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Background: Influenza vaccination of adults remains below recommended levels. Standing orders programs (SOPs) that allow nonphysician medical staff to assess eligibility and administer vaccines without an individualized physician's order are a proven method to increase vaccination rates. However, recent data on their use are not available.Purpose: Investigators surveyed primary care physicians nationwide in 2009 to assess factors related to awareness and use of SOPs.Methods: Using the AMA Master List, a stratified random sample of U.S. family physicians (n=820) and general internists (n=820) was selected to receive a mailed questionnaire. The inclusion criterion was providing primary care to adults in an office-based practice. The primary outcome measure, analyzed in 2010, was consistent use of SOPs.Results: The survey response rate was 67% (1015/1517). Forty-two percent of respondents who immunized adults in their practices reported consistent use of SOPs. Those physicians differed in several dimensions, including awareness of recommendations and regulations regarding SOPs for vaccines, size and type of practice, number and level of training of clinical staff, attributes of the staff. The two variables in logistic regression models that were associated with the highest likelihood of using SOPs were awareness of recommendations to use them (OR=3.0; 95% CI=2.2, 4.1) and agreement with their effectiveness (OR=2.7, 95% CI=1.9, 3.8).Conclusions: Fewer than half of physicians report using SOPs for influenza vaccination, a number that is not much higher than it was about a decade ago. Approaches to increase use of SOPs are needed. [ABSTRACT FROM AUTHOR]

Racial disparities in invasive pneumococcal disease and pneumococcal polysaccharide vaccination (PPV) persist despite significant progress. One reason may be that minority patients receive primary care at practices with fewer resources, less efficient office systems, and different priorities. The purposes of this paper are: (1) to describe the recruitment of a diverse array of primary care practices in Pittsburgh, Pennsylvania serving white and minority patient populations, and the multimodal data collection process that included surveys of key office personnel, observations of practice operations and medical record reviews for determining PPV vaccination rates; and (2) to report the results of the sampling strategy. During 2005, 18 practices participated in the study, six with a predominantly minority patient population, nine with a predominantly white patient population, and three with a racial distribution similar to that of this locality. Eight were solo practices and 10 were multiprovider practices; they included federally qualified health centers, privately owned practices and faculty and University of Pittsburgh Medical Center community practices. Providers represented several racial and ethnic groups, as did office staffs. PPV rates determined from 2,314 patients' medical records averaged 60.3 +/- 22.6% and ranged from 11% to 97%. Recruitment of practices with attention to location, patient demographics, and provider types results in a diverse sample of practices and patients. Multimodal data collection from these practices should provide a rich data source for examining the complex interplay of factors affecting immunization disparities among older adults. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pneumococcal polysaccharide vaccination rates among adults 65 years and older or less than 65 years with high risk medical conditions are still below Healthy People 2010 recommended levels of 90%. This study was designed to: 1) assess self-reported pneumococcal vaccination rates following health center level interventions to increase adult vaccination rates; and 2) determine factors associated with vaccination. METHODS: Tailored interventions to increase immunizations were implemented at two inner-city health centers. We surveyed 375 patients 50 years of age and older. Multivariate logistic regression examines the predictors of 1) self-reported pneumococcal vaccination and 2) combined self-reported influenza and pneumococcal vaccination. Both of these models were stratified by age group (50-64 years and 65 years and older). RESULTS: Pneumococcal vaccination rates were 45% by self-report, 55% by medical record review, 69% for patients 65 years old and older, 32% for patients 50-64 years; they did not differ by race. Receipt of the previous season's influenza vaccine was significantly related to pneumococcal vaccination among both younger and older patients. Receiving both the pneumococcal vaccine and the most recent influenza vaccine compared with receiving neither, among younger patients was related to unemployment, more frequent physician visits, and belief that those who do not receive the flu shot are more susceptible to the flu. For older patients, receipt of both vaccines was related to nonsmoking status, believing that friends/family think the patient should be vaccinated, seeing posters advertising flu shot clinics, and belief that those who do not receive the flu shot are more susceptible to the flu. CONCLUSION: Our findings suggest that improving overall pneumococcal vaccination rates among eligible adults, has the potential to eliminate racial disparities. Interventions delivering vaccination messages specific to older and younger adult groups may be the best strategy for improving adult vaccination rates. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To identify facilitators of and barriers to vaccination in patients from a range of socioeconomic levels. DESIGN: A survey was conducted in 2001 using computer-assisted telephone interviewing. SETTING: Patients from inner-city health centers and suburban practices were interviewed. PARTICIPANTS: Inclusion criteria were aged 66 and older and an office visit after September 30, 1998. MEASUREMENTS: Self-reported influenza and pneumococcal vaccination status and facilitating conditions, attitudes, social influences, and perceived consequences from the Triandis model were assessed. RESULTS: Overall, 557 interviews were completed with 775 eligible patients (72%). Patients who reported having received pneumococcal vaccine more frequently believed that their physicians recommended the vaccine than did the unvaccinated (97% vs 49%; P=.001). This was also true for influenza vaccine (99% vs 80%; P<.001). More unvaccinated patients than vaccinated patients felt that obtaining either vaccine was more trouble than it is worth (pneumococcal 19% vs 1%; P=.04, influenza 20% vs 1%; P=.004). The vaccinated were more likely to be willing to obtain the influenza and pneumococcal vaccines at the same time (pneumococcal 91% vs 59%; P=.002, influenza 91% vs 55%; P=.014). CONCLUSION: Physicians should take every opportunity to recommend vaccination to their eligible adult patients. Offering influenza and pneumococcal vaccines at the same visit is an acceptable means to ensure that adults are fully vaccinated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Started in late 1994, the Vaccines for Children (VFC) program is a major entitlement program that provides states with free vaccines for disadvantaged children. Some evaluation studies have been conducted, but they do not include individually matched pre-post comparisons of physician responses. This project studied the effect of the VFC on the physician likelihood of referring children to public vaccine clinics for immunizations. DESIGN: In 1999, trained personnel conducted a survey of a cohort of physicians who previously participated in surveys on barriers to childhood vaccination conducted before VFC implementation. Responses were matched, and pre- versus post-VFC comparisons were made. SETTING AND PARTICIPANTS: Minnesota and Pennsylvania primary care physicians selected by stratified random sampling and initially studied in 1990 to 1991 and 1993, respectively. MAIN OUTCOME MEASURES: Likelihood of referral of a child to a public vaccine clinic. RESULTS: On a scale of 0 to 10, physician likelihood of referring an uninsured child decreased by a mean of 1.9 (95% confidence interval: 1.2-2.5) from pre- to post-VFC. Two fifths (45%) of physicians reported that the VFC decreased the number of referrals from their practice to public vaccine clinics and 50% gave intermediate responses. Among physicians who participate in VFC, only 9% were likely to refer a Medicaid-insured child in contrast to 44% of those not participating. CONCLUSIONS: Physicians' reported referral and likelihood of referring Medicaid-insured and uninsured children has decreased because of VFC in Minnesota and Pennsylvania.vaccination/economics, vaccination/legislation and jurisprudence, immunization programs/economics, immunization programs/utilization, vaccines/economics, Medicaid/economics, national health programs United States, child health services. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae causes approximately 3,300 cases of meningitis, 100,000 to 135,000 cases of pneumonia requiring hospitalization and 6 million cases of otitis media annually in the United States. Pneumococcal conjugate vaccine, approved in 2000 for use in the United States, was designed to cover the seven serotypes that account for about 80 percent of invasive infections in children younger than six years. This vaccine demonstrated 100 percent efficacy against invasive pneumococcal disease in the primary analysis of a large randomized, double-blind, controlled trial. In the follow-up analysis, performed eight months after the trial ended, efficacy against invasive disease was found to be 94 percent for the included serotypes. When initiated during infancy, the four-dose vaccination schedule is set at two, four, six and 12 to 15 months of age. The American Academy of Family Physicians recommends routine vaccination of infants, catch-up vaccination of children younger than 24 months and catch-up vaccination of children 24 to 59 months of age with high-risk medical conditions such as sickle cell disease and congenital heart disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Concerns about financial barriers to vaccination led to the creation of the Vaccines for Children (VFC) program, which provides free vaccines to states for disadvantaged children. Our objective was to understand the effect of free vaccine and insurance on pediatric nurse practitioners' (PNPs) likelihood of referring children to public vaccine clinics. Although referral from the medical home to public vaccine clinics is preferable to not vaccinating, there are disadvantages, including the potential for windows of inadequate protection and fragmentation of care. METHODS: A standardized survey was conducted by trained personnel using computer-assisted telephone interviewing. We interviewed a national random sample of primary care PNPs in 1997. RESULTS: In 1997, 252 of 271 (93%) directly contacted PNPs were interviewed. The percentage of respondents receiving free vaccines was 82%. Among PNPs not receiving free vaccines, the percentages stating that they were likely to refer insured, Medicaid insured, and uninsured children to public vaccine clinics were 7%, 27%, and 67%, respectively. In contrast, among PNPs receiving free vaccines, only 46% would refer an uninsured child and 10% a Medicaid child. CONCLUSIONS: Most respondents received free vaccine supplies in 1997. Based on current PNP data and previous physician data, most clinicians who do not receive free vaccine supplies are likely to refer uninsured children to public vaccine clinics. In contrast, clinicians who receive free vaccine supplies are much more likely to vaccinate uninsured and Medicaid-insured children. [ABSTRACT FROM AUTHOR]

The American Academy of Family Physicians now recommends that all persons 50 years of age and older receive an annual influenza vaccination, because the rates of morbidity and mortality associated with influenza are high and vaccination is cost-effective. Reasons for lowering the recommended age for routine vaccination from 65 to 50 years of age include reductions in office visits, hospitalizations, time taken off work and associated costs. In working adults 18 to 64 years of age, the cost savings were estimated at $46.85 per person vaccinated. Furthermore, the fatality rate from influenza begins to rise at age 45 and is highest in persons with multiple chronic medical conditions. As in the past, recommendations target persons at high risk for complications, such as those with cardiac disease, lung disease and diabetes, as well as health care workers and residents of nursing homes. Severe allergy to eggs is a contraindication to influenza vaccination. [ABSTRACT FROM AUTHOR]

As a result of the success of immunization, indigenous wild poliomyelitis has disappeared from the United States. Of 142 confirmed cases of paralytic poliomyelitis reported in the United States from 1980 to 1996, 134 were classified as vaccine-associated paralytic poliomyelitis (VAPP). Persons with VAPP have a disabling illness, and this has caught the attention of the lay media. The risk of VAPP is one case per 750,000 doses distributed for the first dose of oral poliovirus vaccine (OPV) and one case per 2.4 million doses of OPV distributed overall. Because of this risk, most parents prefer a vaccine schedule that starts with inactivated poliovirus vaccine (IPV), even though extra injections are required. IPV does not cause VAPP. New studies show that high immunization rates can be achieved in disadvantaged populations with a schedule starting with IPV. The American Academy of Family Physicians now recommends that the first two doses of poliovirus vaccine should be IPV; that is, either an all-IPV schedule or a sequential schedule of two doses of IPV followed by two doses of OPV. OPV is no longer recommended for the first two doses and is acceptable only under special circumstances, such as when parents do not accept the recommended number of injections. [ABSTRACT FROM AUTHOR]

Context: Vaccines are underused in the United States, resulting in needless morbidity. Many experts have concluded that clinician education is critical to increasing the nation's vaccination rates.Objective: To develop and evaluate case-based curricular materials on immunizations that promote preventive medicine skills.Design: Before-and-after trial of an educational intervention.Setting and Participants: Medical schools and primary care residency programs from 20 institutions across the United States participated in the Teaching Immunization for Medical Education (TIME) project.Intervention: A multidisciplinary team developed learning objectives, abstracted clinical cases, and created case-based modules that use contextual learning and small-group interaction to solve clinical and public health problems. The case-based methods are multistation clinical teaching scenarios (MCTS) and problem-based learning (PBL).Main Outcome Measures: Knowledge gained by learners from pretest to posttest and the overall ratings of the sessions by learners and facilitators based on evaluation questionnaires.Results: Pretest and posttest results were obtained on a total of 1122 learners for all modules combined. For the MCTS method, mean scores increased from the 10-item pretest to the posttest by 3.1 items for measles, 3.8 for influenza, 1.8 for hepatitis B, 3.9 for pertussis, 1.9 for adult vaccination, 1.9 for childhood vaccination, and 2.6 for Haemophilus influenzae type b (P<.01 for each). For the PBL method, mean scores increased by 3.4 items for measles, 3.3 for influenza, 2.6 for hepatitis B, and 2.5 for pertussis (P<.01 for each). Most learners (MCTS, 98%; PBL, 89%) and most facilitators (MCTS, 97%; PBL, 100%) rated the sessions overall as very good or good.Conclusions: Use of TIME modules increases knowledge about immunizations, an essential step to improving vaccination practices of future clinicians. Given the realities of decreased faculty time and budgets, educators face major challenges in developing case-based curricula that prepare learners for the 21st century. Nationally tested libraries of cases such as the TIME modules address this dilemma. [ABSTRACT FROM AUTHOR]

Background: A substantial delay in distribution of influenza vaccine occurred in the 2000-2001 influenza season. Our objective was to quantify the impact of this delay on immunization rates, location of receipt of immunization, and patient attitudes and beliefs about the influenza vaccine.Methods: Inner-city and suburban medical practices that received influenza vaccine supply on-time or late in the season (late-receipt) were selected. A random sample of elderly patients from each practice completed telephone interviews.Results: Of 775 eligible patients, we interviewed 72%. The odds of receiving influenza vaccine in late-receipt practices compared to on-time practices did not significantly differ in either the suburban stratum (adjusted OR = 0.9, 95% CI 0.5-1.6) or the inner-city stratum (adjusted OR = 1.5, 95% CI 0.8-2.8). Very few respondents (4%-11%) reported changes in their beliefs about the vaccine, its safety or efficacy, from previous years. More patients in late-receipt practices reported receiving influenza vaccine at locations other than their regular doctor's offices in the shortage year compared with the previous year.Conclusions: The 2000-2001 influenza vaccine delay changed vaccination location, but did not change influenza vaccination rates. [ABSTRACT FROM AUTHOR]

PURPOSE: An inpatient pneumococcal polysaccharide vaccine (PPV) vaccination program was designed and implemented to meet federal and state regulatory requirements and national vaccination goals. SUMMARY: In 2002, the Centers for Medicare and Medicaid Services published a final rule removing the federal requirement for an individual patient physician-signed order for the pneumococcal and influenza vaccines in Medicare- and Medicaid- participating hospitals. This statute authorized implementation of standing orders programs (SOPs) in health care institutions. At the University of Pittsburgh Medical Center-Presbyterian (UPMC-P), institutional vaccination rates and the existing mechanism for providing adult vaccinations were evaluated. At the peak of the program's effectiveness in 2000, in-hospital total vaccination rates were 31%; those rates fell to 15% by the end of 2003. To rectify this poor rate of vaccination, a multidisciplinary team convened to evaluate the existing program and to design the tools and processes for a conversion to a vaccine SOP. A standing order form was designed, and it was determined that the SOP should be pharmacy driven. As a result of the SOP, the PPV vaccination rate increased dramatically; in 2005, the average rate was 69%, with the highest rate occurring in March 2005 (87%). CONCLUSION: The cooperative effort of a multidisciplinary work group including physicians, nursing staff, and pharmacy personnel led to the creation of a successful inpatient PPV SOP. Analysis of the previous vaccination program and careful planning were instrumental in designing the SOP. Defined responsibilities for daily performance and user-friendly tools with clear instructions were also crucial to the success of the program. [ABSTRACT FROM AUTHOR]

Background: In December 2009, when the H1N1 influenza pandemic appeared to be subsiding, public health officials and unvaccinated individuals faced the question of whether continued H1N1 immunization was still worthwhile.Purpose: To delineate what combinations of possible mechanisms could generate a third pandemic wave and then explore whether vaccinating the population at different rates and times would mitigate the wave.Methods: As part of ongoing work with the Office of the Assistant Secretary for Preparedness and Response at the USDHHS during the H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agent Study team employed an agent-based computer simulation model of the Washington DC metropolitan region to delineate what mechanisms could generate a "third pandemic wave" and explored whether vaccinating the population at different rates and times would mitigate the wave. This model included explicit representations of the region's individuals, school systems, workplaces/commutes, households, and communities.Results: Three mechanisms were identified that could cause a third pandemic wave; substantially increased viral transmissibility from seasonal forcing (changing influenza transmission with changing environmental conditions, i.e., seasons) and progressive viral adaptation; an immune escape variant; and changes in social mixing from holiday school closures. Implementing vaccination for these mechanisms, even during the down-slope of the fall epidemic wave, significantly mitigated the third wave. Scenarios showed the gains from initiating vaccination earlier, increasing the speed of vaccination, and prioritizing population subgroups based on Advisory Committee on Immunization Practices recommendations.Conclusions: Additional waves in an epidemic can be mitigated by vaccination even when an epidemic appears to be waning. [ABSTRACT FROM AUTHOR]

Background: The Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP's preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults., Methods: We used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18-64 years old. Model inputs included 2018-2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019-2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season., Results: Among adults ages 18-64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50-64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18-64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18-64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50-64-year-olds., Conclusions: While RIV4 was effective and cost-effective relative to SD-IIV4 for both 50-64-year-old and 18-64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18-64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50-64 year olds) to maximize their cost-benefit ratios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jonathan M Raviotta reports financial support was provided by Sanofi Pasteur Inc. Richard K Zimmerman reports a relationship with Sanofi Pasteur Inc that includes: funding grants. Mary Patricia Nowalk reports a relationship with Sanofi Pasteur Inc that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Multiple factors, such as less complex U.S. adult pneumococcal recommendations that could increase vaccination rates, childhood pneumococcal vaccination indirect effects that decrease adult vaccination impact, and increased vaccine hesitancy (particularly in underserved minorities), could diminish the cost-effectiveness of programs to increase pneumococcal vaccination in older adults. Prior analyses supported the economic favorability of these programs., Methods: A Markov model compared no vaccination and current recommendations (either 20-valent pneumococcal conjugate vaccine [PCV20] alone or 15-valent pneumococcal conjugate vaccine plus the 23-valent pneumococcal polysaccharide vaccine [PCV15/PPSV23]) without or with programs to increase vaccine uptake in Black and non-Black 65-year-old cohorts. Pre-pandemic population- and serotype-specific pneumococcal disease risk and illness/vaccine costs came from U.S., Databases: Program costs were $2.19 per vaccine-eligible person and increased absolute vaccination likelihood by 7.5%. Delphi panel estimates and trial data informed vaccine effectiveness values. Analyses took a healthcare perspective, discounting at 3%/year over a lifetime time horizon., Results: Uptake programs decreased pneumococcal disease overall. In Black cohorts, PCV20 without program cost $216,805 per quality-adjusted life year (QALY) gained compared with no vaccination; incremental cost-effectiveness was $245,546/QALY for PCV20 with program and $425,264/QALY for PCV15/PPSV23 with program. In non-Black cohorts, all strategies cost >$200,000/QALY gained. When considering the potential indirect effects from childhood vaccination, all strategies became less economically attractive. Increased vaccination with less complex strategies had negligible effects. In probabilistic sensitivity analyses, current recommendations with or without programs were unlikely to be favored at thresholds <$200,000/QALY gained., Conclusion: Current U.S. pneumococcal vaccination recommendations for older adults were unlikely to be economically reasonable with or without programs to increase vaccine uptake. Alternatives to current pneumococcal vaccines that include pneumococcal serotypes associated with adult disease should be considered., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study., Methods: From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 - adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure., Results: Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories., Conclusions: During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19., Competing Interests: Potential conflicts of interest. R. K. Z. reports grants from the CDC during the conduct of the study and grants from Sanofi Pasteur outside the submitted work. C. G. G. reports other from the CDC, grants from the National Institutes of Health, other from the Food and Drug Administration, grants and other from the Agency for Healthcare Research and Quality, other from Merck, and other from Syneos Health, outside the submitted work. H. K. T. reports grants from the CDC during the conduct of the study. E. A. B. reports grants from the CDC during the conduct of the study. E. T. M. reports grants from the CDC during the conduct of the study and grants from Merck outside the submitted work. M. G. reports grants from the CDC during the conduct of the study and grants from the CDC, CDC-Vanderbilt, and CDC–Abt Associates, outside the submitted work. M. G. is also cochair of the Infectious Diseases and Immunization Committee, Texas Pediatric Society, Texas Chapter of the American Academy of Pediatrics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objectives: This study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds., Methods: A Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty., Results: In Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold., Conclusions: When considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine., Methods: In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted., Results: Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert., Conclusions: These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness., Competing Interests: Potential conflicts of interest . All authors: The authors have ongoing relationships with the NIH and CDC as stated in the financial support section. The authors have a previous funding relationship with Sanofi Pasteur Inc., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses. From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wateska has had a research grant from NIAID in the past 3 years. Dr. Nowalk has had research grants from Merck & Co., Inc. and Sanofi Pasteur. in the past 3 years. Dr. Schaffner has had a research grant from CDC in the past 3 years. Dr. Zimmerman has had research grants from NIH and Sanofi Pasteur. in 3 years. Dr. Smith has had research grants from NIAID and Sanofi Pasteur. in the past 3 years. Other authors have no competing interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the United States, annual influenza vaccination is recommended for all persons aged ≥6 months. Using data from four vaccine effectiveness (VE) networks during the 2023-24 influenza season, interim influenza VE was estimated among patients aged ≥6 months with acute respiratory illness-associated medical encounters using a test-negative case-control study design. Among children and adolescents aged 6 months-17 years, VE against influenza-associated outpatient visits ranged from 59% to 67% and against influenza-associated hospitalization ranged from 52% to 61%. Among adults aged ≥18 years, VE against influenza-associated outpatient visits ranged from 33% to 49% and against hospitalization from 41% to 44%. VE against influenza A ranged from 46% to 59% for children and adolescents and from 27% to 46% for adults across settings. VE against influenza B ranged from 64% to 89% for pediatric patients in outpatient settings and from 60% to 78% for all adults across settings. These findings demonstrate that the 2023-24 seasonal influenza vaccine is effective at reducing the risk for medically attended influenza virus infection. CDC recommends that all persons aged ≥6 months who have not yet been vaccinated this season get vaccinated while influenza circulates locally., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Emmanuel B. Walter reports institutional support from Pfizer, Moderna, Seqiris, Clinetic, and Najit Technologies Inc., consulting fees from ILiAD Biotechnologies, payment from the College of Diplomates of the American Board of Pediatric Dentistry, travel support from the American Academy of Pediatrics, and paid compensation for participation on the Vaxcyte Scientific Advisory Board. Yuwei Zhu reports participation on a Vanderbilt University Medical Center Data Safety Monitoring Board. Sara Y. Tartof reports institutional support from Pfizer and Genentech. Samantha M. Olson reports travel support from the Gates Foundation. Nicola P. Klein reports institutional support from Sanofi Pasteur, Merck, Pfizer, Seqirus, and GlaxoSmithKline; membership on an expert panel for a planned hepatitis E Phase II vaccine clinical trial among pregnant women in Pakistan; membership in Western States COVID-19 Scientific Safety Review Workgroup, Board on Population Health and Public Health Practice, National Academies of Science, Engineering and Medicine, and National Vaccine Advisory Committee Safety Subcommittee. Manjusha Gaglani reports receipt of honorarium for educational webinar presentation on respiratory viruses from the Texas Pediatric Society, Texas Chapter of the American Academy of Pediatrics, and serving as co-chair of the Infectious Diseases and Immunization Committee and Chair of the Texas Respiratory Syncytial Virus Taskforce, Texas Pediatric Society. Kevin W. Gibbs reports grants or contracts from the Department of Defense and the National Institutes of Health (NIH) and service as chair of the Vanderbilt University Medical Center Data Safety Monitoring Board. Adit A. Ginde reports institutional support from the NIH, the Department of Defense, AbbVie, and Faron Pharmaceuticals, consulting fees (paid to institution) from Biomeme and Seastar, and participation on data safety monitoring boards for the NIH and Emory University. Richard K. Zimmerman reports institutional support from the NIH and Sanofi Pasteur, and honorarium from Clinical Educational Alliance. Mary A. Staat reports institutional support from NIH, Pfizer, and Merck and royalties for Up-to-Date chapter on International Adoption. Stacey House reports institutional support from Seegene, Inc., Abbot, Healgen, Roche, CorDx, Hologic, Cepheid, Janssen, and Wondfo Biotech. Geoffrey A. Weinberg reports institutional support from the New York State Department of Health AIDS Institute, consulting fees from Inhalon Biopharma for participation on a Scientific Advisory Board, and honoraria from Merck & Company for textbook chapters. Marian G. Michaels reports institutional support from the National Institute on Allergy and Infectious Diseases and complimentary meeting attendance for presentation at the American Transplant Congress on respiratory viruses. Emily T. Martin reports receipt of grants or contracts from Merck. Natasha B. Halasa reports receipt of grants from Sanofi, Quidell, and Merck. Elie A. Saade reports institutional support from Protein Sciences Corporation, consulting fees, honoraria, and travel support from Johnson & Johnson and participation on a Johnson & Johnson Data Safety Monitoring Board. No other potential conflicts of interest were disclosed.

Objective: This study aimed to estimate the societal cost of racial disparities in pneumococcal disease among US adults aged ≥  50 years., Methods: In a model-based analysis, societal costs of invasive pneumococcal disease (IPD) and hospitalized nonbacteremic pneumococcal pneumonia (NBP) were estimated using (1) direct medical costs plus indirect costs of acute illness; (2) indirect costs of pneumococcal mortality; and (3) direct and indirect costs of related disability. Disparities costs were calculated as differences in average per-person pneumococcal disease cost between Black and non-Black adults aged ≥  50 years multiplied by the Black population aged ≥  50 years. Costs were in 2019 US dollars (US$), with future costs discounted at 3% per year., Results: Total direct and indirect costs per IPD case were US$186,791 in Black populations and US$182,689 in non-Black populations; total hospitalized NBP costs per case were US$100,632 (Black) and US$96,781 (non-Black). The difference in population per-person total pneumococcal disease costs between Black and non-Black adults was US$47.85. Combined societal costs of disparities for IPD and hospitalized NBP totaled US$673.2 million for Black adults aged ≥  50 years. Disease and disability risks, life expectancy, and case-fatality rates were influential in one-way sensitivity analyses, but the lowest cost across all analyses was US$194 million. The 95% probability range of racial disparity costs were US$227.2-US$1156.9 million in a probabilistic sensitivity analysis., Conclusions: US societal cost of racial pneumococcal disease disparities in persons aged ≥ 50 years is substantial. Successful pneumococcal vaccination policy and programmatic interventions to mitigate these disparities could decrease costs and improve health., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Newer influenza vaccine formulations have entered the market, but real-world effectiveness studies are not widely conducted until there is sufficient uptake. We conducted a retrospective test-negative case-control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine or RIV4, compared with standard dose vaccines (SD) in a health system with significant RIV4 uptake. Using the electronic medical record (EMR) and the Pennsylvania state immunization registry to confirm influenza vaccination, VE against outpatient medically attended visits was calculated. Immunocompetent outpatients ages 18-64 years seen in hospital-based clinics or emergency departments who were tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays during the 2018-2019 and 2019-2020 influenza seasons were included. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE. Among this mostly white and female cohort of 5,515 individuals, 510 were vaccinated with RIV4 and 557 were vaccinated with SD, with the balance of 4,448 (81%) being unvaccinated. Adjusted influenza VE estimates were 37% overall (95% CI = 27, 46), 40% (95% CI = 25, 51) for RIV4 and 35% (95% CI = 20, 47) for standard dose vaccines. Overall, rVE of RIV4 compared to SD was not significantly higher (11%; 95% CI = -20, 33). Influenza vaccines were moderately protective against medically attended outpatient influenza during the 2018-2019 and 2019-2020 seasons. Although the point estimates are higher for RIV4, the large confidence intervals around VE estimates suggest this study was underpowered to detect significant rVE of individual vaccine formulations.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

Background: Relative effectiveness of various vaccine formulations provide important input for vaccine policy decisions and provider purchasing decisions. We used electronic databases to conduct a test-negative case control study to determine relative vaccine effectiveness (rVE) of recombinant influenza vaccine (RIV4) compared with standard dose vaccines (SD-IIV4) against influenza hospitalization., Methods: Adults 18-64 and ≥65 years of age hospitalized in a large U.S. health system (19 hospitals) in 2018-2019 and 2019-2020 who were clinically tested for influenza using reverse transcription polymerase chain reaction (RT-PCR) assays were included. The hospital system electronic medical record (EMR) and the state immunization registry were used to confirm influenza vaccination. Propensity scores with inverse probability weighting were used to adjust for potential confounders and determine rVE., Results: Of the 14,590 individuals included in the primary analysis, 3,338 were vaccinated with RIV4 and 976 were vaccinated with SD-IIV4, with the balance of 10,276 being unvaccinated. Most participants were white (80 %), most (70 %) had a high-risk condition, just over half were female (54 %) and age 65 years or older (53 %). Overall RIV4 rVE was significant when adjusted for propensity scores with inverse probability weights (rVE = 31; 95 % CI = 11 %, 46 %). Among younger adults (18-64 years-old), overall rVE of RIV4 was significant (rVE = 29; 95 % CI = 4 %, 47 %)., Conclusions: Over all adults, both RIV4 and SD-IIV4 were effective against influenza hospitalization, with RIV4 providing better protection compared with SD-IIV4 overall, for females, younger adults, and those with no high-risk conditions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Zimmerman, Raviotta, Nowalk, and Balasubramani received investigator-initiated grant funding from Sanofi for this project. Drs. Nowalk and Balasubramani, have grant funding from Merck & Co., Inc. for an unrelated project. Ms. Dauer and Mr. Clarke have no conflicts to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: CDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear., Methods: A Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined., Results: In the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios., Conclusion: An in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Smith and Zimmerman have an active research grant from Sanofi Pasteur on unrelated topics. Dr. Nowalk has grant funding from Merck & Co., Inc. on an unrelated topic and had research grants within 3 years from Pfizer, Inc. and Sanofi Pasteur on unrelated topics that are no longer active. Dr. Schaffner is a member of a data safety monitoring board (DSMB) for Pfizer, former member of a DSMB for Merck, and has served as a consultant to Roche Diagnostics. Dr. Harrison has served as a consultant to GSK, Merck, Pfizer, and Sanofi Pasteur. All other authors have no competing interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology., Methods: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination., Results: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response., Conclusions: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response., Clinical Trials No: NCT03982069., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network., Methods: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016-2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes., Results: Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P < .0001; COPD: 47.6% vs 35.8%, P < .0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06-1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09-1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI, .82-1.28 and OR, 1.17; 95% CI, .91-1.49, respectively)., Conclusions: The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI., Competing Interests: Potential conflicts of interest. L. E. L. reports grant support paid to institution from the CDC and funding from Janssen Scientific Affairs paid to institution. E. T. M. reports institutional grant support from the CDC, CDC-Abt Associates, and Merck and grants or contracts unrelated to this work from the NIH, Merck, and FluLab. A. N. M reports a role as member of the Society of Healthcare Epidemiology of America Board of Trustees. F. P. S. reports a research grant paid to institution and unrelated to this work from Ansun and payment to author for honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Janssen. M. J. G. reports institutional grant support or contracts from the CDC; funding from the CDC, CDC-Abt Associates, MedImmune, Janssen, and Pfizer; and a role as co-chair of the Infectious Diseases and Immunization Committee and as chair of the Texas RSV Taskforce for the Texas Pediatric Society, Texas Chapter of American Academy of Pediatrics. A. S. L. reports grants or contracts unrelated to this work from the CDC, Burroughs Wellcome Fund, and National Institute of Allergy and Infectious Diseases (NIAID) and consulting fees from Sanofi and from Roche as a paid member of the baloxavir trial steering committee. R. K. Z. reports a research grant to their university from Sanofi Pasteur. D. B. M. reports consulting fees (advisory group payment to author) from Moderna, Seqirus, Sanofi Pasteur, Novavax, and Valneva and lecture payment to author from Merck and Pfizer. 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI)., Methods: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status., Results: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated., Conclusions: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Current influenza vaccines have limited effectiveness. COVID-19 vaccines using mRNA technology have demonstrated very high efficacy, suggesting that mRNA vaccines could be more effective for influenza. Several such influenza vaccines are in development. FRED, an agent-based modeling platform, was used to estimate the impact of more effective influenza vaccines on seasonal influenza burden., Methods: Simulations were performed using an agent-based model of influenza that included varying levels of vaccination efficacy (40-95 % effective). In some simulations, level of infectiousness and/or length of infectious period in agents with breakthrough infections was also decreased. Impact of increased and decreased levels of vaccine uptake were also modeled. Outcomes included number of symptomatic influenza cases estimated for the US., Results: Highly effective vaccines significantly reduced estimated influenza cases in the model. When vaccine efficacy was increased from 40 % to a maximum of 95 %, estimated influenza cases in the US decreased by 43 % to > 99 %. The base simulation (40 % efficacy) resulted in ∼ 28 million total yearly cases in the US, while the most effective vaccine modeled (95 % efficacy) decreased estimated cases to ∼ 22,000., Discussion: Highly effective vaccines could dramatically reduce influenza burden. Model estimates suggest that even modest increases in vaccine efficacy could dramatically reduce seasonal influenza disease burden., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mary G Krauland reports financial support was provided by Centers for Disease Control and Prevention. Richard K Zimmerman reports a relationship with Sanofi Pasteur that includes: funding grants. Jonathan M Raviotta reports a relationship with Sanofi Pasteur that includes: funding grants. John V. Williams reports a relationship with Quidel Corp that includes: board membership. John V. Williams reports a relationship with GlaxoSmithKline that includes: consulting or advisory., (© 2022 The Author(s).)

Background: The ongoing circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a diagnostic challenge because symptoms of coronavirus disease 2019 (COVID-19) are difficult to distinguish from other respiratory diseases. Our goal was to use statistical analyses and machine learning to identify biomarkers that distinguish patients with COVID-19 from patients with influenza., Methods: Cytokine levels were analyzed in plasma and serum samples from patients with influenza and COVID-19, which were collected as part of the Centers for Disease Control and Prevention's Hospitalized Adult Influenza Vaccine Effectiveness Network (inpatient network) and the US Flu Vaccine Effectiveness (outpatient network)., Results: We determined that interleukin (IL)-10 family cytokines are significantly different between COVID-19 and influenza patients. The results suggest that the IL-10 family cytokines are a potential diagnostic biomarker to distinguish COVID-19 and influenza infection, especially for inpatients. We also demonstrate that cytokine combinations, consisting of up to 3 cytokines, can distinguish SARS-CoV-2 and influenza infection with high accuracy in both inpatient (area under the receiver operating characteristics curve [AUC] = 0.84) and outpatient (AUC = 0.81) groups, revealing another potential screening tool for SARS-CoV-2 infection., Conclusions: This study not only reveals prospective screening tools for COVID-19 infections that are independent of polymerase chain reaction testing or clinical condition, but it also emphasizes potential pathways involved in disease pathogenesis that act as potential targets for future mechanistic studies., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Persons with COVID-19-like illnesses are advised to stay home to reduce the spread of SARS-CoV-2. We assessed relationships between telework experience and COVID-19 illness with work attendance when ill. Adults experiencing fever, cough, or loss of taste or smell who sought healthcare or COVID-19 testing in the United States during March-November 2020 were enrolled. Adults with telework experience before illness were more likely to work at all (onsite or remotely) during illness (87.8%) than those with no telework experience (49.9%) (adjusted odds ratio 5.48, 95% CI 3.40-8.83). COVID-19 case-patients were less likely to work onsite (22.1%) than were persons with other acute respiratory illnesses (37.3%) (adjusted odds ratio 0.36, 95% CI 0.24-0.53). Among COVID-19 case-patients with telework experience, only 6.5% worked onsite during illness. Telework experience before illness gave mildly ill workers the option to work and improved compliance with public health recommendations to stay home during illness.

Background: Little is known about the effects of a mild SARS-CoV-2 infection on health-related quality of life., Methods: This prospective observational study of symptomatic adults (18-87 years) who sought outpatient care for an acute respiratory illness, was conducted from 3/30/2020 to 4/30/2021. Participants completed the Short Form Health Survey (SF-12) at enrollment and 6-8 weeks later, to report their physical and mental health function levels as measured by the physical health and mental health composite scores (PHC and MHC, respectively). PHC and MHC scores for COVID-19 cases and non-COVID cases were compared using t-tests. Multivariable regression modeling was used to determine predictors of physical and mental health function at follow-up., Results: Of 2301 enrollees, 426 COVID-19 cases and 547 non-COVID cases completed both surveys. PHC improved significantly from enrollment to follow-up for both COVID-19 cases (5.4 ± 0.41; P  < 0.001) and non-COVID cases (3.3 ± 0.32; P  < 0.001); whereas MHC improved significantly for COVID-19 cases (1.4 ± 0.51; P  < 0.001) and decreased significantly for non-COVID cases (-0.8 ± 0.37; P < 0.05). Adjusting for enrollment PHC, the most important predictors of PHC at follow-up included male sex (β = 1.17; SE = 0.5; P  = 0.021), having COVID-19 (β = 1.99; SE = 0.54; P  < 0.001); and non-white race (β = -2.01; SE = 0.70; P  = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (β = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (β = 2.42; SE = 0.67; P  < 0.001)., Conclusion: Both COVID-19 cases and non-COVID cases reported improved physical health function at 6-8 weeks' convalescence; whereas mental health function improved among COVID-19 cases but declined among non-COVID cases. Both physical and mental health functioning were significantly better among males with COVID-19 than females., Competing Interests: Drs. Nowalk and Balasubramani have grant funding from 10.13039/100004334Merck & Co., Inc. for an unrelated project. Drs. Zimmerman, Nowalk and Balasubramani have grant funding from 10.13039/100014588Sanofi on an unrelated project. Mr. Clarke, Ms. Clarke, Mr. Susick, Ms. Dauer, Ms. Sax, Dr. Taylor, Dr. Moehling Geffel have no conflicts to report., (© 2023 The Authors.)

Background: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults., Methods: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen., Results: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1)., Conclusion: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed., Competing Interests: Declaration of Competing Interest RKZ has received unrelated funding by Sanofi.  MPN has research funding from Merck & Co., Inc. and Sanofi Pasteur for unrelated studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) is becoming increasingly recognized as a serious threat to vulnerable population subgroups. This study describes the statistical analysis plan for a retrospective cohort study of adults hospitalized for acute respiratory infection (ARI) to estimate the population burden of RSV especially for groups such as the elderly, pregnant women and solid organ transplant patients. Disease burden estimates are essential for setting vaccine policy, e.g., should RSV vaccine become available, burden estimates may inform recommendations to prioritize certain high-risk groups. The study population is residents of Allegheny County, Pennsylvania ≥18 years of age who were hospitalized in Pennsylvania during the period September 1, 2015-August 31, 2018. Data sources will include U.S. Census, Pennsylvania Health Care Cost Containment Council (PHC4) and the electronic medical record for the health system to which the hospitals belong. The algorithm involves: 1) ARI-associated hospitalizations in PHC4 data; 2) adjustment for ARI hospitalizations among county residents but admitted to hospitals outside the county; and 3) RSV detections from respiratory viral panels. Key sensitivity analyses will adjust for undertesting for viruses in the fall and spring quarters. The results will be population-based estimates, stratified by age and risk groups. Adjusting hospitalization data using a multiplier method is a simple means to estimate the impact of RSV in a given area. This algorithm can be applied to other health systems and localities to estimate RSV and other respiratory pathogen burden in adults, to estimate burden following introduction of RSV vaccine and to make cost-effectiveness estimates.

Background: The 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recently recommended for US adults, giving either PCV20 alone or PCV15 followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) to all 65 + -year-olds and to high-risk younger adults. However, general population recommendations to vaccinate all 50-year-olds could reduce racial pneumococcal disease disparities given greater risk in underserved minority populations., Methods: A Markov model examining hypothetical 50-year-old Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts estimated the incremental cost effectiveness of US adult pneumococcal vaccination recommendations compared to PCV20 or PCV15/PPSV23 for all 50-year-olds with no vaccination thereafter, or PCV20 or PCV15/PPSV23 for all at ages 50 and 65 years (50/65). Model parameters came from US databases, clinical trials, and Delphi panels. Cohorts were followed over their lifetimes from a healthcare perspective discounted at 3 %/year., Results: PCV15/PPSV23 given at ages 50/65 had greatest public health impact. In Black cohorts, PCV15/PPSV23 at age 50 cost $104,723/quality adjusted life year (QALY) gained compared to PCV20 at age 50, while PCV15/PPSV23 at 50/65 cost $240,952/QALY gained compared to PCV15/PPSV23 at age 50. Both current recommendation options were more expensive and less effective than other strategies in both cohorts. In sensitivity analyses, age-based PCV20 or PCV15/PPSV23 use at ages 50 or 50/65 could be favorable depending on vaccine effectiveness or differential vaccine uptake, while current recommendations remained unfavorable., Conclusion: Recent risk-based US adult pneumococcal vaccination recommendations for adults < 65-years-old, were economically and clinically unfavorable compared to general population vaccination of all 50-year-olds in Black and non-Black cohorts. An age-based pneumococcal vaccination recommendation at age 50 years may reduce inequities in pneumococcal disease burden., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We sought to evaluate the trends of HPV vaccination between 03/2019-09/2021 and whether the impact of the COVID pandemic on HPV vaccination varied by race/ethnicity and neighborhood deprivation index (NDI)., Methods: Electronic medical records at Kaiser Permanente Southern California were used to assess monthly volume of HPV vaccine doses administered among children aged 9-12.9yrs, and up-to-date coverage (% vaccinated) by age 13 between 03/2019-09/2021. Modified Poisson models were used to evaluate the interactions between race/ethnicity, NDI and the pandemic periods on HPV vaccine coverage., Results: HPV vaccine doses administered in 2020/2021 have returned to the 2019 level after the initial drop. The average up-to-date coverage in 05/2021-09/2021 (54.8%) remained lower than the pre-pandemic level (58.5%). The associations between race/ethnicity, NDI and HPV vaccine coverage did not vary due to the pandemic., Conclusion: HPV vaccine promotion efforts are needed to address COVID-19 pandemic's lasting impact on HPV vaccination coverage., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chao CR received research funding from Merck for an unrelated project., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Acute respiratory infections (ARIs) result in millions of illnesses and hundreds of thousands of hospitalizations annually in the United States. The responsible viruses include influenza, parainfluenza, human metapneumovirus, coronaviruses, respiratory syncytial virus (RSV), and human rhinoviruses. This study estimated the population-based hospitalization burden of those respiratory viruses (RVs) over 4 years, from July 1, 2015 to June 30, 2019, among adults ≥18 years of age for Allegheny County (Pittsburgh), Pennsylvania., Methods: We used population-based statewide hospital discharge data, health system electronic medical record (EMR) data for RV tests, census data, and a published method to calculate burden., Results: Among 26,211 eligible RV tests, 67.6% were negative for any virus. The viruses detected were rhinovirus/enterovirus (2552; 30.1%), influenza A (2,299; 27.1%), RSV (1082; 12.7%), human metapneumovirus (832; 9.8%), parainfluenza (601; 7.1%), influenza B (565; 6.7%), non-SARS-CoV-2 coronavirus (420; 4.9% 1.5 years of data available), and adenovirus (136; 1.6%). Most tests were among female (58%) and White (71%) patients with 60% of patients ≥65 years, 24% 50-64 years, and 16% 18-49 years. The annual burden ranged from 137-174/100,000 population for rhinovirus/enterovirus; 99-182/100,000 for influenza A; and 56-81/100,000 for RSV. Among adults &lt;65 years, rhinovirus/enterovirus hospitalization burden was higher than influenza A; whereas the reverse was true for adults ≥65 years. RV hospitalization burden increased with increasing age., Conclusions: These virus-specific ARI population-based hospital burden estimates showed significant non-influenza burden. These estimates can serve as the basis for several areas of research that are essential for setting funding priorities and guiding public health policy., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)