Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older.

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.

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis.

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.

Societal Cost of Racial Pneumococcal Disease Disparities in US Adults Aged 50 Years or Older.

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.

Work Attendance with Acute Respiratory Illness Before and During COVID-19 Pandemic, United States, 2018-2022.

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.

Differential Induction of Interferon Stimulated Genes by Cell-based Versus Egg-based Quadrivalent Influenza Vaccines in Children During the 2018-19 Season.

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. Here, we examine peripheral immune activation following egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated and RNA sequenced from 81 study participants (41 Fluzone, egg-based and 40 Flucelvax, cell based) pre- and 7 days post- vaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted. 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. 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.

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults.

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.

A Randomized Controlled Trial to Compare Immunogenicity to Cell-Based Versus Live-Attenuated Influenza Vaccines in Children.

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.

Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018-2019 and 2019-2020 calculated using a retrospective test-negative design.

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.

Relationship between Telework Experience and Presenteeism during COVID-19 Pandemic, United States, March-November 2020.

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.

Effect of mild COVID-19 on health-related quality of life.

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 (ß = 1.17; SE = 0.5; P = 0.021), having COVID-19 (ß = 1.99; SE = 0.54; P < 0.001); and non-white race (ß = -2.01; SE = 0.70; P = 0.004). Adjusting for enrollment MHC, the most important predictors of MHC at follow-up included male sex (ß = 1.92; SE = 0.63; P = 0.002) and having COVID-19 (ß = 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.

Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season.

BACKGROUND: In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. METHODS: Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. RESULTS: Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2-positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%-49%) overall. CONCLUSIONS: Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons.

Population-based hospitalization burden estimates for respiratory viruses, 2015-2019.

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 <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.

Cost-Effectiveness of Newly Recommended Pneumococcal Vaccination Strategies in Older Underserved Minority Adults in the USA.

INTRODUCTION: US pneumococcal vaccination recommendations for adults aged 65 years or older recently changed, with options for either 20-valent pneumococcal conjugate vaccine (PCV20) or the combination of 15-valent conjugate vaccine (PCV15) followed by 23-valent polysaccharide vaccine (PPSV23) 1 year later. Underserved minority adults are at higher risk for pneumococcal disease. METHODS: A Markov decision analysis model estimated the incremental cost-effectiveness of the newly adopted general population pneumococcal vaccination strategies in older underserved minority adults. The model examined hypothetical 65-year-old US Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts receiving PCV20 or PCV15/PPSV23, or no vaccination. Main outcome measures included incremental cost-effectiveness per quality-adjusted life year (QALY) gained and pneumococcal disease public health outcomes. RESULTS: Black cohorts had a greater risk of pneumococcal disease hospitalization compared to non-Black cohorts. In Black cohorts, total per person PCV20 strategy costs, compared to no vaccination, were $124 higher while gaining 0.00073 QALY, or $169,540/QALY gained. PCV15/PPSV23 cost $535,797/QALY compared to PCV20. In the non-Black cohort, PCV20 cost $210,529/QALY gained compared to no vaccination and PCV15/PPSV23 cost $728,423/QALY. Plausible variation of vaccine effectiveness minimally affected PCV20 strategy results and made PCV15/PPSV23 more unfavorable. In scenarios where the simpler one-vaccine PCV20 strategy increased absolute vaccine uptake by 10%, PCV20 cost-effectiveness changed minimally while PCV15/PPSV23 cost in excess of $6 million/QALY in the Black cohort. In probabilistic sensitivity analyses that varied all parameters simultaneously, PCV15/PPSV23 was unlikely to be favored at thresholds less than $500,000/QALY gained. CONCLUSION: General population recommendations for PCV20 use are substantially more economically reasonable in Black and non-Black older adult populations than PCV15/PPSV23. If using a single vaccine increases uptake, which is potentially more likely in the underserved, then PCV20 use becomes even more favorable.

Estimating the burden of adult hospitalized RSV infection including special populations.

BACKGROUND: Numerous studies in the U.S. have made estimates of the RSV burden among adults that vary widely due to differences in methodology, reliance on influenza surveillance, which does not adequately capture all RSV clinical symptoms, and lack of diagnostic methods to identify RSV when viral loads are low. Nevertheless, accurate burden estimates can inform healthcare planning, resource allocation and potentially, RSV vaccine policy. METHODS: A simple method combined with statewide and local hospitalization, medical record and U.S. Census data were used to estimate population-based RSV hospitalization burden among adults ages 18-64 years, ≥65 years, and including immunocompetent, immunocompromised and pregnant individuals during 2015-2018 for Allegheny County, Pennsylvania. Economic burden of hospitalization was estimated using state-provided average hospitalization charges for comparisons across patient groups. RESULTS: The largest burden was borne by adults ≥ 65 years of age whose rates per 100,000 population of that age group (939/100,000) were 7.0-9.0 times those of adults 18-64 years of age (118/100,000). Immunosuppressed patients bore the greatest relative burden of RSV hospitalizations (1,288-1,562/100,000 immunosuppressed individuals). RSV burden ranged from 0 to 808/100,000 pregnant women. Average total charges for RSV hospitalization in Allegheny County across all adults increased from $39 million in 2015-2016 to $57 million in 2016-2017 to $89 million in 2017-2018, due to both increased average charges for an acute respiratory hospitalization and increased numbers of RSV cases. CONCLUSIONS: These RSV burden estimates add to the body of knowledge to guide public health policy makers and offer a method for simply and easily producing population-based burden estimates.

Vaccine-associated attenuation of subjective severity among outpatients with influenza.

Influenza vaccines can mitigate illness severity, including reduced risk of ICU admission and death, in people with breakthrough infection. Less is known about vaccine attenuation of mild/moderate influenza illness. We compared subjective severity scores in vaccinated and unvaccinated persons with medically attended illness and laboratory-confirmed influenza. Participants were prospectively recruited when presenting for care at five US sites over nine seasons. Participants aged ≥ 16 years completed the EQ-5D-5L visual analog scale (VAS) at enrollment. After controlling for potential confounders in a multivariable model, including age and general health status, VAS scores were significantly higher among 2,830 vaccinated participants compared with 3,459 unvaccinated participants, indicating vaccinated participants felt better at the time of presentation for care. No differences in VAS scores were observed by the type of vaccine received among persons aged ≥ 65 years. Our findings suggest vaccine-associated attenuation of milder influenza illness is possible.

Estimating the burden of adult hospitalized RSV infection using local and state data - methodology.

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.

Interim Estimates of 2021-22 Seasonal Influenza Vaccine Effectiveness - United States, February 2022.

In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months except when contraindicated (1). Currently available influenza vaccines are designed to protect against four influenza viruses: A(H1N1)pdm09 (the 2009 pandemic virus), A(H3N2), B/Victoria lineage, and B/Yamagata lineage. Most influenza viruses detected this season have been A(H3N2) (2). With the exception of the 2020-21 season, when data were insufficient to generate an estimate, CDC has estimated the effectiveness of seasonal influenza vaccine at preventing laboratory-confirmed, mild/moderate (outpatient) medically attended acute respiratory infection (ARI) each season since 2004-05. This interim report uses data from 3,636 children and adults with ARI enrolled in the U.S. Influenza Vaccine Effectiveness Network during October 4, 2021-February 12, 2022. Overall, vaccine effectiveness (VE) against medically attended outpatient ARI associated with influenza A(H3N2) virus was 16% (95% CI = -16% to 39%), which is considered not statistically significant. This analysis indicates that influenza vaccination did not reduce the risk for outpatient medically attended illness with influenza A(H3N2) viruses that predominated so far this season. Enrollment was insufficient to generate reliable VE estimates by age group or by type of influenza vaccine product (1). CDC recommends influenza antiviral medications as an adjunct to vaccination; the potential public health benefit of antiviral medications is magnified in the context of reduced influenza VE. CDC routinely recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months as long as influenza viruses are circulating, even when VE against one virus is reduced, because vaccine can prevent serious outcomes (e.g., hospitalization, intensive care unit (ICU) admission, or death) that are associated with influenza A(H3N2) virus infection and might protect against other influenza viruses that could circulate later in the season.

Vaccine effectiveness against COVID-19 among symptomatic persons aged ≥12 years with reported contact with COVID-19 cases, February-September 2021.

BACKGROUND: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood. METHODS: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression. RESULTS: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2). CONCLUSIONS: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage.

Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.

Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose.