Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization. In August 2023, a preventive monoclonal antibody (nirsevimab) was recommended for all infants aged <8 months (born during or entering their first RSV season) and for children aged 8-19 months (entering their second RSV season) who have increased risk for severe RSV illness, including all AI/AN children. This evaluation in Alaska's Yukon-Kuskokwim Delta region estimated nirsevimab effectiveness among AI/AN children in their first or second RSV seasons during 2023-2024. Among 472 children with medically attended acute respiratory illness (ARI), 48% overall had received nirsevimab ≥7 days earlier (median = 91 days before the ARI-related visit). For children in their first RSV season (292), nirsevimab effectiveness was 76% (95% CI = 42%-90%) against medically attended RSV illness and 89% (95% CI = 32%-98%) against RSV hospitalization. For children in their second RSV season (180), effectiveness against medically attended RSV illness was 88% (95% CI = 48%-97%). Nirsevimab is effective for preventing severe RSV illness among infants entering their first RSV season and children entering their second season with increased risk for severe RSV, including all AI/AN children.

Test-negative designs (TNDs) are used to assess vaccine effectiveness (VE). Protection from infection-induced immunity may confound the association between case and vaccination status, but collecting reliable infection history can be challenging. If vaccinated individuals have less infection-induced protection than unvaccinated individuals, failure to account for infection history could underestimate VE, though the bias is not well understood. We simulated individual-level SARS-CoV-2 infection and COVID-19 vaccination histories and a TND. VE against symptomatic infection and VE against severe disease estimates unadjusted for infection history underestimated VE compared to estimates adjusted for infection history, and unadjusted estimates were more likely to be below 0%, which could lead to an incorrect interpretation that COVID-19 vaccines are harmful. TNDs assessing VE immediately following vaccine rollout introduced the largest bias and potential for negative VE against symptomatic infection. Despite the potential for bias, VE estimates from TNDs without prior infection information are useful because underestimation is rarely more than 8 percentage points.

BACKGROUND: On September 2, 2022, bivalent COVID-19 mRNA vaccines, were recommended to address reduced effectiveness of COVID-19 monovalent vaccines during SARS-CoV-2 Omicron variant predominance. METHODS: Using national pharmacy-based SARS-CoV-2 testing program data from January 15 to September 11, 2023, this test-negative, case-control design study assessed bivalent COVID-19 vaccine effectiveness (VE) against symptomatic infection. RESULTS: VE against symptomatic infection of a bivalent dose between 2 weeks and 1 month after bivalent vaccination ranged from 46% (95% CI: 38%-52%) for those aged ≥ 65 years to 61% (95% CI 41%-75%) for those aged 12-17 years. CONCLUSION: Bivalent vaccines protected against symptomatic infection. However, effectiveness waned over time, emphasizing the need to stay up to date with COVID-19 vaccination.

BACKGROUND: Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. METHODS: We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. FINDINGS: Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. INTERPRETATION: Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. FUNDING: The Centers for Disease Control and Prevention.

The SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, this surge in infections was not accompanied by COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86 lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86 lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86 lineages experienced greater numbers of documented prior SARS-CoV-2 infections. Cases infected with BA.2.86 lineages also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.

COVID-19 vaccination provides additional protection against severe COVID-19-associated illness and death. Since September 2023, 2023-2024 Formula monovalent XBB.1-strain COVID-19 vaccines have been recommended for use in the United States for all persons aged ≥6 months. However, SARS-CoV-2 continues to evolve, and since winter 2023-2024, Omicron JN.1 lineage strains of SARS-CoV-2, including the JN.1 strain and the KP.2 strain, have been widely circulating in the United States. Further, COVID-19 vaccine effectiveness is known to wane. On June 27, 2024, the Advisory Committee on Immunization Practices (ACIP) recommended 2024-2025 COVID-19 vaccination with a Food and Drug Administration (FDA)-approved or authorized vaccine for all persons aged ≥6 months. On August 22, 2024, FDA approved the 2024-2025 COVID-19 vaccines by Moderna and Pfizer-BioNTech (based on the KP.2 strain) for use in persons aged ≥12 years and authorized these vaccines for use in children aged 6 months-11 years under Emergency Use Authorization (EUA). On August 30, 2024, FDA authorized 2024-2025 COVID-19 vaccine by Novavax (based on the JN.1 strain) for use in persons aged ≥12 years under EUA. ACIP will continue to evaluate new evidence as it becomes available and will update recommendations as needed.

Pregnant people face increased risk of severe COVID-19. Current guidelines recommend updated COVID-19 vaccination (2023-2024) for those aged ≥6 months, irrespective of pregnancy status. To refine recommendations for pregnant people, further data are needed. Using a test-negative design, we evaluated COVID-19 vaccine effectiveness against medically attended COVID-19 with COVID-19-like illness among pregnant people aged 18 to 45 years during June 2022 to August 2023. When doses were received during pregnancy, vaccine effectiveness was 52% (95% CI, 29%-67%); when received <6 months prior to pregnancy, 28% (95% CI, 11%-42%); and when received ≥6 months prior to pregnancy, 6% (95% CI, -11% to 21%). Pregnant people should stay up-to-date with recommended COVID-19 vaccination.

BACKGROUND: Residents of nursing homes remain an epidemiologically important population for COVID-19 prevention efforts, including vaccination. We aim to understand effectiveness of bivalent vaccination for preventing SARS-CoV-2 infections in this population. METHODS: We used a retrospective cohort of nursing home residents from November 1, 2022, through March 31, 2023, to identify new SARS-CoV-2 infections. A Cox proportional hazards model was used to estimate hazard ratios comparing residents with a bivalent vaccination compared with residents not up to date with vaccination recommendations. Vaccine effectiveness was estimated as (1 - Hazard Ratio) * 100. RESULTS: Among 6,916 residents residing in 76 nursing homes included in our cohort, 3,211 (46%) received a bivalent vaccine 7 or more days prior to censoring. Adjusted vaccine effectiveness against laboratory confirmed SARS-CoV-2 infection comparing receipt of a bivalent vaccine versus not up to date vaccine status was 29% (95% Confidence interval 18% to 39%). Vaccine effectiveness for receipt of a bivalent vaccine against residents who were unvaccinated or vaccinated more than a year prior was 32% (95% CI: 20% to 42%,) and was 25% compared with residents who were vaccinated with a monovalent vaccine in the past 61-365 days (95% CI:10% to 37%). CONCLUSIONS: Bivalent COVID-19 vaccines provided additional protection against SARS-CoV-2 infections in nursing home residents during our study time-period, compared to both no vaccination or vaccination more than a year ago and monovalent vaccination 60 - 365 days prior. Ensuring nursing home residents stay up to date with vaccine recommendations remains a critical tool for COVID-19 prevention efforts.

COVID-19 remains an important public health threat, despite overall decreases in COVID-19-related severe disease since the start of the COVID-19 pandemic. COVID-19-associated hospitalization rates remain higher among adults aged ≥65 years relative to rates in younger adults, adolescents, and children; during October 2023-January 2024, 67% of all COVID-19-associated hospitalizations were among persons aged ≥65 years. On September 12, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommended updated (2023-2024 Formula) COVID-19 vaccination with a monovalent XBB.1.5-derived vaccine for all persons aged ≥6 months to protect against severe COVID-19-associated illness and death. Because SARS-CoV-2 continues to circulate throughout the year, and because of the increased risk for COVID-19-related severe illness in persons aged ≥65 years, the protection afforded by updated vaccines against JN.1 and other currently circulating variants, and the expected waning of vaccine-conferred protection against disease, on February 28, 2024, ACIP recommended all persons aged ≥65 years receive 1 additional dose of the updated (2023-2024 Formula) COVID-19 vaccine. Implementation of these recommendations is expected to enhance immunity that might have waned and decrease the risk for severe COVID-19-associated outcomes, including death, among persons aged ≥65 years.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. As with past COVID-19 vaccines, additional doses may be considered for persons with immunocompromising conditions, who are at higher risk for severe COVID-19 and might have decreased response to vaccination. In this analysis, vaccine effectiveness (VE) of an updated COVID-19 vaccine dose against COVID-19-associated hospitalization was evaluated during September 2023-February 2024 using data from the VISION VE network. Among adults aged ≥18 years with immunocompromising conditions, VE against COVID-19-associated hospitalization was 38% in the 7-59 days after receipt of an updated vaccine dose and 34% in the 60-119 days after receipt of an updated dose. Few persons (18%) in this high-risk study population had received updated COVID-19 vaccine. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccination; persons with immunocompromising conditions may get additional updated COVID-19 vaccine doses ≥2 months after the last recommended COVID-19 vaccine.

BACKGROUND: Although psychiatric disorders have been associated with reduced immune responses to other vaccines, it remains unknown whether they influence COVID-19 vaccine effectiveness (VE). This study evaluated risk of COVID-19 hospitalization and estimated mRNA VE stratified by psychiatric disorder status. METHODS: In a retrospective cohort analysis of the VISION Network in four US states, the rate of laboratory-confirmed COVID-19-associated hospitalization between December 2021 and August 2022 was compared across psychiatric diagnoses and by monovalent mRNA COVID-19 vaccination status using Cox proportional hazards regression. RESULTS: Among 2,436,999 adults, 22.1% had ≥1 psychiatric disorder. The incidence of COVID-19-associated hospitalization was higher among patients with any versus no psychiatric disorder (394 vs. 156 per 100,000 person-years, p < 0.001). Any psychiatric disorder (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.18-1.37) and mood (aHR, 1.25; 95% CI, 1.15-1.36), anxiety (aHR, 1.33, 95% CI, 1.22-1.45), and psychotic (aHR, 1.41; 95% CI, 1.14-1.74) disorders were each significant independent predictors of hospitalization. Among patients with any psychiatric disorder, aHRs for the association between vaccination and hospitalization were 0.35 (95% CI, 0.25-0.49) after a recent second dose, 0.08 (95% CI, 0.06-0.11) after a recent third dose, and 0.33 (95% CI, 0.17-0.66) after a recent fourth dose, compared to unvaccinated patients. Corresponding VE estimates were 65%, 92%, and 67%, respectively, and were similar among patients with no psychiatric disorder (68%, 92%, and 79%). CONCLUSION: Psychiatric disorders were associated with increased risk of COVID-19-associated hospitalization. However, mRNA vaccination provided similar protection regardless of psychiatric disorder status, highlighting its benefit for individuals with psychiatric disorders.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally.

On September 12, 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (updated) COVID-19 vaccination with a monovalent XBB.1.5-derived vaccine for all persons aged ≥6 months to prevent COVID-19, including severe disease. During fall 2023, XBB lineages co-circulated with JN.1, an Omicron BA.2.86 lineage that emerged in September 2023. These variants have amino acid substitutions that might increase escape from neutralizing antibodies. XBB lineages predominated through December 2023, when JN.1 became predominant in the United States. Reduction or failure of spike gene (S-gene) amplification (i.e., S-gene target failure [SGTF]) in real-time reverse transcription-polymerase chain reaction testing is a time-dependent, proxy indicator of JN.1 infection. Data from the Increasing Community Access to Testing SARS-CoV-2 pharmacy testing program were analyzed to estimate updated COVID-19 vaccine effectiveness (VE) (i.e., receipt versus no receipt of updated vaccination) against symptomatic SARS-CoV-2 infection, including by SGTF result. Among 9,222 total eligible tests, overall VE among adults aged ≥18 years was 54% (95% CI = 46%-60%) at a median of 52 days after vaccination. Among 2,199 tests performed at a laboratory with SGTF testing, VE 60-119 days after vaccination was 49% (95% CI = 19%-68%) among tests exhibiting SGTF and 60% (95% CI = 35%-75%) among tests without SGTF. Updated COVID-19 vaccines provide protection against symptomatic infection, including against currently circulating lineages. CDC will continue monitoring VE, including for expected waning and against severe disease. All persons aged ≥6 months should receive an updated COVID-19 vaccine dose.

To support efforts to vaccinate millions of Americans across the United States (US) against COVID-19, the US federal government (USG) launched the Pharmacy Partnership for Long-Term Care Program (PPP) in December 2020 and the Federal Retail Pharmacy Program (FRPP) in February 2021. These programs consisted of a collaborative partnership with the USG and 21 pharmacy organizations, including large retail chains, coordinating pharmacy services administrative organizations (PSAOs) representing independent retail and long-term care pharmacies, and pharmacy network administrators. These pharmacy organizations represented over 46,000 providers and created a robust channel for far-reaching COVID-19 vaccination across 56 state and local jurisdictions. PPP reported more than 8 million COVID-19 doses administered to residents and staff in long-term care facilities (LTCFs) as of June 2021. In addition, FRPP was responsible for administering more than 304 million doses, accounting for approximately 49% of all COVID-19 doses administered as of June 2023. This unprecedented public-private partnership allowed USG to rapidly adapt, expand, and aim to provide equitable access to vaccines for adults and eligible-aged children during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, the FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. End-to-end informatics support helped pharmacies meet critical national public health goals and served as convenient access points for sustained health services. This manuscript describes lessons learned regarding informatics coordination with participating pharmacy partners to support the rapid and safe administration of COVID-19 vaccines across the US. The processes of onboarding to CDC's complex data network, establishing connections to state and local immunization information systems (IIS), and monitoring the quality of data pharmacy partners submitted to the CDC Data Clearinghouse (DCH) in alignment with the COVID-19 Vaccine Reporting Specifications (CVRS) are highlighted.

COVID-19 has been associated with an increased risk for thromboembolic events, including ischemic stroke, venous thromboembolism, and myocardial infarction. Studies have reported lower rates of COVID-19-related thromboembolic events among persons who received the COVID-19 vaccine compared with persons who did not, but rigorous estimates of vaccine effectiveness (VE) in preventing COVID-19-related thromboembolic events are lacking. This analysis estimated the incremental benefit of receipt of a bivalent mRNA COVID-19 vaccine after receiving an original monovalent COVID-19 vaccine. To estimate VE of a bivalent mRNA COVID-19 dose in preventing thromboembolic events compared with original monovalent COVID-19 vaccine doses only, two retrospective cohort studies were conducted among Medicare fee-for-service enrollees during September 4, 2022-March 4, 2023. Effectiveness of a bivalent COVID-19 vaccine dose against COVID-19-related thromboembolic events compared with that of original vaccine alone was 47% (95% CI = 45%-49%) among Medicare enrollees aged ≥65 years and 51% (95% CI = 39%-60%) among adults aged ≥18 years with end stage renal disease receiving dialysis. VE was similar among Medicare beneficiaries with immunocompromise: 46% (95% CI = 42%-49%) among adults aged ≥65 years and 45% (95% CI = 24%-60%) among those aged ≥18 years with end stage renal disease. To help prevent complications of COVID-19, including thromboembolic events, adults should stay up to date with COVID-19 vaccination.

From December 2020 through March 2023, the COVID-19 vaccination efforts in long-term care (LTC) settings, identified many gaps and opportunities to improve public health capacity to support vaccine distribution, education, and documentation of COVID-19 vaccines administered to LTC residents and staff. Partner engagement at the local, state, and federal levels helped establish pathways for dissemination of information, improve access and delivery of vaccines, and expand reporting of vaccine administration data to monitor the impact of COVID-19 vaccination in LTC settings. Sustaining the improvements to the vaccine infrastructure in LTC settings that were created or enhanced during the COVID-19 vaccination efforts is critical for the protection of residents and staff against COVID-19 and other vaccine preventable respiratory outbreaks in the future.

COVID-19 vaccines represent a great scientific and public health achievement in the face of overwhelming pressures from a global pandemic, preventing millions of hospitalizations and deaths due to COVID-19 vaccines in the United States. Over 675 million doses of COVID-19 vaccines have been administered in the United States, and over 80% of the U.S. population has had at least 1 dose of a COVID-19 vaccine. Over the course of the COVID-19 pandemic in the United States, over one million people died from COVID-19, and over six million were hospitalized. It has been estimated that COVID-19 vaccines prevented more than 18 million additional hospitalizations and more than 3 million additional deaths due to COVID-19 in the United States. From the beginning of the COVID-19 pandemic in 2020 through June 2023, ACIP had 35 COVID-19 focused meetings and 24 votes for COVID-19 vaccine recommendations. ACIP had the critical task of rapidly and thoroughly reviewing emerging and evolving data on COVID-19 epidemiology and vaccines, as well as making comprehensive population-based recommendations for vaccine policy and considerations for implementation through a transparent and evidence-based framework. Safe and effective COVID-19 vaccines, recommended through transparent policy discussions with ACIP, remain the best tool we have to prevent serious illness, hospitalization and death from COVID-19.

COVID-19 vaccines were originally authorized in the United States in December 2020 on the basis of safety, immunogenicity, and clinical efficacy data from randomized controlled trials (RCTs). However, real-world vaccine effectiveness (VE) data are necessary to provide information on how the vaccines work in populations not included in the RCTs (e.g., nursing home residents), against new SARS-CoV-2 variants, with increasing time since vaccination, and in populations with increasing levels of prior infection. The goal of CDC's COVID-19 VE program is to provide timely and robust data to support ongoing policy decisions and implementation of vaccination and includes VE platforms to study the spectrum of illness, from infection to critical illness. Challenges to estimating VE include accurate ascertainment of vaccination history, outcome status, changing rates of prior infection, emergence of new variants, and appropriate interpretation of absolute and relative VE measures. CDC COVID-19 VE platforms have played a pivotal role in numerous vaccine policy decisions since 2021 and will continue to play a key role in future decisions as the vaccine program moves from an emergency response to a routine schedule.

Test-negative-design COVID-19 vaccine effectiveness (VE) studies use symptomatic SARS-CoV-2-positive individuals as cases and symptomatic SARS-CoV-2-negative individuals as controls to evaluate COVID-19 VE. To evaluate the potential bias introduced by the correlation of COVID-19 and influenza vaccination behaviors, we assessed changes in estimates of VE of bivalent vaccines against COVID-19-associated hospitalizations and emergency department/urgent care (ED/UC) encounters when considering influenza vaccination status or including or excluding influenza-positive controls using data from the multi-state VISION vaccine effectiveness network. Analyses included encounters during October 2022 - February 2023, a period of SARS-CoV-2 and influenza cocirculation. When considering influenza vaccination status or including or excluding influenza-positive controls, COVID-19 VE estimates were robust, with most VE estimates against COVID-19-associated hospitalization and ED/UC encounters changing less than 5 percentage points. Higher proportions of influenza-positive patients among controls, influenza vaccination coverage, or VE could impact these findings; the potential bias should continue to be assessed.

Adults with disabilities are at increased risk for severe coronavirus disease 2019 (COVID-19). Using data across 9 states during Delta- and Omicron-predominant periods (June 2021-September 2022), we evaluated the effectiveness of the original monovalent COVID-19 messenger RNA vaccines among 521 206 emergency department/urgent care encounters (11 471 [2%] in patients with a documented disability) and 139 548 hospitalizations (16 569 [12%] in patients with a disability) for laboratory-confirmed COVID-19 illness in adults (aged ≥18 years). Across variant periods and for the primary series or booster doses, vaccine effectiveness was similar in those with and those without a disability. These findings highlight the importance of adults with disabilities staying up to date with COVID-19 vaccinations.

COVID-19 vaccines protect against severe COVID-19-associated outcomes, including hospitalization and death. As SARS-CoV-2 has evolved, and waning vaccine effectiveness has been noted, vaccine formulations and policies have been updated to provide continued protection against severe illness and death from COVID-19. Since September 2022, bivalent mRNA COVID-19 vaccines have been recommended in the United States, but the variants these vaccines protect against are no longer circulating widely. On September 11, 2023, the Food and Drug Administration (FDA) approved the updated (2023-2024 Formula) COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech for persons aged ≥12 years and authorized these vaccines for persons aged 6 months-11 years under Emergency Use Authorization (EUA). On October 3, 2023, FDA authorized the updated COVID-19 vaccine by Novavax for use in persons aged ≥12 years under EUA. The updated COVID-19 vaccines include a monovalent XBB.1.5 component, which is meant to broaden vaccine-induced immunity and provide protection against currently circulating SARS-CoV-2 XBB-sublineage variants including against severe COVID-19-associated illness and death. On September 12, 2023, the Advisory Committee on Immunization Practices recommended vaccination with updated COVID-19 vaccines for all persons aged ≥6 months. These recommendations will be reviewed as new evidence becomes available or new vaccines are approved and might be updated.

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.

BACKGROUND: The epidemiology of COVID-19 continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of hospitalized COVID-19 and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023 when multiple SARS-CoV-2 variants or sub-lineages predominated. We evaluated changes in baseline demographic and clinical characteristics and critical outcomes (intensive care unit admission and/or death) and used regression models to evaluate critical outcomes risk factors (risk ratios) stratified by COVID-19 vaccination status. RESULTS: 60,488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, from Delta period (June-December 2021) to the Omicron post-BA.4/BA.5 period (September 2022-March 2023), median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, while critical outcomes declined from 24.8% to 19.4% (all p < 0.001). Compared to all hospitalization events, those with critical outcomes had a higher proportion of four or more categories of medical conditions categories assessed (32.8% critical versus 23.0% all hospitalized). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated aRR 2.27 [95% CI: 2.14-2.41]; vaccinated aRR 1.73 [95% CI: 1.56-1.92]) across periods. CONCLUSION: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time and median patient age increased with time. Multimorbidity was mostly strongly associated with critical outcomes.

On June 19, 2022, the original monovalent mRNA COVID-19 vaccines were approved as a primary series for children aged 6 months-4 years (Pfizer-BioNTech) and 6 months-5 years (Moderna) based on safety, immunobridging, and limited efficacy data from clinical trials. On December 9, 2022, CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months. mRNA COVID-19 vaccine effectiveness (VE) against emergency department or urgent care (ED/UC) encounters was evaluated within the VISION Network during July 4, 2022-June 17, 2023, among children with COVID-19-like illness aged 6 months-5 years. Among children aged 6 months-5 years who received molecular SARS-CoV-2 testing during August 1, 2022-June 17, 2023, VE of 2 monovalent Moderna doses against ED/UC encounters was 29% (95% CI = 12%-42%) ≥14 days after dose 2 (median = 100 days after dose 2; IQR = 63-155 days). Among children aged 6 months-4 years with a COVID-19-like illness who received molecular testing during September 19, 2022-June 17, 2023, VE of 3 monovalent Pfizer-BioNTech doses was 43% (95% CI = 17%-61%) ≥14 days after dose 3 (median = 75 days after dose 3; IQR = 40-139 days). Effectiveness of ≥1 bivalent dose, comparing children with at least a complete primary series and ≥1 bivalent dose to unvaccinated children, irrespective of vaccine manufacturer, was 80% (95% CI = 42%-96%) among children aged 6 months-5 years a median of 58 days (IQR = 32-83 days) after the dose. All children should stay up to date with recommended COVID-19 vaccines, including initiation of COVID-19 vaccination immediately when they are eligible.

To help achieve the initial goal of providing universal COVID-19 vaccine access to approximately 258 million adults in 62 US jurisdictions, the federal government launched the Federal Retail Pharmacy Program (FRPP) on February 11, 2021. We describe FRPP's collaboration among the federal government, US jurisdictions, federal entity partners, and 21 national chain and independent pharmacy networks to provide large-scale access to COVID-19 vaccines, particularly in communities disproportionately affected by COVID-19 (eg, people aged ≥65 years, people from racial and ethnic minority groups). FRPP initially provided 10 000 vaccination sites for people to access COVID-19 vaccines, which was increased to >35 000 vaccination sites by May 2021 and sustained through January 31, 2022. From February 11, 2021, through January 31, 2022, FRPP vaccination sites received 293 million doses and administered 219 million doses, representing 45% of all COVID-19 immunizations provided nationwide (38% of all first doses, 72% of all booster doses). This unprecedented public-private partnership allowed the federal government to rapidly adapt and scale up an equitable vaccination program to reach adults, later expanding access to vaccine-eligible children, during the COVID-19 pandemic. As the largest federal COVID-19 vaccination program, FRPP exemplifies how public-private partnerships can expand access to immunizations during a public health emergency. Pharmacies can help meet critical national public health goals by serving as convenient access points for sustained health services. Lessons learned from this effort-including the importance of strong coordination and communication, efficient reporting systems and data quality, and increasing access to and demand for vaccine, among others-may help improve future immunization programs and support health system resiliency, emphasizing community-level access and health equity during public health emergencies.

Monitoring COVID-19 vaccination coverage among nursing home (NH) residents and staff is important to ensure high coverage and guide patient-safety policies. With the termination of the federal Pharmacy Partnership for Long-Term Care Program, another source of facility-based vaccination data is needed. We compared numbers of COVID-19 vaccinations administered to NH residents and staff reported by pharmacies participating in the temporary federal Pharmacy Partnership for Long-Term Care Program with those reported by NHs participating in new COVID-19 vaccination modules of CDC’s National Healthcare Safety Network (NHSN). Pearson correlation coefficients comparing the number vaccinated between the two approaches were 0.89, 0.96, and 0.97 for residents and 0.74, 0.90, and 0.90 for staff, in the weeks ending January 3, 10, and 17, respectively. Based on subsequent NHSN reporting, vaccination coverage with ≥1 vaccine dose reached 77% for residents and 50% for staff the week ending January 31 and plateaued through April 2021.Three-question summary boxWhat is the current understanding of the subject?Because of high risk of disease, nursing home residents and staff were prioritized for COVID-19 vaccination when doses were limited.What does this report add to the literature?National monitoring of nursing home residents and staff vaccination coverage through the CDC National Healthcare Safety Network (NHSN) correlated with vaccination administration reports from the federal Pharmacy Partnership for Long-Term Care Program in January 2021. NHSN-reported vaccination coverage rates plateaued from February through April 2021.What are the implications for public health practice?NHSN can track COVID-19 vaccination in nursing homes and help guide efforts to increase vaccine uptake in residents and staff.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors received no financial support for the research, authorship, and/or publication of this article.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy (See e.g., 45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. section 241(d); 5 U.S.C. section 552a; 44 U.S.C. section 3501 et seq.).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData supporting the findings of the study are found in the manuscript and/or supplementary files. Any other data can be furnished upon request.

Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission.Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention.Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had ≥1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had ≥1 respiratory sample tested, was 13% (95% CI: 4 – 38%).Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was sought or received.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be available upon reasonable request.

Background: In the United States, national ecological studies suggest a positive impact of COVID-19 vaccination coverage on outcomes in adults. However, the national impact of the vaccination program on COVID-19 in children remains unknown. To determine the association of COVID-19 vaccination with U.S. case incidence, emergency department visits, and hospital admissions for pediatric populations during the Delta and Omicron periods. Method(s): We conducted an ecological analysis among children aged 5-17 and compared incidence rate ratios (RRs) of COVID-19 cases, emergency department visits, and hospital admissions by pediatric vaccine coverage, with jurisdictions in the highest vaccine coverage quartile as the reference. Result(s): RRs comparing states with lowest pediatric vaccination coverage to the highest pediatric vaccination coverage were 2.00 and 0.64 for cases, 2.96 and 1.11 for emergency department visits, and 2.76 and 1.01 for hospital admissions among all children during the Delta and Omicron periods, respectively. During the 3-week peak period of the Omicron wave, only children aged 12-15 and 16-17 years in the states with the lowest versus highest coverage, had a significantly higher rate of emergency department visits (RR=1.39 and RR=1.34, respectively). Conclusion(s): COVID-19 vaccines were associated with lower case incidence, emergency department visits and hospital admissions among children during the Delta period but the association was weaker during the Omicron period. Pediatric COVID-19 vaccination should be promoted as part of a program to decrease COVID-19 impact among children; however, vaccine effectiveness may be limited when available vaccines do not match circulating viral variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: Understanding the usefulness of additional COVID-19 vaccine doses-particularly given varying disease incidence-is needed to support public health policy. We characterize the benefits of COVID-19 booster doses using number needed to vaccinate (NNV) to prevent one COVID-19-associated hospitalization or emergency department encounter. METHODS: We conducted a retrospective cohort study of immunocompetent adults at five health systems in four U.S. states during SARS-CoV-2 Omicron BA.1 predominance (December 2021-February 2022). Included patients completed a primary mRNA COVID-19 vaccine series and were either eligible to or received a booster dose. NNV were estimated using hazard ratios for each outcome (hospitalization and emergency department encounters), with results stratified by three 25-day periods and site. FINDINGS: 1,285,032 patients contributed 938 hospitalizations and 2076 emergency department encounters. 555,729 (43.2%) patients were aged 18-49 years, 363,299 (28.3%) 50-64 years, and 366,004 (28.5%) ≥65 years. Most patients were female (n = 765,728, 59.6%), White (n = 990,224, 77.1%), and non-Hispanic (n = 1,063,964, 82.8%). 37.2% of patients received a booster and 62.8% received only two doses. Median estimated NNV to prevent one hospitalization was 205 (range 44-615) and NNV was lower across study periods for adults aged ≥65 years (110, 46, and 88, respectively) and those with underlying medical conditions (163, 69, and 131, respectively). Median estimated NNV to prevent one emergency department encounter was 156 (range 75-592). INTERPRETATION: The number of patients needed to receive a booster dose was highly dependent on local disease incidence, outcome severity, and patient risk factors for moderate-to-severe disease. FUNDING: Funding was provided by the Centers for Disease Control and Prevention though contract 75D30120C07986 to Westat, Inc. and contract 75D30120C07765 to Kaiser Foundation Hospitals.