine to pregnant women during influenza season, only 44% did so; among those who did not, 14% reported a belief that pregnant women do not need influenza vaccine. Provision of vaccine was associated with working in a multispecialty practice (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.6, 4.1) and identifying as a primary care provider (adjusted OR 1.9; 95% CI 1.3, 2.7). The most common reasons for not offering vaccines were cost (44%) and a belief that vaccines should be provided elsewhere (41%).Conclusion: The high proportion of obstetrician-gynecologists who do not offer vaccines or screen for vaccine and infection histories suggests missed opportunities for prevention of maternal and neonatal infections. [ABSTRACT FROM AUTHOR]

Context: Emerging drug resistance threatens the effectiveness of existing therapies for pneumococcal infections. Modifying the dose and duration of antibiotic therapy may limit the spread of resistant pneumococci.Objective: To determine whether short-course, high-dose amoxicillin therapy reduces risk of posttreatment resistant pneumococcal carriage among children with respiratory tract infections.Design and Setting: Randomized trial conducted in an outpatient clinic in Santo Domingo, Dominican Republic, October 1999 through July 2000.Participants: Children aged 6 to 59 months who were receiving antibiotic prescriptions for respiratory tract illness (n = 795).Interventions: Children were randomly assigned to receive 1 of 2 twice-daily regimens of amoxicillin: 90 mg/kg per day for 5 days (n = 398) or 40 mg/kg per day for 10 days (n = 397).Main Outcome Measures: Penicillin-nonsusceptible Streptococcus pneumoniae carriage, assessed in nasopharyngeal specimens collected at days 0, 5, 10, and 28; baseline risk factors for nonsusceptible pneumococcal carriage; and adherence to regimen, compared between the 2 groups.Results: At the day 28 visit, risk of penicillin-nonsusceptible pneumococcal carriage was significantly lower in the short-course, high-dose group (24%) compared with the standard-course group (32%); relative risk (RR), 0.77; 95% confidence interval (CI), 0.60-0.97; P =.03; risk of trimethoprim-sulfamethoxazole nonsusceptibility was also lower in the short-course, high-dose group (RR, 0.77; 95% CI, 0.58-1.03; P =.08). The protective effect of short-course, high-dose therapy was stronger in households with 3 or more children (RR, 0.72; 95% CI, 0.52-0.98). Adherence to treatment was higher in the short-course, high-dose group (82% vs 74%; P =.02).Conclusion: Short-course, high-dose outpatient antibiotic therapy appears promising as an intervention to minimize the impact of antibiotic use on the spread of drug-resistant pneumococci. [ABSTRACT FROM AUTHOR]

This article presents news from the U.S. Centers for Disease Control and Prevention (CDC). In this study, the agency examined perinatal group B streptococcal (GBS) disease after universal screening recommendations were implemented in the U.S. In 2002, the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) issued guidelines that advised universal screening of pregnant women at 35-37 weeks gestation for GBS and the intrapartum antibiotic therapy for GBS carriers. This study found that the preventive measures did lower the incident of early onset GBS in white infants but the rate rose in black infants. The disparity for African Americans appears to be an independent risk factor for the disease.

Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m 2 , caesarean 0.40 kg/m 2 )., (© 2023 World Obesity Federation.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Adam L. Cohen reports travel support from the World Health Organization for attending meetings. Adam L. Hersh reports grants or contracts from the Agency for Health Research and Quality, participation on the National Institutes of Health Data and Safety Monitoring Board, and leadership or fiduciary roles in the Pediatric Infectious Diseases Society. Samir S. Shah reports institutional grant support from the Children’s Hospital Association, textbook royalties from McGraw Hill Education, Wolters Kluwer, and Elsevier, and honoraria from the Society of Hospital Medicine for work as the Editor-in-Chief of the Journal of Hospital Medicine. No other potential conflicts of interest were disclosed.

Background: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the coronavirus disease 2019 (COVID-19) pandemic in the United States are limited., Methods: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as 1 March to 31 December 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014 to February 2020 trends. We conducted secondary analysis of a health care database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic., Results: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated nonpharmaceutical interventions (NPIs). Significant declines were observed across all age and race groups, and surveillance sites for S. pneumoniae and H. influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years., Conclusions: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing., Competing Interests: Presented in part: 12th International Symposium on Pneumococci and Pneumococcal Diseases, Toronto, Canada, 19-23 June., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

On September 1, 2022, bivalent COVID-19 mRNA vaccines, composed of components from the SARS-CoV-2 ancestral and Omicron BA.4/BA.5 strains, were recommended by the Advisory Committee on Immunization Practices (ACIP) to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance (1). Initial recommendations included persons aged ≥12 years (Pfizer-BioNTech) and ≥18 years (Moderna) who had completed at least a primary series of any Food and Drug Administration-authorized or -approved monovalent vaccine ≥2 months earlier (1). On October 12, 2022, the recommendation was expanded to include children aged 5-11 years. At the time of recommendation, immunogenicity data were available from clinical trials of bivalent vaccines composed of ancestral and Omicron BA.1 strains; however, no clinical efficacy data were available. In this study, effectiveness of the bivalent (Omicron BA.4/BA.5-containing) booster formulation against symptomatic SARS-CoV-2 infection was examined using data from the Increasing Community Access to Testing (ICATT) national SARS-CoV-2 testing program.* During September 14-November 11, 2022, a total of 360,626 nucleic acid amplification tests (NAATs) performed at 9,995 retail pharmacies for adults aged ≥18 years, who reported symptoms consistent with COVID-19 at the time of testing and no immunocompromising conditions, were included in the analysis. Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of ≥2 monovalent vaccine doses among persons for whom 2-3 months and ≥8 months had elapsed since last monovalent dose was 30% and 56% among persons aged 18-49 years, 31% and 48% among persons aged 50-64 years, and 28% and 43% among persons aged ≥65 years, respectively. Bivalent mRNA booster doses provide additional protection against symptomatic SARS-CoV-2 in immunocompetent persons who previously received monovalent vaccine only, with relative benefits increasing with time since receipt of the most recent monovalent vaccine dose. Staying up to date with COVID-19 vaccination, including getting a bivalent booster dose when eligible, is critical to maximizing protection against COVID-19 (1)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship., Methods: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build a Bayesian partial latent class model (PLCM) capable of attributing the probable cause of each infant's infection in the ANISA study. The collected risk factors from all mother-child pairs were classified and analysed against the PLCM using bivariate and stepwise logistic multivariable regression modelling to determine risk factors of probable bacterial infection., Results: Among 63 114 infants born, 14 655 were assessed and 6022 had signs of pSBI; of these, 81% (4859) provided blood samples for culture, 71% (4216) provided blood samples for quantitative PCR (qPCR) and 86% (5209) provided respiratory qPCR samples. Risk factors associated with bacterial-attributed infections included: low (relative risk (RR) 1.73, 95% credible interval (CrI) 1.42 to 2.11) and very low birth weight (RR 5.77, 95% CrI 3.73 to 8.94), male sex (RR 1.27, 95% CrI 1.07 to 1.52), breathing problems at birth (RR 2.50, 95% CrI 1.96 to 3.18), premature rupture of membranes (PROMs) (RR 1.27, 95% CrI 1.03 to 1.58) and being in the lowest three socioeconomic status quintiles (first RR 1.52, 95% CrI 1.07 to 2.16; second RR 1.41, 95% CrI 1.00 to 1.97; third RR 1.42, 95% CrI 1.01 to 1.99)., Conclusion: Distinct risk factors: birth weight, male sex, breathing problems at birth and PROM were significantly associated with the development of bacterial sepsis across South Asian community settings, supporting refined clinical discernment and targeted use of antimicrobials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

In April 2021, we assessed mRNA vaccine effectiveness (VE) in the context of a COVID-19 outbreak in a skilled nursing facility. Among 28 cases, genomic sequencing was performed on 4 specimens on 4 different patients, and all were classified by sequence analysis as the Beta (B.1.351) variant. Adjusted VE among residents was 65% (95% confidence interval: 25-84%). These findings underscore the importance of vaccination for prevention of COVID-19 in skilled nursing facilities., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only., Methods: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology., Findings: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding., Interpretation: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions., Funding: The Bill and Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Importance: Pregnant people are at high risk for severe COVID-19 but were excluded from mRNA vaccine trials; data on COVID-19 vaccine effectiveness (VE) are needed., Objective: To evaluate the estimated effectiveness of mRNA vaccination against medically attended COVID-19 among pregnant people during Delta and Omicron predominance., Design, Setting, and Participants: This test-negative, case-control study was conducted from June 2021 to June 2022 in a network of 306 hospitals and 164 emergency department and urgent care (ED/UC) facilities across 10 US states, including 4517 ED/UC encounters and 975 hospitalizations among pregnant people with COVID-19-like illness (CLI) who underwent SARS-CoV-2 molecular testing., Exposures: Two doses (14-149 and ≥150 days prior) and 3 doses (7-119 and ≥120 days prior) of COVID-19 mRNA vaccine (≥1 dose received during pregnancy) vs unvaccinated., Main Outcomes and Measures: Estimated VE against laboratory-confirmed COVID-19-associated ED/UC encounter or hospitalization, based on the adjusted odds ratio (aOR) for prior vaccination; VE was calculated as (1 - aOR) × 100%., Results: Among 4517 eligible CLI-associated ED/UC encounters and 975 hospitalizations, 885 (19.6%) and 334 (34.3%) were SARS-CoV-2 positive, respectively; the median (IQR) patient age was 28 (24-32) years and 31 (26-35) years, 537 (12.0%) and 118 (12.0%) were non-Hispanic Black and 1189 (26.0%) and 240 (25.0%) were Hispanic. During Delta predominance, the estimated VE against COVID-19-associated ED/UC encounters was 84% (95% CI, 69% to 92%) for 2 doses within 14 to 149 days, 75% (95% CI, 5% to 93%) for 2 doses 150 or more days prior, and 81% (95% CI, 30% to 95%) for 3 doses 7 to 119 days prior; estimated VE against COVID-19-associated hospitalization was 99% (95% CI, 96% to 100%), 96% (95% CI, 86% to 99%), and 97% (95% CI, 79% to 100%), respectively. During Omicron predominance, for ED/UC encounters, the estimated VE of 2 doses within 14 to 149 days, 2 doses 150 or more days, 3 doses within 7 to 119 days, and 3 doses 120 or more days prior was 3% (95% CI, -49% to 37%), 42% (95% CI, -16% to 72%), 79% (95% CI, 59% to 89%), and -124% (95% CI, -414% to 2%), respectively; for hospitalization, estimated VE was 86% (95% CI, 41% to 97%), 64% (95% CI, -102% to 93%), 86% (95% CI, 28% to 97%), and -53% (95% CI, -1254% to 83%), respectively., Conclusions and Relevance: In this study, maternal mRNA COVID-19 vaccination, including booster dose, was associated with protection against medically attended COVID-19. VE estimates were higher against COVID-19-associated hospitalization than ED/UC visits and lower against the Omicron variant than the Delta variant. Protection waned over time, particularly during Omicron predominance.

Background: Prisons and jails are high-risk settings for coronavirus disease 2019 (COVID-19). Vaccines may substantially reduce these risks, but evidence is needed on COVID-19 vaccine effectiveness for incarcerated people, who are confined in large, risky congregate settings., Methods: We conducted a retrospective cohort study to estimate effectiveness of messenger RNA (mRNA) vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), against confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among incarcerated people in California prisons from 22 December 2020 through 1 March 2021. The California Department of Corrections and Rehabilitation provided daily data for all prison residents including demographic, clinical, and carceral characteristics, as well as COVID-19 testing, vaccination, and outcomes. We estimated vaccine effectiveness using multivariable Cox models with time-varying covariates, adjusted for resident characteristics and infection rates across prisons., Results: Among 60 707 cohort members, 49% received at least 1 BNT162b2 or mRNA-1273 dose during the study period. Estimated vaccine effectiveness was 74% (95% confidence interval [CI], 64%-82%) from day 14 after first dose until receipt of second dose and 97% (95% CI, 88%-99%) from day 14 after second dose. Effectiveness was similar among the subset of residents who were medically vulnerable: 74% (95% CI, 62%-82%) and 92% (95% CI, 74%-98%) from 14 days after first and second doses, respectively., Conclusions: Consistent with results from randomized trials and observational studies in other populations, mRNA vaccines were highly effective in preventing SARS-CoV-2 infections among incarcerated people. Prioritizing incarcerated people for vaccination, redoubling efforts to boost vaccination, and continuing other ongoing mitigation practices are essential in preventing COVID-19 in this disproportionately affected population., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Importance: Efficacy of 2 doses of the BNT162b2 COVID-19 vaccine (Pfizer-BioNTech) against COVID-19 was high in pediatric trials conducted before the SARS-CoV-2 Omicron variant emerged. Among adults, estimated vaccine effectiveness (VE) of 2 BNT162b2 doses against symptomatic Omicron infection was reduced compared with prior variants, waned rapidly, and increased with a booster., Objective: To evaluate the association of symptomatic infection with prior vaccination with BNT162b2 to estimate VE among children and adolescents during Omicron variant predominance., Design, Setting, and Participants: A test-negative, case-control analysis was conducted using data from 6897 pharmacy-based, drive-through SARS-CoV-2 testing sites across the US from a single pharmacy chain in the Increasing Community Access to Testing platform. This analysis included 74 208 tests from children 5 to 11 years of age and 47 744 tests from adolescents 12 to 15 years of age with COVID-19-like illness who underwent SARS-CoV-2 nucleic acid amplification testing from December 26, 2021, to February 21, 2022., Exposures: Two BNT162b2 doses 2 weeks or more before SARS-CoV-2 testing vs no vaccination for children; 2 or 3 doses 2 weeks or more before testing vs no vaccination for adolescents (who are recommended to receive a booster dose)., Main Outcomes and Measures: Symptomatic infection. The adjusted odds ratio (OR) for the association of prior vaccination and symptomatic SARS-CoV-2 infection was used to estimate VE: VE = (1 - OR) × 100%., Results: A total of 30 999 test-positive cases and 43 209 test-negative controls were included from children 5 to 11 years of age, as well as 22 273 test-positive cases and 25 471 test-negative controls from adolescents 12 to 15 years of age. The median age among those with included tests was 10 years (IQR, 7-13); 61 189 (50.2%) were female, 75 758 (70.1%) were White, and 29 034 (25.7%) were Hispanic/Latino. At 2 to 4 weeks after dose 2, among children, the adjusted OR was 0.40 (95% CI, 0.35-0.45; estimated VE, 60.1% [95% CI, 54.7%-64.8%]) and among adolescents, the OR was 0.40 (95% CI, 0.29-0.56; estimated VE, 59.5% [95% CI, 44.3%-70.6%]). During month 2 after dose 2, among children, the OR was 0.71 (95% CI, 0.67-0.76; estimated VE, 28.9% [95% CI, 24.5%-33.1%]) and among adolescents, the OR was 0.83 (95% CI, 0.76-0.92; estimated VE, 16.6% [95% CI, 8.1%-24.3%]). Among adolescents, the booster dose OR 2 to 6.5 weeks after the dose was 0.29 (95% CI, 0.24-0.35; estimated VE, 71.1% [95% CI, 65.5%-75.7%])., Conclusions and Relevance: Among children and adolescents, estimated VE for 2 doses of BNT162b2 against symptomatic infection was modest and decreased rapidly. Among adolescents, the estimated effectiveness increased after a booster dose.

Vaccine effectiveness (VE) against COVID-19 hospitalization was evaluated among immunocompetent adults (≥18 years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was 96% (95% confidence interval [CI], 93%-98%) among patients with no chronic medical conditions and 83% (95% CI, 76%-88%) among patients with ≥ 3 categories of conditions. VE was similar between those aged 18-64 years versus ≥65 years (P > .05). VE against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing comorbidity burden., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes., Methods: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2., Results: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7-91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI, 79.3-9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8-82.6) than without immunosuppression (91.3%; 95% CI, 85.6-94.8)., Conclusion: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome † (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network § determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits ¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Manjusha Gaglani reports support from Janssen (Johnson & Johnson) for the Baylor Scott & White Health respiratory syncytial virus observational cohort study and uncompensated service as co-chair of the Infectious Diseases and Immunization Committee of the Texas Pediatric Society, Texas Chapter of the American Academy of Pediatrics. Nicola P. Klein reports institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) for unrelated studies, and institutional support from Pfizer for COVID-19 vaccine clinical trials. Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and research funding from Vir Biotechnology. Suchitra Rao reports grant support from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptible individuals between vaccinated and unvaccinated groups. We examined the extent to which biases occur under different scenarios and assessed whether serological testing has the potential to correct this bias. By identifying nonvaccine antibodies, these tests could identify individuals with prior infection. We found that in scenarios with high baseline VE, differential depletion of susceptible individuals created minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE was lower, the bias for leaky vaccines (which reduce individual probability of infection given contact) was larger and should be corrected for by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serological testing, on this critical variable., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2022. This work is written by US Government employees and is in the public domain in the US.)

Importance: Monitoring COVID-19 vaccine performance over time since vaccination and against emerging variants informs control measures and vaccine policies., Objective: To estimate the associations between symptomatic SARS-CoV-2 infection and receipt of BNT162b2, mRNA-1273, and Ad26.COV2.S by day since vaccination before and during Delta variant predominance (pre-Delta period: March 13-May 29, 2021; Delta period: July 18-October 17, 2021)., Design, Setting, and Participants: Test-negative, case-control design with data from 6884 US COVID-19 testing sites in the pharmacy-based Increasing Community Access to Testing platform. This study included 1 634 271 laboratory-based SARS-CoV-2 nucleic acid amplification tests (NAATs) from adults 20 years and older and 180 112 NAATs from adolescents 12 to 19 years old with COVID-19-like illness from March 13 to October 17, 2021., Exposures: COVID-19 vaccination (1 Ad26.COV2.S dose or 2 mRNA doses) 14 or more days prior., Main Outcomes and Measures: Association between symptomatic infection and prior vaccination measured using the odds ratio (OR) from spline-based multivariable logistic regression., Results: The analysis included 390 762 test-positive cases (21.5%) and 1 423 621 test-negative controls (78.5%) (59.9% were 20-44 years old; 9.9% were 12-19 years old; 58.9% were female; 71.8% were White). Among adults 20 years and older, the BNT162b2 mean OR for days 14 to 60 after a second dose (initial OR) was lower during the pre-Delta period (0.10 [95% CI, 0.09-0.11]) than during the Delta period (0.16 [95% CI, 0.16-0.17]) and increased with time since vaccination (per-month change in OR, pre-Delta: 0.04 [95% CI, 0.02-0.05]; Delta: 0.03 [95% CI, 0.02-0.03]). The initial mRNA-1273 OR was 0.05 (95% CI, 0.04-0.05) during the pre-Delta period, 0.10 (95% CI, 0.10-0.11) during the Delta period, and increased with time (per-month change in OR, pre-Delta: 0.02 [95% CI, 0.005-0.03]; Delta: 0.03 [95% CI, 0.03-0.04]). The Ad26.COV2.S initial OR was 0.42 (95% CI, 0.37-0.47) during the pre-Delta period and 0.62 (95% CI, 0.58-0.65) during the Delta period and did not significantly increase with time since vaccination. Among adolescents, the BNT162b2 initial OR during the Delta period was 0.06 (95% CI, 0.05-0.06) among 12- to 15-year-olds, increasing by 0.02 (95% CI, 0.01-0.03) per month, and 0.10 (95% CI, 0.09-0.11) among 16- to 19-year-olds, increasing by 0.04 (95% CI, 0.03-0.06) per month., Conclusions and Relevance: Among adults, the OR for the association between symptomatic SARS-CoV-2 infection and COVID-19 vaccination (as an estimate of vaccine effectiveness) was higher during Delta variant predominance, suggesting lower protection. For mRNA vaccination, the steady increase in OR by month since vaccination was consistent with attenuation of estimated effectiveness over time; attenuation related to time was greater than that related to variant.

CDC recommends that all persons aged ≥12 years receive a booster dose of COVID-19 mRNA vaccine ≥5 months after completion of a primary mRNA vaccination series and that immunocompromised persons receive a third primary dose.* Waning of vaccine protection after 2 doses of mRNA vaccine has been observed during the period of the SARS-CoV-2 B.1.617.2 (Delta) variant predominance † (1-5), but little is known about durability of protection after 3 doses during periods of Delta or SARS-CoV-2 B.1.1.529 (Omicron) variant predominance. A test-negative case-control study design using data from eight VISION Network sites § examined vaccine effectiveness (VE) against COVID-19 emergency department/urgent care (ED/UC) visits and hospitalizations among U.S. adults aged ≥18 years at various time points after receipt of a second or third vaccine dose during two periods: Delta variant predominance and Omicron variant predominance (i.e., periods when each variant accounted for ≥50% of sequenced isolates). ¶ Persons categorized as having received 3 doses included those who received a third dose in a primary series or a booster dose after a 2 dose primary series (including the reduced-dosage Moderna booster). The VISION Network analyzed 241,204 ED/UC encounters** and 93,408 hospitalizations across 10 states during August 26, 2021-January 22, 2022. VE after receipt of both 2 and 3 doses was lower during the Omicron-predominant than during the Delta-predominant period at all time points evaluated. During both periods, VE after receipt of a third dose was higher than that after a second dose; however, VE waned with increasing time since vaccination. During the Omicron period, VE against ED/UC visits was 87% during the first 2 months after a third dose and decreased to 66% among those vaccinated 4-5 months earlier; VE against hospitalizations was 91% during the first 2 months following a third dose and decreased to 78% ≥4 months after a third dose. For both Delta- and Omicron-predominant periods, VE was generally higher for protection against hospitalizations than against ED/UC visits. All eligible persons should remain up to date with recommended COVID-19 vaccinations to best protect against COVID-19-associated hospitalizations and ED/UC visits., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein reports institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) for unrelated studies and institutional support from Pfizer for a COVID-19 vaccine trial. Charlene McEvoy reports institutional support from AstraZeneca for a COVID-19 vaccine trial. Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy. Suchitra Rao reports grant funding from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Importance: Assessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance., Objective: To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta)., Design, Setting, and Participants: A test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states)., Exposures: Three doses of mRNA COVID-19 vaccine (third dose ≥14 days before test and ≥6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose)., Main Outcomes and Measures: Association between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status., Results: Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (Omicron N gene: 19.35 vs 18.52; Omicron ORF1ab gene: 19.25 vs 18.40; Delta N gene: 19.07 vs 17.52; Delta ORF1ab gene: 18.70 vs 17.28; Delta S gene: 23.62 vs 20.24)., Conclusions and Relevance: Among individuals seeking testing for COVID-like illness in the US in December 2021, receipt of 3 doses of mRNA COVID-19 vaccine (compared with unvaccinated and with receipt of 2 doses) was less likely among cases with symptomatic SARS-CoV-2 infection compared with test-negative controls. These findings suggest that receipt of 3 doses of mRNA vaccine, relative to being unvaccinated and to receipt of 2 doses, was associated with protection against both the Omicron and Delta variants, although the higher odds ratios for Omicron suggest less protection for Omicron than for Delta.

Estimates of COVID-19 mRNA vaccine effectiveness (VE) have declined in recent months (1,2) because of waning vaccine induced immunity over time,* possible increased immune evasion by SARS-CoV-2 variants (3), or a combination of these and other factors. CDC recommends that all persons aged ≥12 years receive a third dose (booster) of an mRNA vaccine ≥5 months after receipt of the second mRNA vaccine dose and that immunocompromised individuals receive a third primary dose. † A third dose of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine increases neutralizing antibody levels (4), and three recent studies from Israel have shown improved effectiveness of a third dose in preventing COVID-19 associated with infections with the SARS-CoV-2 B.1.617.2 (Delta) variant (5-7). Yet, data are limited on the real-world effectiveness of third doses of COVID-19 mRNA vaccine in the United States, especially since the SARS-CoV-2 B.1.1.529 (Omicron) variant became predominant in mid-December 2021. The VISION Network § examined VE by analyzing 222,772 encounters from 383 emergency departments (EDs) and urgent care (UC) clinics and 87,904 hospitalizations from 259 hospitals among adults aged ≥18 years across 10 states from August 26, 2021 ¶ to January 5, 2022. Analyses were stratified by the period before and after the Omicron variant became the predominant strain (>50% of sequenced viruses) at each study site. During the period of Delta predominance across study sites in the United States (August-mid-December 2021), VE against laboratory-confirmed COVID-19-associated ED and UC encounters was 86% 14-179 days after dose 2, 76% ≥180 days after dose 2, and 94% ≥14 days after dose 3. Estimates of VE for the same intervals after vaccination during Omicron variant predominance were 52%, 38%, and 82%, respectively. During the period of Delta variant predominance, VE against laboratory-confirmed COVID-19-associated hospitalizations was 90% 14-179 days after dose 2, 81% ≥180 days after dose 2, and 94% ≥14 days after dose 3. During Omicron variant predominance, VE estimates for the same intervals after vaccination were 81%, 57%, and 90%, respectively. The highest estimates of VE against COVID-19-associated ED and UC encounters or hospitalizations during both Delta- and Omicron-predominant periods were among adults who received a third dose of mRNA vaccine. All unvaccinated persons should get vaccinated as soon as possible. All adults who have received mRNA vaccines during their primary COVID-19 vaccination series should receive a third dose when eligible, and eligible persons should stay up to date with COVID-19 vaccinations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Stephanie A. Irving reports institutional support from Westat. Nicola P. Klein reports institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Scient (unrelated to the current work), and institutional support from Pfizer for COVID-19 vaccine clinical trials. Allison L. Naleway reports institutional support from Pfizer for a study of meningococcal B vaccine safety during pregnancy (unrelated to the current work). Charlene McEvoy reports institutional support from AztraZeneca for an AZD1222 COVID-19 vaccine trial. Suchitra Rao reports grant support from GlaxoSmithKline, Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Background: In the USA, COVID-19 vaccines became available in mid-December, 2020, with adults aged 65 years and older among the first groups prioritised for vaccination. We estimated the national-level impact of the initial phases of the US COVID-19 vaccination programme on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 65 years and older., Methods: We analysed population-based data reported to US federal agencies on COVID-19 cases, emergency department visits, hospital admissions, and deaths among adults aged 50 years and older during the period Nov 1, 2020, to April 10, 2021. We calculated the relative change in incidence among older age groups compared with a younger reference group for pre-vaccination and post-vaccination periods, defined by the week when vaccination coverage in a given age group first exceeded coverage in the reference age group by at least 1%; time lags for immune response and time to outcome were incorporated. We assessed whether the ratio of these relative changes differed when comparing the pre-vaccination and post-vaccination periods., Findings: The ratio of relative changes comparing the change in the COVID-19 case incidence ratio over the post-vaccine versus pre-vaccine periods showed relative decreases of 53% (95% CI 50 to 55) and 62% (59 to 64) among adults aged 65 to 74 years and 75 years and older, respectively, compared with those aged 50 to 64 years. We found similar results for emergency department visits with relative decreases of 61% (52 to 68) for adults aged 65 to 74 years and 77% (71 to 78) for those aged 75 years and older compared with adults aged 50 to 64 years. Hospital admissions declined by 39% (29 to 48) among those aged 60 to 69 years, 60% (54 to 66) among those aged 70 to 79 years, and 68% (62 to 73), among those aged 80 years and older, compared with adults aged 50 to 59 years. COVID-19 deaths also declined (by 41%, 95% CI -14 to 69 among adults aged 65-74 years and by 30%, -47 to 66 among those aged ≥75 years, compared with adults aged 50 to 64 years), but the magnitude of the impact of vaccination roll-out on deaths was unclear., Interpretation: The initial roll-out of the US COVID-19 vaccination programme was associated with reductions in COVID-19 cases, emergency department visits, and hospital admissions among older adults., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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: 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.)., (Copyright © 2021 Massachusetts Medical Society.)

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19. † ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vincent C. Marconi reports institutional support to Emory University from the AIDS Clinical Trials Group and the National Institutes of Health (NIH); grants from Lilly, Gilead, ViiV, NIH, and the Veterans Health Administration; payment or honoraria from Medscape, WebMD, ViiV, Integritas, and Lilly; travel support from NIH; and participation on an NIH Data Safety Monitoring Board. Miwako Kobayashi reports support for attending a meeting from the American Veterinary Medical Association. No other potential conflicts of interest were disclosed.

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., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Stephanie A. Irving reports support from Westat to Kaiser Permanente Northwest Center for Health Research. Nicola P. Klein reports support from Pfizer to Kaiser Permanente, Northern California for COVID-19 vaccine clinical trials, and institutional support from Merck, GlaxoSmithKline, and Sanofi Pasteur outside the current study. Charlene McEvoy reports support from AstraZeneca to HealthPartners Institute for COVID-19 vaccine trials. Allison L. Naleway reports Pfizer Research funding to Kaiser Permanente Northwest for unrelated study of meningococcal B vaccine safety during pregnancy. Suchitra Rao reports grants from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the U.S. adult population (1). Immunocompromised adults are at increased risk for severe COVID-19 outcomes (2) and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network* on hospitalizations among persons aged ≥18 years with COVID-19-like illness from 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses, † VE against COVID-19-associated hospitalization conferred by completing a 2-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date § (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of 2 doses of mRNA COVID-19 vaccine against COVID-19-associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%-80%) than among immunocompetent patients (90%; 95% CI = 89%-91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Allison L. Naleway reports institutional support from Pfizer outside the submitted work. Anupam B. Kharbanda reports institutional support through HealthPartners to Children’s Minnesota for VISION. Charlene McEvoy reports institutional support from AstraZeneca for the AZD1222 COVID-19 vaccine trial. Jill Ferdinands reports travel support from Institute for Influenza Epidemiology, funded in part by Sanofi Pasteur. Nicola P. Klein reports institutional support from Pfizer for COVID-19 vaccine clinical trials and institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) outside the submitted work. Suchitra Rao reports grant support from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

Objective: To determine the difference in rate of weight gain from birth to 5 years based on exposure to maternal group B streptococcal (GBS) intrapartum antibiotic prophylaxis (IAP)., Design: Retrospective cohort study of 13 804 infants., Setting: Two perinatal centres and a primary paediatric care network in Philadelphia., Participants: Term infants born 2007-2012, followed longitudinally from birth to 5 years of age., Exposures: GBS IAP defined as penicillin, ampicillin, cefazolin, clindamycin or vancomycin administered ≥4 hours prior to delivery to the mother. Reference infants were defined as born to mothers without (vaginal delivery) or with other (caesarean delivery) intrapartum antibiotic exposure., Outcomes: Difference in rate of weight change from birth to 5 years was assessed using longitudinal rate regression. Analysis was a priori stratified by delivery mode and adjusted for relevant covariates., Results: GBS IAP was administered to mothers of 2444/13 804 (17.7%) children. GBS IAP-exposed children had a significantly elevated rate of weight gain in the first 5 years among vaginally-born (adjusted rate difference 1.44% (95% CI 0.3% to 2.6%)) and caesarean-born (3.52% (95% CI 1.9% to 5.2%)) children. At 5 years, the rate differences equated to an additional 0.24 kg among vaginally-born children and 0.60 kg among caesarean-born children., Conclusion: GBS-specific IAP was associated with a modest increase in rate of early childhood weight gain. GBS IAP is an effective intervention to prevent perinatal GBS disease-associated morbidity and mortality. However, these findings highlight the need to better understand effects of intrapartum antibiotic exposure on childhood growth and support efforts to develop alternate prevention strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic., Methods: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation., Results: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit., Conclusions: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.)., (Copyright © 2021 Massachusetts Medical Society.)

Objective: To evaluate if facility-level vaccination after an initial vaccination clinic was independently associated with COVID-19 incidence adjusted for other factors in January 2021 among nursing home residents., Design: Ecological analysis of data from the CDC's National Healthcare Safety Network (NHSN) and from the CDC's Pharmacy Partnership for Long-Term Care Program., Setting and Participants: CMS-certified nursing homes participating in both NHSN and the Pharmacy Partnership for Long-Term Care Program., Methods: A multivariable, random intercepts, negative binomial model was applied to contrast COVID-19 incidence rates among residents living in facilities with an initial vaccination clinic during the week ending January 3, 2021 (n = 2843), vs those living in facilities with no vaccination clinic reported up to and including the week ending January 10, 2021 (n = 3216). Model covariates included bed size, resident SARS-CoV-2 testing, staff with COVID-19, cumulative COVID-19 among residents, residents admitted with COVID-19, community county incidence, and county social vulnerability index (SVI)., Results: In December 2020 and January 2021, incidence of COVID-19 among nursing home residents declined to the lowest point since reporting began in May, diverged from the pattern in community cases, and began dropping before vaccination occurred. Comparing week 3 following an initial vaccination clinic vs week 2, the adjusted reduction in COVID-19 rate in vaccinated facilities was 27% greater than the reduction in facilities where vaccination clinics had not yet occurred (95% confidence interval: 14%-38%, P < .05)., Conclusions and Implications: Vaccination of residents contributed to the decline in COVID-19 incidence in nursing homes; however, other factors also contributed. The decline in COVID-19 was evident prior to widespread vaccination, highlighting the benefit of a multifaced approach to prevention including continued use of recommended screening, testing, and infection prevention practices as well as vaccination to keep residents in nursing homes safe., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19-associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vincent C. Marconi reports research grants from Eli Lilly and Co., Gilead Sciences, and ViiV Healthcare. No other potential conflicts of interest were disclosed.

Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Samuel M. Brown reports personal fees from Hamilton, institutional fees from Faron Pharmaceuticals and Sedana, grants from Janssen, the National Institutes of Health (NIH), and the Department of Defense (DoD), book royalties from Oxford University and Brigham Young University, outside the submitted work. Jonathan D. Casey reports grants from NIH, outside the submitted work. Steven Y. Chang was a speaker for La Jolla Pharmaceuticals in 2018 and consulted for PureTech Health in 2020. James D. Chappell reports grants from NIH during the conduct of the study. Matthew C. Exline reports support from Abbott Labs for sponsored talks, outside the submitted work. D. Clark Files reports personal consultant fees from Cytovale and is a data and safety monitoring board (DSMB) member from Medpace, outside the submitted work. Adit A. Ginde reports grants from NIH, DoD, AbbVie, and Faron Pharmaceuticals, outside the submitted work. Michelle N. Gong reports grants from NIH and the Agency for Healthcare Research and Quality (AHRQ), DSMB membership fees from Regeneron, and personal fees from Philips Healthcare, outside the submitted work. Carlos G. Grijalva reports consultancy fees from Pfizer, Merck, and Sanofi-Pasteur; grants from Campbell Alliance/Syneos Health, NIH, the Food and Drug Administration, AHQR, and Sanofi, outside the submitted work. David N. Hager reports salary support from Incyte Corporation, the Marcus Foundation, and EMPACT Precision Medicine via Vanderbilt University Medical Center, outside the submitted work. Natasha Halasa reports grants and nonfinancial support from Sanofi, and Quidel outside the submitted work. Daniel J. Henning reports personal consultant fees from Cytovale and Opticyte. Akram Khan reports grants from United Therapeutics, Johnson & Johnson, 4D Medical, Lung LLC, and Reata Pharmaceuticals, outside the submitted work. Adam S. Lauring reports personal fees from Sanofi and Roche, outside the submitted work. Christopher J. Lindsell reports grants from NIH, DoD, and the Marcus Foundation; contract fees from bioMerieux, Endpoint LLC, and Entegrion Inc, outside the submitted work and has a patent for risk stratification in sepsis and septic shock issued. Emily T. Martin reports personal fees from Pfizer and grants from Merck, outside the submitted work. Arnold S. Monto reports consulting fees from Sanofi-Pasteur and Seqirus outside the submitted work. Ithan D. Peltan reports grants from NIH and Janssen Pharmaceuticals and institutional support from Asahi Kasei Pharma and Regeneron, outside the submitted work. Todd W. Rice reports personal fees from Cumberland Pharmaceuticals, Inc. and personal fees from Avisa Pharma, LLC and Sanofi, outside the submitted work. Wesley H. Self reports consulting fees from Aeprio Pharmaceuticals and Merck outside the submitted work. No other potential conflicts of interest were disclosed.

Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant † highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN) § were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated ¶ (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Intrapartum antibiotic prophylaxis (IAP) reduces a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI)., Methods: This was a retrospective cohort study of infants (n = 223 431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure., Results: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P < .0001 for all time points, ΔBMI at age 5 years 0.12 kg/m2, 95% confidence interval [CI]: .07-.16 kg/m2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P < .05 for 0.7-0.8 years, P < .0001 for all other time points) compared to other antibiotics (ΔBMI at age 5 years 0.24 kg/m2, 95% CI: .14-.34 kg/m2). Breastfeeding did not modify these associations., Conclusions: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Clinical trials of COVID-19 vaccines currently authorized for emergency use in the United States (Pfizer-BioNTech, Moderna, and Janssen [Johnson & Johnson]) indicate that these vaccines have high efficacy against symptomatic disease, including moderate to severe illness (1-3). In addition to clinical trials, real-world assessments of COVID-19 vaccine effectiveness are critical in guiding vaccine policy and building vaccine confidence, particularly among populations at higher risk for more severe illness from COVID-19, including older adults. To determine the real-world effectiveness of the three currently authorized COVID-19 vaccines among persons aged ≥65 years during February 1-April 30, 2021, data on 7,280 patients from the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) were analyzed with vaccination coverage data from state immunization information systems (IISs) for the COVID-NET catchment area (approximately 4.8 million persons). Among adults aged 65-74 years, effectiveness of full vaccination in preventing COVID-19-associated hospitalization was 96% (95% confidence interval [CI] = 94%-98%) for Pfizer-BioNTech, 96% (95% CI = 95%-98%) for Moderna, and 84% (95% CI = 64%-93%) for Janssen vaccine products. Effectiveness of full vaccination in preventing COVID-19-associated hospitalization among adults aged ≥75 years was 91% (95% CI = 87%-94%) for Pfizer-BioNTech, 96% (95% CI = 93%-98%) for Moderna, and 85% (95% CI = 72%-92%) for Janssen vaccine products. COVID-19 vaccines currently authorized in the United States are highly effective in preventing COVID-19-associated hospitalizations in older adults. In light of real-world data demonstrating high effectiveness of COVID-19 vaccines among older adults, efforts to increase vaccination coverage in this age group are critical to reducing the risk for COVID-19-related hospitalization., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Evan J. Anderson reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and GSK; personal fees from Sanofi-Pasteur, Pfizer, Medscape, Kentucky Bioprocessing, Inc, Janssen, outside the submitted work; and his institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Sue Kim reports grants from Michigan Department of Health and Human Services, during the conduct of the study. William Schaffner reports personal fees from VBI Vaccines, outside the submitted work. Jessica Shiltz reports grants from Council for State and Territorial Epidemiologists during the conduct of the study. No other potential conflicts of interest were disclosed.