Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Hospitalization Among Adults Aged ≥18 Years with Immunocompromising Conditions - VISION Network, September 2023-February 2024.

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.

Risk of COVID-19 Hospitalization and Protection Associated With mRNA Vaccination Among US Adults With Psychiatric Disorders.

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.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

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.

Clinical Epidemiology and Risk Factors for Critical Outcomes Among Vaccinated and Unvaccinated Adults Hospitalized With COVID-19-VISION Network, 10 States, June 2021-March 2023.

BACKGROUND: The epidemiology of coronavirus disease 2019 (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 COVID-19 hospitalizations 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. We evaluated changes in demographics, clinical characteristics, and critical outcomes (intensive care unit admission and/or death) and evaluated critical outcomes risk factors (risk ratios [RRs]), stratified by COVID-19 vaccination status. RESULTS: A total of 60 488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, and critical outcomes declined from 24.8% to 19.4% (all P < .001) between the Delta (June-December, 2021) and post-BA.4/BA.5 (September 2022-March 2023) periods. Hospitalization events with critical outcomes had a higher proportion of ≥4 categories of medical condition categories assessed (32.8%) compared to all hospitalizations (23.0%). 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: adjusted RR, 2.27 [95% confidence interval {CI}, 2.14-2.41]; vaccinated: adjusted RR, 1.73 [95% CI, 1.56-1.92]) across periods. CONCLUSIONS: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time, and median patient age increased with time. Multimorbidity was most strongly associated with critical outcomes.

Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023.

BACKGROUND: The 2022-2023 United States influenza season had unusually early influenza activity with high hospitalization rates. Vaccine-matched A(H3N2) viruses predominated, with lower levels of A(H1N1)pdm09 activity also observed. METHODS: Using the test-negative design, we evaluated influenza vaccine effectiveness (VE) during the 2022-2023 season against influenza-A-associated emergency department/urgent care (ED/UC) visits and hospitalizations from October 2022-March 2023 among adults (age ≥18 years) with acute respiratory illness (ARI). VE was estimated by comparing odds of seasonal influenza vaccination among case-patients (influenza A test-positive by molecular assay) and controls (influenza test-negative), applying inverse-propensity-to-be-vaccinated weights. RESULTS: The analysis included 85,389 ED/UC ARI encounters (17.0% influenza-A-positive; 37.8% vaccinated overall) and 19,751 hospitalizations (9.5% influenza-A-positive; 52.8% vaccinated overall). VE against influenza-A-associated ED/UC encounters was 44% (95% confidence interval [95%CI]: 40-47%) overall and 45% and 41% among adults aged 18-64 and ≥65 years, respectively. VE against influenza-A-associated hospitalizations was 35% (95%CI: 27-43%) overall and 23% and 41% among adults aged 18-64 and ≥65 years, respectively. CONCLUSIONS: VE was moderate during the 2022-2023 influenza season, a season characterized with increased burden of influenza and co-circulation with other respiratory viruses. Vaccination is likely to substantially reduce morbidity, mortality, and strain on healthcare resources.

Effectiveness of the Original Monovalent Coronavirus Disease 2019 Vaccines in Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Adults With Disabilities: VISION Network, June 2021-September 2022.

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.

Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season, VISION Network.

BACKGROUND: During the 2022-2023 influenza season, the United States experienced the highest influenza-associated pediatric hospitalization rate since 2010-2011. Influenza A/H3N2 infections were predominant. METHODS: We analyzed acute respiratory illness (ARI)-associated emergency department or urgent care (ED/UC) encounters or hospitalizations at three health systems among children and adolescents aged 6 months-17 years who had influenza molecular testing during October 2022-March 2023. We estimated influenza A vaccine effectiveness (VE) using a test-negative approach. The odds of vaccination among influenza-A-positive cases and influenza-negative controls were compared after adjusting for confounders and applying inverse-propensity-to-be-vaccinated weights. We developed overall and age-stratified VE models. RESULTS: Overall, 13,547 of 44,787 (30.2%) eligible ED/UC encounters and 263 of 1,862 (14.1%) hospitalizations were influenza-A-positive cases. Among ED/UC patients, 15.2% of influenza-positive versus 27.1% of influenza-negative patients were vaccinated; VE was 48% (95% confidence interval [CI], 44%-52%) overall, 53% (95% CI, 47%-58%) among children aged 6 months-4 years and 38% (95% CI, 30%-45%) among those aged 9-17 years. Among hospitalizations, 17.5% of influenza-positive versus 33.4% of influenza-negative patients were vaccinated; VE was 40% (95% CI, 6%-61%) overall, 56% (95% CI, 23%-75%) among children ages 6 months-4 years and 46% (95% CI, 2%-70%) among those 5-17 years. CONCLUSIONS: During the 2022-2023 influenza season, vaccination reduced the risk of influenza-associated ED/UC encounters and hospitalizations by almost half (overall VE 40-48%). Influenza vaccination is a critical tool to prevent moderate-to-severe influenza illness in children and adolescents.

Impact of accounting for correlation between COVID-19 and influenza vaccination in a COVID-19 vaccine effectiveness evaluation using a test-negative design.

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.

Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing COVID-19-Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months-5 Years - VISION Network, United States, July 2022-June 2023.

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.

Effectiveness of COVID-19 vaccines at preventing emergency department or urgent care encounters and hospitalizations among immunocompromised adults: An observational study of real-world data across 10 US states from August-December 2021.

BACKGROUND: Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. METHODS: Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. RESULTS: We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. CONCLUSIONS: During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.

Engaging Patients and Other Stakeholders in "Designing for Dissemination" of Record Linkage Methods and Tools.

BACKGROUND: Novel record linkage (RL) methods have the potential to enhance clinical informatics by integrating patient data from multiple sources-including electronic health records, insurance claims, and digital health devices-to inform patient-centered care. Engaging patients and other stakeholders in the use of RL methods in patient-centered outcomes research (PCOR) is a key step in ensuring RL methods are viewed as acceptable, appropriate, and useful. The University of Colorado Record Linkage (CURL) platform empowers the use of RL in PCOR. OBJECTIVES: This study aimed to describe the process of engaging patients and other stakeholders in the design of an RL dissemination package to support the use of RL methods in PCOR. METHODS: Customer discovery, value proposition design, and user experience methods were used to iteratively develop an RL dissemination package that includes animated explainer videos for patients and an RL research planning workbook for researchers. Patients and other stakeholders (researchers, data managers, and regulatory officials) were engaged in the RL dissemination package design. RESULTS: Patient partners emphasized the importance of conveying how RL methods may benefit patients and the rules researchers must follow to protect the privacy and security of patient data. Other stakeholders described accuracy, flexibility, efficiency, and data security compared with other available RL solutions. Dissemination package communication products reflect the value propositions identified by key stakeholders. As prioritized by patients, the animated explainer videos emphasize the data privacy and security processes and procedures employed when performing research using RL. The RL workbook addresses researchers' and data managers' needs to iteratively design RL projects and provides accompanying resources to alleviate leadership and regulatory officials' concerns about data regulation compliance. CONCLUSION: Dissemination products to promote adoption and use of CURL include materials to facilitate patient engagement in RL research and investigator step-by-step decision-making materials about the integration of RL methods in PCOR.

Number needed to vaccinate with a COVID-19 booster to prevent a COVID-19-associated hospitalization during SARS-CoV-2 Omicron BA.1 variant predominance, December 2021-February 2022, VISION Network: a retrospective cohort study.

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.

Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19-Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions - VISION Network, September 2022-April 2023.

On September 1, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended a single bivalent mRNA COVID-19 booster dose for persons aged ≥12 years who had completed at least a monovalent primary series. Early vaccine effectiveness (VE) estimates among adults aged ≥18 years showed receipt of a bivalent booster dose provided additional protection against COVID-19-associated emergency department and urgent care visits and hospitalizations compared with that in persons who had received only monovalent vaccine doses (1); however, insufficient time had elapsed since bivalent vaccine authorization to assess the durability of this protection. The VISION Network* assessed VE against COVID-19-associated hospitalizations by time since bivalent vaccine receipt during September 13, 2022-April 21, 2023, among adults aged ≥18 years with and without immunocompromising conditions. During the first 7-59 days after vaccination, compared with no vaccination, VE for receipt of a bivalent vaccine dose among adults aged ≥18 years was 62% (95% CI = 57%-67%) among adults without immunocompromising conditions and 28% (95% CI = 10%-42%) among adults with immunocompromising conditions. Among adults without immunocompromising conditions, VE declined to 24% (95% CI = 12%-33%) among those aged ≥18 years by 120-179 days after vaccination. VE was generally lower for adults with immunocompromising conditions. A bivalent booster dose provided the highest protection, and protection was sustained through at least 179 days against critical outcomes, including intensive care unit (ICU) admission or in-hospital death. These data support updated recommendations allowing additional optional bivalent COVID-19 vaccine doses for certain high-risk populations. All eligible persons should stay up to date with recommended COVID-19 vaccines.

Effectiveness of BNT162b2 COVID-19 Vaccination in Children and Adolescents.

OBJECTIVES: We assessed BNT162b2 vaccine effectiveness (VE) against mild to moderate and severe coronavirus disease 2019 (COVID-19) in children and adolescents through the Omicron BA.4/BA.5 period. METHODS: Using VISION Network records from April 2021 to September 2022, we conducted a test-negative, case-control study assessing VE against COVID-19-associated emergency department/urgent care (ED/UC) encounters and hospitalizations using logistic regression, conditioned on month and site, adjusted for covariates. RESULTS: We compared 9800 ED/UC cases with 70 232 controls, and 305 hospitalized cases with 2612 controls. During Delta, 2-dose VE against ED/UC encounters at 12 to 15 years was initially 93% (95% confidence interval 89 to 95), waning to 77% (69% to 84%) after ≥150 days. At ages 16 to 17, VE was initially 93% (86% to 97%), waning to 72% (63% to 79%) after ≥150 days. During Omicron, VE at ages 12 to 15 was initially 64% (44% to 77%), waning to 13% (3% to 23%) after ≥150 days; at ages 16 to 17 VE was 31% (10% to 47%) during days 60 to 149, waning to 7% (-8 to 20%) after 150 days. A monovalent booster increased VE to 54% (40% to 65%) at ages 12 to 15 and 46% (30% to 58%) at ages 16 to 17. At ages 5 to 11, 2-dose VE was 49% (33% to 61%) initially and 41% (29% to 51%) after 150 days. During Delta, VE against hospitalizations at ages 12 to 17 was high (>97%), and at ages 16 to 17 remained 98% (73% to 100%) beyond 150 days; during Omicron, hospitalizations were too infrequent to precisely estimate VE. CONCLUSIONS: BNT162b2 protected children and adolescents against mild to moderate and severe COVID-19. VE was lower during Omicron predominance including BA.4/BA.5, waned after dose 2 but increased after a monovalent booster. Children and adolescents should receive all recommended COVID-19 vaccinations.

Patient and Epidemiological Factors Associated With Influenza Testing in Hospitalized Adults With Acute Respiratory Illnesses, 2016-2017 to 2019-2020.

Background: Data are limited on influenza testing among adults with acute respiratory illness (ARI)-associated hospitalizations. We identified factors associated with influenza testing in adult ARI-associated hospitalizations across the 2016-2017 through 2019-2020 influenza seasons. Methods: Using data from 4 health systems in the United States, we identified hospitalizations that had an ARI discharge diagnosis or respiratory virus test. A hospitalization with influenza testing was based on testing performed within 14 days before through 72 hours after admission. We used random forest analysis to identify patient characteristics and influenza activity indicators that were most important in terms of their relationship to influenza testing. Results: Across 4 seasons, testing rates ranged from 14.8%-19.4% at 3 pooled sites and 60.1%-78.5% at a fourth site with different testing practices. Discharge diagnoses of pneumonia or infectious disease of noninfluenza etiology, presence of ARI signs/symptoms, hospital admission month, and influenza-like illness activity level were consistently among the variables with the greatest relative importance. Conclusions: Select ARI diagnoses and indicators of influenza activity were the most important factors associated with influenza testing among ARI-associated hospitalizations. Improved understanding of which patients are tested may enhance influenza burden estimates and allow for more timely clinical management of influenza-associated hospitalizations.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

Estimation of COVID-19 mRNA Vaccine Effectiveness and COVID-19 Illness and Severity by Vaccination Status During Omicron BA.4 and BA.5 Sublineage Periods.

Importance: Recent SARS-CoV-2 Omicron variant sublineages, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 after vaccination. Objectives: To evaluate the estimated vaccine effectiveness (VE) of 2, 3, or 4 doses of COVID-19 mRNA vaccination among immunocompetent adults during a period of BA.4 or BA.5 predominant circulation; and to evaluate the relative severity of COVID-19 in hospitalized patients across Omicron BA.1, BA.2 or BA.2.12.1, and BA.4 or BA.5 sublineage periods. Design, Setting, and Participants: This test-negative case-control study was conducted in 10 states with data from emergency department (ED) and urgent care (UC) encounters and hospitalizations from December 16, 2021, to August 20, 2022. Participants included adults with COVID-19-like illness and molecular testing for SARS-CoV-2. Data were analyzed from August 2 to September 21, 2022. Exposures: mRNA COVID-19 vaccination. Main Outcomes and Measures: The outcomes of interest were COVID-19 ED or UC encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. VE associated with protection against medically attended COVID-19 was estimated, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as the reference group). Among hospitalized patients with COVID-19, demographic and clinical characteristics and in-hospital outcomes were compared across sublineage periods. Results: During the BA.4 and BA.5 predominant period, there were 82 229 eligible ED and UC encounters among patients with COVID-19-like illness (median [IQR] age, 51 [33-70] years; 49 682 [60.4%] female patients), and 19 114 patients (23.2%) had test results positive for SARS-CoV-2; among 21 007 hospitalized patients (median [IQR] age, 71 [58-81] years; 11 209 [53.4%] female patients), 3583 (17.1 %) had test results positive for SARS-CoV-2. Estimated VE against hospitalization was 25% (95% CI, 17%-32%) for receipt of 2 vaccine doses at 150 days or more after receipt, 68% (95% CI, 50%-80%) for a third dose 7 to 119 days after receipt, and 36% (95% CI, 29%-42%) for a third dose 120 days or more (median [IQR], 235 [204-262] days) after receipt. Among patients aged 65 years or older who had received a fourth vaccine dose, VE was 66% (95% CI, 53%-75%) at 7 to 59 days after vaccination and 57% (95% CI, 44%-66%) at 60 days or more (median [IQR], 88 [75-105] days) after vaccination. Among hospitalized patients with COVID-19, ICU admission or in-hospital death occurred in 21.4% of patients during the BA.1 period vs 14.7% during the BA.4 and BA.5 period (standardized mean difference: 0.17). Conclusions and Relevance: In this case-control study of COVID-19 vaccines and illness, VE associated with protection against medically attended COVID-19 illness was lower with increasing time since last dose; estimated VE was higher after receipt of 1 or 2 booster doses compared with a primary series alone.

Protection From COVID-19 mRNA Vaccination and Prior SARS-CoV-2 Infection Against COVID-19-Associated Encounters in Adults During Delta and Omicron Predominance.

BACKGROUND: Data assessing protection conferred from COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection during Delta and Omicron predominance periods in the United States are limited. METHODS: This cohort study included persons ≥18 years who had ≥1 health care encounter across 4 health systems and had been tested for SARS-CoV-2 before 26 August 2021. COVID-19 mRNA vaccination and prior SARS-CoV-2 infection defined the exposure. Cox regression estimated hazard ratios (HRs) for the Delta and Omicron periods; protection was calculated as (1-HR)×100%. RESULTS: Compared to unvaccinated and previously uninfected persons, during Delta predominance, protection against COVID-19-associated hospitalizations was high for those 2- or 3-dose vaccinated and previously infected, 3-dose vaccinated alone, and prior infection alone (range, 91%-97%, with overlapping 95% confidence intervals [CIs]); during Omicron predominance, estimates were lower (range, 77%-90%). Protection against COVID-19-associated emergency department/urgent care (ED/UC) encounters during Delta predominance was high for those exposure groups (range, 86%-93%); during Omicron predominance, protection remained high for those 3-dose vaccinated with or without a prior infection (76%; 95% CI = 67%-83% and 71%; 95% CI = 67%-73%, respectively). CONCLUSIONS: COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection provided protection against COVID-19-associated hospitalizations and ED/UC encounters regardless of variant. Staying up-to-date with COVID-19 vaccination still provides protection against severe COVID-19 disease, regardless of prior infection.

Vaccine Effectiveness Against Influenza-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2021-2022 Season, VISION Network.

BACKGROUND: Following historically low influenza activity during the 2020-2021 season, the United States saw an increase in influenza circulating during the 2021-2022 season. Most viruses belonged to the influenza A(H3N2) 3C.2a1b 2a.2 subclade. METHODS: We conducted a test-negative case-control analysis among adults ≥18 years of age at 3 sites within the VISION Network. Encounters included emergency department/urgent care (ED/UC) visits or hospitalizations with ≥1 acute respiratory illness (ARI) discharge diagnosis codes and molecular testing for influenza. Vaccine effectiveness (VE) was calculated by comparing the odds of influenza vaccination ≥14 days before the encounter date between influenza-positive cases (type A) and influenza-negative and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls, applying inverse probability-to-be-vaccinated weights, and adjusting for confounders. RESULTS: In total, 86 732 ED/UC ARI-associated encounters (7696 [9%] cases) and 16 805 hospitalized ARI-associated encounters (649 [4%] cases) were included. VE against influenza-associated ED/UC encounters was 25% (95% confidence interval (CI), 20%-29%) and 25% (95% CI, 11%-37%) against influenza-associated hospitalizations. VE against ED/UC encounters was lower in adults ≥65 years of age (7%; 95% CI, -5% to 17%) or with immunocompromising conditions (4%; 95% CI, -45% to 36%). CONCLUSIONS: During an influenza A(H3N2)-predominant influenza season, modest VE was observed. These findings highlight the need for improved vaccines, particularly for A(H3N2) viruses that are historically associated with lower VE.