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Test result management is an integral aspect of quality clinical care and a crucial part of the ambulatory medicine workflow. Correct and timely communication of results to a provider is the necessary first step in ambulatory result management and has been identified as a weakness in many paper-based systems. While electronic health records (EHRs) hold promise for improving the reliability of result management, the complexities involved make this a challenging task. Experience with test result management is reported, four new categories of result management errors identified are outlined, and solutions developed during a 2-year deployment of a commercial EHR are described. Recommendations for improving test result management with EHRs are then given. [ABSTRACT FROM AUTHOR]

Objectives: Clinical Research Informatics, an emerging sub-domain of Biomedical Informatics, is currently not well defined. A formal description of CRI including major challenges and opportunities is needed to direct progress in the field.Design: Given the early stage of CRI knowledge and activity, we engaged in a series of qualitative studies with key stakeholders and opinion leaders to determine the range of challenges and opportunities facing CRI. These phases employed complimentary methods to triangulate upon our findings.Measurements: Study phases included: 1) a group interview with key stakeholders, 2) an email follow-up survey with a larger group of self-identified CRI professionals, and 3) validation of our results via electronic peer-debriefing and member-checking with a group of CRI-related opinion leaders. Data were collected, transcribed, and organized for formal, independent content analyses by experienced qualitative investigators, followed by an iterative process to identify emergent categorizations and thematic descriptions of the data.Results: We identified a range of challenges and opportunities facing the CRI domain. These included 13 distinct themes spanning academic, practical, and organizational aspects of CRI. These findings also informed the development of a formal definition of CRI and supported further representations that illustrate areas of emphasis critical to advancing the domain.Conclusions: CRI has emerged as a distinct discipline that faces multiple challenges and opportunities. The findings presented summarize those challenges and opportunities and provide a framework that should help inform next steps to advance this important new discipline. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Computerized physician documentation (CPD) has been implemented throughout the nation's Veterans Affairs Medical Centers (VAMCs) and is likely to increasingly replace handwritten documentation in other institutions. The use of this technology may affect educational and clinical activities, yet little has been reported in this regard. The authors conducted a qualitative study to determine the perceived impacts of CPD among faculty and housestaff in a VAMC. DESIGN: A cross-sectional study was conducted using semistructured interviews with faculty (n = 10) and a group interview with residents (n = 10) at a VAMC teaching hospital. MEASUREMENTS: Content analysis of field notes and taped transcripts were done by two independent reviewers using a grounded theory approach. Findings were validated using member checking and peer debriefing. RESULTS: Four major themes were identified: (1) improved availability of documentation; (2) changes in work processes and communication; (3) alterations in document structure and content; and (4) mistakes, concerns, and decreased confidence in the data. With a few exceptions, subjects felt documentation was more available, with benefits for education and patient care. Other impacts of CPD were largely seen as detrimental to aspects of clinical practice and education, including documentation quality, workflow, professional communication, and patient care. CONCLUSION: CPD is perceived to have substantial positive and negative impacts on clinical and educational activities and environments. Care should be taken when designing, implementing, and using such systems to avoid or minimize any harmful impacts. More research is needed to assess the extent of the impacts identified and to determine the best strategies to effectively deal with them. [ABSTRACT FROM AUTHOR]

Objective: Inadequate participant recruitment is a major problem facing clinical research. Recent studies have demonstrated that electronic health record (EHR)-based, point-of-care, clinical trial alerts (CTA) can improve participant recruitment to certain clinical research studies. Despite their promise, much remains to be learned about the use of CTAs. Our objective was to study whether repeated exposure to such alerts leads to declining user responsiveness and to characterize its extent if present to better inform future CTA deployments.Methods: During a 36-week study period, we systematically documented the response patterns of 178 physician users randomized to receive CTAs for an ongoing clinical trial. Data were collected on: (1) response rates to the CTA; and (2) referral rates per physician, per time unit. Variables of interest were offset by the log of the total number of alerts received by that physician during that time period, in a Poisson regression.Results: Response rates demonstrated a significant downward trend across time, with response rates decreasing by 2.7% for each advancing time period, significantly different from zero (flat) (p<0.0001). Even after 36 weeks, response rates remained in the 30%-40% range. Subgroup analyses revealed differences between community-based versus university-based physicians (p=0.0489).Discussion: CTA responsiveness declined gradually over prolonged exposure, although it remained reasonably high even after 36 weeks of exposure. There were also notable differences between community-based versus university-based users.Conclusions: These findings add to the limited literature on this form of EHR-based alert fatigue and should help inform future tailoring, deployment, and further study of CTAs. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Potential conflicts of interest. K. N. reports payments to his institution from the National Institutes of Health; National Heart, Lung, and Blood Institute; Office of the Director, National Institutes of Health; and National Center for Advancing Translational Sciences. N. P. K. reports payments to her institution from Pfizer, Sanofi Pasteur, Merck, GSK, and Seqirus. S. A. I. reports payments to her institution from Westat Inc. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

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 to March 2023 among adults (aged ≥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 [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., Competing Interests: Potential conflicts of interest. During the conduct of the study, all Westat- and Kaiser Permanente Northern California Division of Research–affiliated authors reported receiving contractual support from the CDC via payments made to their respective institutions. Additionally, all authors affiliated with Baylor Scott & White Health, Children's Minnesota, Columbia University Irving Medical Center, HealthPartners Institute, Intermountain Healthcare, Kaiser Permanente Center for Health Research, Regenstrief Institute, University of Colorado Anschutz Medical Campus, and Vanderbilt University Medical Center reported receiving contractual support from the CDC during the conduct of the study, via subcontracts from Westat, Inc, with payments made to their respective institutions. Unrelated to the submitted work, the following disclosures were reported from the past 36 months: A. L. N. received grants from Pfizer and Vir Biotechnology; M. N. received grants directly from CDC and from CDC via subcontracts from Abt Associates and Vanderbilt University Medical Center to her institution; C. E. M. received grants AstraZeneca; S. R. received grants from GSK; and N. P. K. received research support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Seqirus. All other authors report no potential conflicts. 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 2023.)

Introduction: Phenotyping algorithms enable the interpretation of complex health data and definition of clinically relevant phenotypes; they have become crucial in biomedical research. However, the lack of standardization and transparency inhibits the cross-comparison of findings among different studies, limits large scale meta-analyses, confuses the research community, and prevents the reuse of algorithms, which results in duplication of efforts and the waste of valuable resources., Recommendations: Here, we propose five independent fundamental dimensions of phenotyping algorithms-complexity, performance, efficiency, implementability, and maintenance-through which researchers can describe, measure, and deploy any algorithms efficiently and effectively. These dimensions must be considered in the context of explicit use cases and transparent methods to ensure that they do not reflect unexpected biases or exacerbate inequities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 3 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 1862 (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., Competing Interests: Potential conflicts of interest . N. P. K. reports research support from Sanofi Pasteur and Seqirus for unrelated adult influenza vaccine effectiveness studies, and from Pfizer, Merck, and GlaxoSmithKline for unrelated studies. S. R. received funds from GlaxoSmithKline. M. G. reports a research grant and contract for the CDC Ambulatory US Flu/COVID VE Network, a grant for HAIVEN Adult Inpatient Flu/COVID VE, a contract for SYNERGY FLU/COVID study, and subcontracts for the IVY COVID/FLU VE PHS project and RECOVER-PROTECT COVID Cohort studies. D.-H. Y., L. K., M. M. D., S. W. B., and Z. A. W. report payments made to Westat via CDC contract number 200-2019-F-06819. A. B. K., A. L. N., J. A., K. D., K. N., M. B. D., M. G., N. G., P. J. E., S. A. I, S. J. G., S. R., and T. C. O. report payments made to their institution by CDC via Westat. All other authors report no potential conflicts. 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 2023.)

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., (© 2024 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: The insulin ordering process is an opportunity to provide clinicians with hypoglycemia risk predictions, but few hypoglycemia models centered around the insulin ordering process exist., Methods: We used data on adult patients, admitted in 2019 to non-ICU floors of a large teaching hospital, who had orders for subcutaneous insulin. Our outcome was hypoglycemia, defined as a blood glucose (BG) <70 mg/dL within 24 hours after ordering insulin. We trained and evaluated models to predict hypoglycemia at the time of placing an insulin order, using logistic regression, random forest, and extreme gradient boosting (XGBoost). We compared performance using area under the receiver operating characteristic curve (AUCs) and precision-recall curves. We determined recall at our goal precision of 0.30., Results: Of 21 052 included insulin orders, 1839 (9%) were followed by a hypoglycemic event within 24 hours. Logistic regression, random forest, and XGBoost models had AUCs of 0.81, 0.80, and 0.79, and recall of 0.44, 0.49, and 0.32, respectively. The most significant predictor was the lowest BG value in the 24 hours preceding the order. Predictors related to the insulin order being placed at the time of the prediction were useful to the model but less important than the patient's history of BG values over time., Conclusions: Hypoglycemia within the next 24 hours can be predicted at the time an insulin order is placed, providing an opportunity to integrate decision support into the medication ordering process to make insulin therapy safer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Potential conflicts of interest. M. G. reports additional grants or institutional contracts with the CDC Ambulatory US Flu/COVID Vaccine Effectiveness (VE) Network, Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) Adult Inpatient Flu/COVID VE, Investigating Respiratory Viruses in the Acutely Ill Public Health Surveillance Network, and Researching COVID to Enhance Recovery and Health and Human Services Protect. C. M. reports an institutional grant or contract from AstraZeneca (AZD1222) for a COVID-19 vaccination trial. A. L. N. reports institutional research funding from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and Vir Biotechnology for an unrelated influenza study. S. A. I. reports an additional pending contract with CDC (200-2012-53584, Vaccine Safety Datalink). G. V.-B. reports grants or contracts from CDC (Vaccine Safety Datalink) and Sanofi (Tdap Vaccine Safety). A. B. K. reports a subcontract through HealthPartners for VISION payment made to Children's Minnesota. B. E. D. reports a grant from the National Institutes of Health to evaluate Health Information Exchange (HIE) technologies, a grant from CDC to use HIE data for public health surveillance, an R21 grant from the US Agency for Healthcare Research and Quality to evaluate HIE technologies, a grant from the US Department of Veterans Affairs to evaluate HIE technologies, royalties from Elsevier and Springer Nature for books on HIE and public health informatics, and consulting fees for advisory panel on human papillomavirus vaccination from Merck and Co. K. M. reports 2 additional contracts with CDC (Ambulatory US Flu VE Network and HAIVEN). N. P. K. has received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. S. R. has received grant funds from GlaxoSmithKline. P. K. M., V. L., and E. B. report payments made to Westat via CDC (contract number 200-2019-F-06819). C. M., C. R., D. K., E. S., G. V.-B., J. A., J. Han., K. S. A., K. N., K. D., M. B., M. B. D., M. M., M. S. S., N. G., N. R. V., P. J. E., S. G., T. C. O., and W. F. F. report payments made to their institution by CDC via Westat. All other authors report no potential conflicts. 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 2023.)

Introduction: Research driven by real-world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID-19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants. The objective of this project was to establish privacy-preserving record linkage (PPRL) methods to ensure that patient-level EHR data remains secure and private when governance-approved linkages with other datasets occur., Methods: Separate agreements and approval processes govern N3C data contribution and data access. The Linkage Honest Broker (LHB), an independent neutral party (the Regenstrief Institute), ensures data linkages are robust and secure by adding an extra layer of separation between protected health information and clinical data. The LHB's PPRL methods (including algorithms, processes, and governance) match patient records using "deidentified tokens," which are hashed combinations of identifier fields that define a match across data repositories without using patients' clear-text identifiers., Results: These methods enable three linkage functions: Deduplication, Linking Multiple Datasets, and Cohort Discovery. To date, two external repositories have been cross-linked. As of March 1, 2023, 43 sites have signed the LHB Agreement; 35 sites have sent tokens generated for 9 528 998 patients. In this initial cohort, the LHB identified 135 037 matches and 68 596 duplicates., Conclusion: This large-scale linkage study using deidentified datasets of varying characteristics established secure methods for protecting the privacy of N3C patient data when linked for research purposes. This technology has potential for use with registries for other diseases and conditions., Competing Interests: Jasmin Phua and Sara Rogovin are employed by Datavant, Inc. and Dr. Abel Kho has a financial interest in Datavant, Inc, a for‐profit company that was contracted to provided software, expertise, and services for the creation and operation of the PPRL approach described in this manuscript. Benjamin Amor, Maya Choudhury, Philip Sparks, Amin Mannaa, and Saad Ljazouli are employed by the for‐profit Palantir Technologies, which was contracted to provided software, expertise, and services for the creation and operation of the PPRL approach described in this manuscript. At the time that this work was performed, Drs. Peter Embi, Umberto Tachinardi, and Shaun Grannis all worked for and/or served as officers of Regenstrief Institute, Inc. a non‐profit research institute contracted by the NIH to manage and oversee the PPRL and LHB work described in this manuscript., (© 2024 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

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., Competing Interests: Declaration of Competing Interest Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and from Vir Biotechnology for an unrelated influenza study.  Nicola P. Klein reports institutional support from Pfizer, Merck, GSK, Sanofi Pasteur, and Seqirus.  Manjusha Gaglani reports institutional funding from CDC for the Ambulatory US Flu/COVID VE Network and the HAIVEN Adult Inpatient Flu/COVID VE study and institutional subcontracts for the IVY-3 PHS project and RECOVER study.  All other authors have no conflicts of interest to report., (Published by Elsevier Ltd.)

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., Competing Interests: Potential conflicts of interest. A. L. N. reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy. N. P. K. reports institutional support from Pfizer, Merck, GlaxoSmithKline (GSK), Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) for unrelated studies and institutional support from Pfizer for coronavirus disease 2019 vaccine clinical trials. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential 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 for COVID-19 vaccine clinical trials. Charlene McEvoy reports institutional support from AstraZeneca for an AZD1222 COVID-19 vaccine trial. Suchitra Rao reports grant support from GlaxoSmithKline and Biofire Diagnostics. Dr. Brian Dixon reports past consulting fees from Merck & Co. for serving on an advisory panel for HPV vaccination. Manjusha Gaglani reports past support from the CDC for the IVY-3 vaccine research. Kempapura Murthy reports past support from the CDC HAIVEN – Hospitalized Adult Influenza Vaccine Effectiveness Network. All other authors report no disclosures relevant to the current manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

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., 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, GSK, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur). Allison L. Naleway reports institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy study and from Vir Biotechnology for an unrelated influenza study. Suchitra Rao reports grant support from GSK. No other potential conflicts of interest were disclosed.

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., Competing Interests: Potential conflicts of interest. S. R. received grants from GlaxoSmithKline. A. L. N. received grants from Pfizer and Vir Biotechnology. C. M. received grants from AstraZeneca. N. P. K. received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. All other authors report no potential conflicts. 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 2023.)

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. M.G. reports additional contracts with CDC Ambulatory US Flu/COVID VE Network, HAIVEN Adult Inpatient Flu/COVID VE, IVY-3 PHS, and RECOVER. A.L.N. reports research funding from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and Vir Biotechnology for an unrelated influenza study. S.A.I. reports an additional contract with Centers for Disease Control and Prevention, 200-2012-53584 (Vaccine Safety Datalink). A.K. reports a subcontract through HealthPartners for VISION payment made to Children’s Minnesota. B.E.D. reports a grant from NIH to evaluate HIE technologies, a grant from CDC to use HIE data for public health surveillance, an R21 grant from U.S. Agency for Healthcare Research Quality to evaluate HIE technologies, a grant from the U.S Department of Veterans Affairs to evaluate HIE technologies, royalties from Elsevier and Springer Nature for books on HIE and Public Health Informatics, and consulting fees for advisory panel on HPV vaccination from Merk and Co. K.M. reports two additional contracts with CDC: Ambulatory US Flu VE Network and HAIVEN Hospitalized Adult Influenza Vaccine Effectiveness Network. J.J.R., E.A.K.R., A.H., J.K., S.W.B., and M.M.D. report payments made to Westat via CDC Contract #200-2019-F-06819. B.F., E.H., E.S., K.N., K.D., C.R., C.S-A., M.B.D., T.C.O., N.G., J.N., J.A., N.R.V., and P.J.E. report payments made to their institution by CDC via Westat. No other potential conflicts of interest were disclosed.

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., Competing Interests: Potential conflicts of interest. S. A. I., M. G., K. M., and B. E. D. report institutional support from Westat. A. L. N. reports institutional support from Pfizer for a study of meningococcal B vaccine safety during pregnancy and from Vir Biotechnology for an influenza study, unrelated to the current work. K. M. reports institutional support from CDC for 2 influenza studies, unrelated to the current work. M. G. reports institutional support from CDC for 2 influenza studies and 2 COVID-19 studies, all unrelated to the current work. B. E. D. reports support from US National Institutes of Health, CDC, Agency for Healthcare Research and Quality, and Department of Veterans Affairs related to use and evaluation of health information exchange technologies; royalties from Elsevier and Springer Nature for books; and consulting fees from Merck and Co. for advisory panel on HPV vaccination. All other authors report no potential conflicts. 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 2023.)

Background: Coronavirus disease 2019 (COVID-19) vaccination coverage remains lower in communities with higher social vulnerability. Factors such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure risk and access to healthcare are often correlated with social vulnerability and may therefore contribute to a relationship between vulnerability and observed vaccine effectiveness (VE). Understanding whether these factors impact VE could contribute to our understanding of real-world VE., Methods: We used electronic health record data from 7 health systems to assess vaccination coverage among patients with medically attended COVID-19-like illness. We then used a test-negative design to assess VE for 2- and 3-dose messenger RNA (mRNA) adult (≥18 years) vaccine recipients across Social Vulnerability Index (SVI) quartiles. SVI rankings were determined by geocoding patient addresses to census tracts; rankings were grouped into quartiles for analysis., Results: In July 2021, primary series vaccination coverage was higher in the least vulnerable quartile than in the most vulnerable quartile (56% vs 36%, respectively). In February 2022, booster dose coverage among persons who had completed a primary series was higher in the least vulnerable quartile than in the most vulnerable quartile (43% vs 30%). VE among 2-dose and 3-dose recipients during the Delta and Omicron BA.1 periods of predominance was similar across SVI quartiles., Conclusions: COVID-19 vaccination coverage varied substantially by SVI. Differences in VE estimates by SVI were minimal across groups after adjusting for baseline patient factors. However, lower vaccination coverage among more socially vulnerable groups means that the burden of illness is still disproportionately borne by the most socially vulnerable populations., Competing Interests: Potential conflicts of interest. B. E. D. reported consulting fees for advisory panel on HPV vaccination from Merck & Co and book royalties from Elsevier (book on HIE) as well as Springer Nature (book on Public Health Informatics), and grant to evaluate HIE technologies from US National Institutes of Health (NIH), grant to use HIE data for public health surveillance from CDC, R21 grant to evaluate HIE technologies from US Agency for Healthcare Research and Quality, grant to evaluate HIE technologies from US Department of Veterans Affairs. G. V. B. reported grants or contracts from Sanofi for Tdap Vaccine Safety and from CDC for Vaccine Safety Datalink. A. I. N. received institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and institutional research funding from Vir Biotechnology for unrelated influenza study. S. Rao received grant funding from GlaxoSmithKline. S. A. I. reports contract no. 200-2012-53584 (Vaccine Safety Datalink) from CDC. M. B. reports Columbia University is part of the VISION surveillance network and receives funding from Westat to support work done at Columbia as part of VISION. M. G. reports Ambulatory US Flu/COVID VE Network institutional grant, HAIVEN Adult Inpatient Flu/COVID VE institutional grant from CDC, IVY-3 PHS project institutional subcontract from CDC-Vanderbilt, and RECOVER study institutional subcontract from CDC-Abt. K. M. reports contracts or grants paid to institution from US CDC Ambulatory US Flu VE Network and US CDC HAIVEN—Hospitalized Adult Influenza Vaccine Effectiveness Network. All other authors report no potential conflicts. 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 2023.)

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., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: We assessed coronavirus disease 2019 (COVID-19) vaccination impact on illness severity among adults hospitalized with COVID-19, August 2021-March 2022., Methods: We evaluated differences in intensive care unit (ICU) admission, in-hospital death, and length of stay among vaccinated (2 or 3 mRNA vaccine doses) versus unvaccinated patients aged ≥18 years hospitalized for ≥24 hours with COVID-19-like illness and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular testing. We calculated odds ratios (ORs) for ICU admission and death and subdistribution hazard ratios (SHR) for time to hospital discharge adjusted for age, geographic region, calendar time, and local virus circulation., Results: We included 27 149 SARS-CoV-2-positive hospitalizations. During both Delta- and Omicron-predominant periods, protection against ICU admission was strongest among 3-dose vaccinees compared with unvaccinated patients (Delta OR, 0.52 [95% CI, .28-.96]; Omicron OR, 0.69 [95% CI, .54-.87]). During both periods, risk of in-hospital death was lower among vaccinated compared with unvaccinated patients but ORs overlapped across vaccination strata. We observed SHR >1 across all vaccination strata in both periods indicating faster discharge for vaccinated patients., Conclusions: COVID-19 vaccination was associated with lower rates of ICU admission and in-hospital death in both Delta and Omicron periods compared with being unvaccinated., Competing Interests: Potential conflicts of interest. N. P. K. reported receiving grants from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur) outside the submitted work. B. E. D. reported consulting fees for advisory panel on HPV vaccination from Merck & Co and book royalties from Elsevier as well as Springer Nature. A. L. N. received institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy and from Vir Biotechnology for an unrelated influenza study. S. R. received grant funding from GlaxoSmithKline. C. M. received institutional support from AstraZeneca for a COVID vaccine trial. G. V.-B. reported Sanofi for Tdap Vaccine Safety. M. G. reported receiving institutional support from CDC for the ambulatory US Flu/COVID VE network and HAIVEN adult inpatient flu/COVID VE network; from CDC-Vanderbilt for the IVY-3 PHS project and from CDC-Abt for the RECOVER study. All other authors declare no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. 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.)

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., 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 received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. Allison L. Naleway received grants from Pfizer and Vir Biotechnology. Suchitra Rao received grants from GlaxoSmithKline. Charlene McEvoy received grants from AztraZeneca. No other potential conflicts of interest were disclosed.

Background: As diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States., Methods: Six health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2., Results: Across datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis., Conclusion: Our results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Natalie E Sheils is an employee of Optum Labs and owns stock in the parent company UnitedHealth group. Anthony M Louder is a paid employee of Aetion and hold Aetion stock options. Nancy D. Lin was an employee of Health Catalyst at the time the work was performed. Jennifer Gatz is a full-time employee of Regenstrief Institute, which provides independent research services to entities including those within the pharmaceutical and medical device industries. Shaun J. Grannis serves as Chief Medical Information Officer for the Indiana Health Information Exchange, and is a founding partner of Uppstroms, LLC. Carly Kabelac is a paid employee of Aetion and hold Aetion stock options. Carrie L. Byington has intellectual property in and receives royalties from BioFire, Inc. She serves as a scientific advisor to IDbyDNA (San Francisco, CA and Salt Lake City, UT). Dr. Byington is on the Board of the Commonwealth Fund. Atul J. Butte is a co-founder and consultant to Personalis and NuMedii; consultant to Samsung, Mango Tree Corporation, and in the recent past, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Facebook, Alphabet (Google), Microsoft, Amazon, Snap, Snowflake, 10x Genomics, Illumina, Nuna Health, Assay Depot (Scientist.com), Vet24seven, Regeneron, Sanofi, Royalty Pharma, Pfizer, BioNTech, AstraZeneca, Moderna, Biogen, Twist Bioscience, Pacific Biosciences, Editas Medicine, Invitae, Doximity, and Sutro, and several other non-health related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, several investment and venture capital firms, and many academic institutions, medical or disease specific foundations and associations, and health systems. Atul Butte receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. Carla Rodriguez-Watson receives research support from Merck, Novartis, Pfizer, Lilly, Janssen, and AbbVie. She holds minor stock in Gilead., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation., Methods: Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters., Results: A total of 15,615 people were observed to have at least one serology test 14-90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79-96%) compared to non-Hispanic (60-89%) patients; in those presenting with at least one COVID-19 related symptom (69-93%) as compared to no such symptoms (63-91%); and in inpatient (70-97%) and emergency department (93-99%) compared to outpatient (63-92%) settings across datasets. PPA was highest in those with diabetes (75-94%) and kidney disease (83-95%); and lowest in those with auto-immune conditions or who are immunocompromised (56-93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59-3.86), patients with diabetes (1.49-1.56), and obesity (1.63-2.23); and lower in those with immunocompromised or autoimmune conditions (0.25-0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets., Conclusion: Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests., Competing Interests: AJB is a co-founder and consultant to Personalis and NuMedii; consultant to Samsung, Mango Tree Corporation, and in the recent past, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Facebook, Alphabet (Google), Microsoft, Amazon, Snap, Snowflake, 10x Genomics, Illumina, Nuna Health, Assay Depot (Scientist.com), Vet24seven, Regeneron, Sanofi, Royalty Pharma, Pfizer, BioNTech, AstraZeneca, Moderna, Biogen, Twist Bioscience, Pacific Biosciences, Editas Medicine, Invitae, Doximity, and Sutro, and several other non-health related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, several investment and venture capital firms, and many academic institutions, medical or disease specific foundations and associations, and health systems. AJB receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. AJB’s research has been funded by NIH, Northrup Grumman (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor’s Office of Planning and Research, California Institute for Regenerative Medicine, L’Oreal, and Progenity. CLB has intellectual property in and receives royalties from BioFire, Inc. She serves as a scientific advisor to IDbyDNA (San Francisco, CA and Salt Lake City, UT); and is on the Board of the Commonwealth Fund. CK is a paid employee of Aetion and hold Aetion stock options. NES is an employee of Optum Labs and owns stock in the parent company UnitedHealth group. NDL was an employee of Health Catalyst at the time the work was performed. JLG is a full-time employee of Regenstrief Institute, which provides independent research services to entities including those within the pharmaceutical and medical device industries. SJG serves as Chief Medical Information Officer for the Indiana Health Information Exchange, and is a founding partner of Uppstroms, LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Watson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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, 31% 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 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% 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., 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 received grants from Pfizer, Merck, GlaxoSmithKline, and Sanofi Pasteur. Allison L. Naleway received grants from Pfizer and Vir Biotechnology. Suchitra Rao received grants from GlaxoSmithKline. Charlene McEvoy received grants from AztraZeneca. No other potential conflicts of interest were disclosed.

Persons with moderate-to-severe immunocompromising conditions might have reduced protection after COVID-19 vaccination, compared with persons without immunocompromising conditions (1-3). On August 13, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended that adults with immunocompromising conditions receive an expanded primary series of 3 doses of an mRNA COVID-19 vaccine. ACIP followed with recommendations on September 23, 2021, for a fourth (booster) dose and on September 1, 2022, for a new bivalent mRNA COVID-19 vaccine booster dose, containing components of the BA.4 and BA.5 sublineages of the Omicron (B.1.1.529) variant (4). Data on vaccine effectiveness (VE) of monovalent COVID-19 vaccines among persons with immunocompromising conditions since the emergence of the Omicron variant in December 2021 are limited. In the multistate VISION Network, § monovalent 2-, 3-, and 4-dose mRNA VE against COVID-19-related hospitalization were estimated among adults with immunocompromising conditions ¶ hospitalized with COVID-19-like illness,** using a test-negative design comparing odds of previous vaccination among persons with a positive or negative molecular test result (case-patients and control-patients) for SARS-CoV-2 (the virus that causes COVID-19). During December 16, 2021-August 20, 2022, among SARS-CoV-2 test-positive case-patients, 1,815 (36.3%), 1,387 (27.7%), 1,552 (31.0%), and 251 (5.0%) received 0, 2, 3, and 4 mRNA COVID-19 vaccine doses, respectively. Among test-negative control-patients during this period, 6,928 (23.7%), 7,411 (25.4%), 12,734 (43.6%), and 2,142 (7.3%) received these respective doses. Overall, VE against COVID-19-related hospitalization among adults with immunocompromising conditions hospitalized for COVID-like illness during Omicron predominance was 36% ≥14 days after dose 2, 69% 7-89 days after dose 3, and 44% ≥90 days after dose 3. Restricting the analysis to later periods when Omicron sublineages BA.2/BA.2.12.1 and BA.4/BA.5 were predominant and 3-dose recipients were eligible to receive a fourth dose, VE was 32% ≥90 days after dose 3 and 43% ≥7 days after dose 4. Protection offered by vaccination among persons with immunocompromising conditions during Omicron predominance was moderate even after a 3-dose monovalent primary series or booster dose. Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP recommendations. Further, additional protective recommendations for persons with immunocompromising conditions, including the use of prophylactic antibody therapy, early access to and use of antivirals, and enhanced nonpharmaceutical interventions such as well-fitting masks or respirators, should also be considered., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Brian E. Dixon reported grant support from the National Institutes of Health, Agency for Healthcare Research and Quality, and the U.S. Department of Veterans Affairs; personal fees from Elsevier and Springer Nature; and consulting fees from Merck. Nicola P. Klein reported institutional grant support from Pfizer, Inc., Merck, GSK, and Sanofi Pasteur. Allison L. Naleway reported institutional support from Pfizer, Inc. and Vir Biotechnology. Suchitra Rao reported grant support from GSK. Charlene McEvoy reported institutional support from AstraZeneca. No other potential conflicts of interest were disclosed.

Objective: To estimate the effectiveness of mRNA vaccines against moderate and severe covid-19 in adults by time since second, third, or fourth doses, and by age and immunocompromised status., Design: Test negative case-control study., Setting: Hospitals, emergency departments, and urgent care clinics in 10 US states, 17 January 2021 to 12 July 2022., Participants: 893 461 adults (≥18 years) admitted to one of 261 hospitals or to one of 272 emergency department or 119 urgent care centers for covid-like illness tested for SARS-CoV-2., Main Outcome Measures: The main outcome was waning of vaccine effectiveness with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine during the omicron and delta periods, and the period before delta was dominant using logistic regression conditioned on calendar week and geographic area while adjusting for age, race, ethnicity, local virus circulation, immunocompromised status, and likelihood of being vaccinated., Results: 45 903 people admitted to hospital with covid-19 (cases) were compared with 213 103 people with covid-like illness who tested negative for SARS-CoV-2 (controls), and 103 287 people admitted to emergency department or urgent care with covid-19 (cases) were compared with 531 168 people with covid-like illness who tested negative for SARS-CoV-2. In the omicron period, vaccine effectiveness against covid-19 requiring admission to hospital was 89% (95% confidence interval 88% to 90%) within two months after dose 3 but waned to 66% (63% to 68%) by four to five months. Vaccine effectiveness of three doses against emergency department or urgent care visits was 83% (82% to 84%) initially but waned to 46% (44% to 49%) by four to five months. Waning was evident in all subgroups, including young adults and individuals who were not immunocompromised; although waning was morein people who were immunocompromised. Vaccine effectiveness increased among most groups after a fourth dose in whom this booster was recommended., Conclusions: Effectiveness of mRNA vaccines against moderate and severe covid-19 waned with time after vaccination. The findings support recommendations for a booster dose after a primary series and consideration of additional booster doses., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: NPK 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. CM received institutional support from AstraZeneca for a covid-19 vaccine trial. ALN received institutional support from Pfizer for an unrelated study of meningococcal B vaccine safety during pregnancy. SR received grant funding from GlaxoSmithKline and Biofire Diagnostics. Authors declare no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate changes in public mask-wearing behavior in response to public health policies during COVID-19., Design: Panel of observed public mask-wearing., Setting: Counts of adult behavior in Marion County, Indiana, between November 15, 2020, and May 31, 2021., Determinants of Interest: (1) Removal of state masking requirement; (2) introduction of the National Strategy for the COVID-19 Response and Pandemic Preparedness; (3) the Centers for Disease Control and Prevention (CDC) recommendation that vaccinated individuals did not need to wear masks in public; and (4) COVID-19 vaccine availability., Outcome: Percent observed with correct mask-wearing., Analyses: Fixed-effects models estimated the association between policies and mask-wearing., Results: Ending Indiana's mask requirement was not associated with changes in correct mask-wearing. The CDC's recommendation was associated with a decrease of 12.3 percentage points in correct mask-wearing (95% CI, -23.47 to -1.05; P = .032)., Conclusions: Behavior encouraged by local mask requirements appeared to be resilient to changes in state policy. CDC recommendations appeared influential., Competing Interests: Dr Embi is the inventor of the MaskCount Web-based app used in this study, developed with support from the Regenstrief Institute, Inc, and otherwise has nothing to disclose. Dr Vest is a founder and equity holder in Uppstroms, LLC, a technology company. Drs Cash-Goldwasser, Peters Bergquist, Virginia Caine, and Halverson declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)

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.

The growing availability of multi-scale biomedical data sources that can be used to enable research and improve healthcare delivery has brought about what can be described as a healthcare "data age." This new era is defined by the explosive growth in bio-molecular, clinical, and population-level data that can be readily accessed by researchers, clinicians, and decision-makers, and utilized for systems-level approaches to hypothesis generation and testing as well as operational decision-making. However, taking full advantage of these unprecedented opportunities presents an opportunity to revisit the alignment between traditionally academic biomedical informatics (BMI) and operational healthcare information technology (HIT) personnel and activities in academic health systems. While the history of the academic field of BMI includes active engagement in the delivery of operational HIT platforms, in many contemporary settings these efforts have grown distinct. Recent experiences during the COVID-19 pandemic have demonstrated greater coordination of BMI and HIT activities that have allowed organizations to respond to pandemic-related changes more effectively, with demonstrable and positive impact as a result. In this position paper, we discuss the challenges and opportunities associated with driving alignment between BMI and HIT, as viewed from the perspective of a learning healthcare system. In doing so, we hope to illustrate the benefits of coordination between BMI and HIT in terms of the quality, safety, and outcomes of care provided to patients and populations, demonstrating that these two groups can be "better together.", Competing Interests: The authors have no competing interests to declare., (© 2022 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

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.

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.

Development of evidence-based practice requires practice-based evidence, which can be acquired through analysis of real-world data from electronic health records (EHRs). The EHR contains volumes of information about patients-physical measurements, diagnoses, exposures, and markers of health behavior-that can be used to create algorithms for risk stratification or to gain insight into associations between exposures, interventions, and outcomes. But to transform real-world data into reliable real-world evidence, one must not only choose the correct analytical methods but also have an understanding of the quality, detail, provenance, and organization of the underlying source data and address the differences in these characteristics across sites when conducting analyses that span institutions. This manuscript explores the idiosyncrasies inherent in the capture, formatting, and standardization of EHR data and discusses the clinical domain and informatics competencies required to transform the raw clinical, real-world data into high-quality, fit-for-purpose analytical data sets used to generate real-world evidence., Competing Interests: None of the authors have any conflicts of interest to report nor received any funding in support of the manuscript development., (© 2021 The Authors. Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Youth in the justice system (YJS) are more likely than youth who have never been arrested to have mental health and substance use problems. However, a low percentage of YJS receive SUD services during their justice system involvement. The SUD care cascade can identify potential missed opportunities for treatment for YJS. Steps along the continuum of the cascade include identification of treatment need, referral to services, and treatment engagement. To address gaps in care for YJS, we will (1) implement a learning health system (LHS) to develop, or improve upon, alliances between juvenile justice (JJ) agencies and community mental health centers (CMHC) and (2) present local cascade data during continuous quality improvement cycles within the LHS alliances., Methods/design: ADAPT is a hybrid Type II effectiveness implementation trial. We will collaborate with JJ and CMHCs in eight Indiana counties. Application of the EPIS (exploration, preparation, implementation, and sustainment) framework will guide the implementation of the LHS alliances. The study team will review local cascade data quarterly with the alliances to identify gaps along the continuum. The study will collect self-report survey measures longitudinally at each site regarding readiness for change, implementation climate, organizational leadership, and program sustainability. The study will use the Stages of Implementation Completion (SIC) tool to assess the process of implementation across interventions. Additionally, the study team will conduct focus groups and qualitative interviews with JJ and CMHC personnel across the intervention period to assess for impact., Discussion: Findings have the potential to increase SUD need identification, referral to services, and treatment for YJS., (Copyright © 2021. Published by Elsevier Inc.)

Background: Early studies on COVID-19 identified unequal patterns in hospitalization and mortality in urban environments for racial and ethnic minorities. These studies were primarily single center observational studies conducted within the first few weeks or months of the pandemic. We sought to examine trends in COVID-19 morbidity, hospitalization, and mortality over time for minority and rural populations, especially during the U.S. fall surge., Methods: Data were extracted from a statewide cohort of all adult residents in Indiana tested for SARS-CoV-2 infection between March 1 and December 31, 2020, linked to electronic health records. Primary measures were per capita rates of infection, hospitalization, and death. Age adjusted rates were calculated for multiple time periods corresponding to public health mitigation efforts. Comparisons across time within groups were compared using ANOVA., Results: Morbidity and mortality increased over time with notable differences among sub-populations. Initially, hospitalization rates among racial minorities were 3-4 times higher than whites, and mortality rates among urban residents were twice those of rural residents. By fall 2020, hospitalization and mortality rates in rural areas surpassed those of urban areas, and gaps between black/brown and white populations narrowed. Changes across time among demographic groups was significant for morbidity and hospitalization. Cumulative morbidity and mortality were highest among minority groups and in rural communities., Conclusions: The synchronicity of disparities in COVID-19 by race and geography suggests that health officials should explicitly measure disparities and adjust mitigation as well as vaccination strategies to protect those sub-populations with greater disease burden., Competing Interests: The authors have declared that no competing interests exist.

Objective: We sought to support public health surveillance and response to coronavirus disease 2019 (COVID-19) through rapid development and implementation of novel visualization applications for data amalgamated across sectors., Materials and Methods: We developed and implemented population-level dashboards that collate information on individuals tested for and infected with COVID-19, in partnership with state and local public health agencies as well as health systems. The dashboards are deployed on top of a statewide health information exchange. One dashboard enables authorized users working in public health agencies to surveil populations in detail, and a public version provides higher-level situational awareness to inform ongoing pandemic response efforts in communities., Results: Both dashboards have proved useful informatics resources. For example, the private dashboard enabled detection of a local community outbreak associated with a meat packing plant. The public dashboard provides recent trend analysis to track disease spread and community-level hospitalizations. Combined, the tools were utilized 133 637 times by 74 317 distinct users between June 21 and August 22, 2020. The tools are frequently cited by journalists and featured on social media., Discussion: Capitalizing on a statewide health information exchange, in partnership with health system and public health leaders, Regenstrief biomedical informatics experts rapidly developed and deployed informatics tools to support surveillance and response to COVID-19., Conclusions: The application of public health informatics methods and tools in Indiana holds promise for other states and nations. Yet, development of infrastructure and partnerships will require effort and investment after the current pandemic in preparation for the next public health emergency., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)