Substantial health and economic burden of COVID-19 during the year after acute illness among US adults at high risk of severe COVID-19.

BACKGROUND: Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19. METHODS: Eligible adults were diagnosed with COVID-19 from April 1 to May 31, 2020, had ≥ 1 condition placing them at risk of severe COVID-19, and were enrolled in Optum's de-identified Clinformatics® Data Mart Database for ≥ 12 months before and ≥ 13 months after COVID-19 diagnosis. Percentages of diagnoses, medications, resource use, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified by age and COVID-19 severity. RESULTS: The cohort included 19,558 patients (aged 18-64 y, n = 9381; aged ≥ 65 y, n = 10,177). Compared with baseline, patients during the post-acute phase had increased percentages of blood disorders (16.3%), nervous system disorders (11.1%), and mental and behavioral disorders (7.7%), along with increases in related prescriptions. Overall, there were substantial increases in inpatient and outpatient healthcare utilization, along with a 23.0% increase in medical costs. Changes were greatest among older patients and those admitted to the intensive care unit for acute COVID-19 but were also observed in younger patients and those who did not require COVID-19 hospitalization. CONCLUSIONS: There is a significant clinical and economic burden of post-COVID conditions among US individuals at high risk for severe COVID-19.

Effectiveness of BNT162b2 BA.4/5 Bivalent COVID-19 Vaccine against Long COVID Symptoms: A US Nationwide Study.

BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

Economic burden of COVID-19 for employers and employees in the United States.

OBJECTIVE: Describe the economic burden of COVID-19 on employers and employees in the United States (US). METHODS: A targeted literature review was conducted to evaluate the impact of COVID-19 on US-based employers and employees in terms of healthcare resource utilization (HCRU), medical costs, and costs associated with work-loss. Searches were conducted in MEDLINE, Embase, and EconLit using a combination of disease terms, populations, and outcomes to identify articles published from January 2021 to November 4, 2022. As data from the employer perspective were lacking, additional literature related to influenza were included to contextualize the impact of COVID-19, as it shifts into an endemic state, within the existing respiratory illness landscape. RESULTS: A total of 41 articles were included in the literature review. Employer and employee perspectives were not well represented in the literature, and very few articles overlapped on any given outcome. HCRU, costs, and work impairment vary by community transmission levels, industry type, population demographics, telework ability, mitigation implementation measures, and company policies. Work-loss among COVID-19 cases were higher among the unvaccinated and in the week following diagnosis and for some, these continued for 6 months. HCRU is increased in those with COVID-19 and COVID-19-related HCRU can also continue for 6 months. CONCLUSIONS: COVID-19 continues to be a considerable burden to employers. The majority of COVID-19 cases impact working age adults. HCRU is mainly driven by outpatient visits, while direct costs are driven by hospitalization. Productivity loss is higher for unvaccinated individuals. An increased focus to support mitigation measures may minimize hospitalizations and work-loss. A data-driven approach to implementation of workplace policies, targeted communications, and access to timely and appropriate therapies for prevention and treatment may reduce health-related work-loss and associated cost burden.

In January 2020, the US government declared COVID-19 a public health emergency. This lasted until May 2023. To fight this health emergency, the US government provided free testing, vaccination, and treatment. Although the US government has declared the emergency over, COVID-19 continues to infect people. For people with private health insurance, costs associated with COVID-19 patient healthcare have now been transferred from the government to employers. In this study, we collected information from published scientific articles about the costs of COVID-19 for employers and workers in the US. We found that people who were not vaccinated against COVID-19 required more medical care and cost more than people who were vaccinated. In some cases, this trend lasted for as long as 6 months. This was mostly because of workers missing work, not working effectively while sick, and needing to be hospitalized. People who could work from home, whose companies had policies to prevent infections, and who took steps to avoid getting infected needed less medical care and missed work less often. This information may be used to help develop policies, communications, and guidance to prevent COVID-19 and limit its impact on employers and workers.

The impact of vaccination and outpatient treatment on the economic burden of Covid-19 in the United States omicron era: a systematic literature review.

AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era. MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria. RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters. LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed. CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.

Impact of Bivalent BA.4/5 BNT162b2 COVID-19 Vaccine on Acute Symptoms, Quality of Life, Work Productivity and Activity Levels among Symptomatic US Adults Testing Positive for SARS-CoV-2 at a National Retail Pharmacy.

Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs). Symptomatic US adults testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023 (CT.gov NCT05160636). PROs were assessed using four questionnaires measuring symptoms, HRQoL and WPAI (a CDC-based symptom survey, PROMIS Fatigue, EQ-5D-5L, WPAI-GH), from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. The study included 643 participants: 316 vaccinated with BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance.

Estimated Effectiveness of Coadministration of the BNT162b2 BA.4/5 COVID-19 Vaccine With Influenza Vaccine.

Importance: No data comparing the estimated effectiveness of coadministering COVID-19 vaccines with seasonal influenza vaccine (SIV) in the community setting exist. Objective: To examine the comparative effectiveness associated with coadministering the BNT162b2 BA.4/5 bivalent mRNA COVID-19 vaccine (BNT162b2-biv [Pfizer BioNTech]) and SIV vs giving each vaccine alone. Design, Setting, and Participants: A retrospective comparative effectiveness study evaluated US adults aged 18 years or older enrolled in commercial health insurance or Medicare Advantage plans and vaccinated with BNT162b2-biv only, SIV only, or both on the same day between August 31, 2022, and January 30, 2023. Individuals with monovalent or another brand of mRNA bivalent COVID-19 vaccine were excluded. Exposure: Same-day coadministration of BNT162b2-biv and SIV; receipt of BNT162b2-biv only (for COVID-19-related outcomes) or SIV only (for influenza-related outcomes) were the comparator groups. For adults aged 65 years or older, only enhanced SIVs were included. Main Outcomes and Measures: COVID-19-related and influenza-related hospitalization, emergency department (ED) or urgent care (UC) encounters, and outpatient visits. Results: Overall, 3 442 996 individuals (57.0% female; mean [SD] age, 65 [16.7] years) were included. A total of 627 735 individuals had BNT162b2-biv and SIV vaccine coadministered, 369 423 had BNT162b2-biv alone, and 2 445 838 had SIV alone. Among those aged 65 years or older (n = 2 210 493; mean [SD] age, 75 [6.7] years; 57.9% female), the coadministration group had a similar incidence of COVID-19-related hospitalization (adjusted hazard ratio [AHR], 1.04; 95% CI, 0.87-1.24) and slightly higher incidence of emergency department or urgent care encounters (AHR, 1.12; 95% CI, 1.02-1.23) and outpatient visits (AHR, 1.06; 95% CI, 1.01-1.11) compared with the BNT162b2-biv-only group. Among individuals aged 18 to 64 years (n = 1 232 503; mean [SD] age, 47 [13.1] years; 55.4% female), the incidence of COVID-19-related outcomes was slightly higher among those who received both vaccines vs BNT162b2-biv alone (AHR point estimate range, 1.14-1.57); however, fewer events overall in this age group resulted in wider CIs. Overall, compared with those who received SIV alone, the coadministration group had a slightly lower incidence of most influenza-related end points (AHR point estimates 0.83-0.93 for those aged ≥65 years vs 0.76-1.08 for those aged 18-64 years). Negative control outcomes suggested residual bias and calibration of COVID-19-related and influenza-related outcomes with negative controls moved all estimates closer to the null, with most CIs crossing 1.00. Conclusions and Relevance: In this study, coadministration of BNT162b2-biv and SIV was associated with generally similar effectiveness in the community setting against COVID-19-related and SIV-related outcomes compared with giving each vaccine alone and may help improve uptake of both vaccines.

Impact of COVID-19 Infection on Health-Related Quality of Life, Work Productivity and Activity Impairment by Symptom-Based Long COVID Status and Age in the US.

COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups.

Clinical outcomes of COVID-19 and influenza in hospitalized children <5 years in the US.

Introduction: We compared hospitalization outcomes of young children hospitalized with COVID-19 to those hospitalized with influenza in the United States. Methods: Patients aged 0-<5 years hospitalized with an admission diagnosis of acute COVID-19 (April 2021-March 2022) or influenza (April 2019-March 2020) were selected from the PINC AI Healthcare Database Special Release. Hospitalization outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, and mechanical ventilation (MV). Inverse probability of treatment weighting was used to adjust for confounders in logistic regression analyses. Results: Among children hospitalized with COVID-19 (n = 4,839; median age: 0 years), 21.3% had an ICU admission, 19.6% received oxygen supplementation, 7.9% received MV support, and 0.5% died. Among children hospitalized with influenza (n = 4,349; median age: 1 year), 17.4% were admitted to the ICU, 26.7% received oxygen supplementation, 7.6% received MV support, and 0.3% died. Compared to children hospitalized with influenza, those with COVID-19 were more likely to have an ICU admission (adjusted odds ratio [aOR]: 1.34; 95% confidence interval [CI]: 1.21-1.48). However, children with COVID-19 were less likely to receive oxygen supplementation (aOR: 0.71; 95% CI: 0.64-0.78), have a prolonged LOS (aOR: 0.81; 95% CI: 0.75-0.88), or a prolonged ICU stay (aOR: 0.56; 95% CI: 0.46-0.68). The likelihood of receiving MV was similar (aOR: 0.94; 95% CI: 0.81, 1.1). Conclusions: Hospitalized children with either SARS-CoV-2 or influenza had severe complications including ICU admission and oxygen supplementation. Nearly 10% received MV support. Both SARS-CoV-2 and influenza have the potential to cause severe illness in young children.

Assessment of retrospective collection of EQ-5D-5L in a US COVID-19 population.

BACKGROUND: It is imperative to evaluate health related quality of life (HRQoL) pre-COVID-19, but there is currently no evidence of the retrospective application of the EuroQol 5-Dimension, 5 level version (EQ-5D-5L) for COVID-19 studies. METHODS: Symptomatic patients with SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022-04/30/2022. Consented participants completed the EQ-5D-5L questionnaire twice: a modified version where all the questions were past tense to retrospectively assess pre-COVID-19 baseline QoL, and the standard version in present tense to assess current HRQoL. Duncan's new multiple range test was adopted for post analysis of variance pairwise comparisons of EQ visual analog scale (EQ VAS) means between problem levels for each of 5 domains. A linear mixed model was applied to check whether the relationship between EQ VAS and utility index (UI) was consistent pre-COVID-19 and during COVID-19. Matching-adjusted indirect comparison was used to compare pre-COVID-19 UI and EQ VAS scores with those of the US population. Lastly, Cohen's d was used to quantify the magnitude of difference in means between two groups. RESULTS: Of 676 participants, 10.2% were age 65 or more years old, 73.2% female and 71.9% white. Diabetes was reported by 4.7% participants and hypertension by 11.2%. The estimated coefficient for the interaction of UI-by-retrospective collection indicator (0 = standard prospective collection, 1 = retrospective for pre-COVID-19), -4.2 (SE: 3.2), P = 0.197, indicates that retrospective collection does not significantly alter the relationship between EQ VAS and UI. After adjusting for age, gender, diabetes, hypertension, and percent of mobility problems, the predicted means of pre-COVID-19 baseline EQ VAS and UI were 84.6 and 0.866, respectively. Both means were close to published US population norms (80.4 and 0.851) compared to those observed (87.4 and 0.924). After adjusting for age, gender, diabetes, and hypertension, the calculated ES between pre-COVID-19 and COVID-19 for UI and EQ VAS were 0.15 and 0.39, respectively. Without retrospectively collected EQ-5D-5L, using US population norms tended to underestimate the impact of COVID-19 on HRQoL. CONCLUSION: At a group level the retrospectively collected pre-COVID-19 EQ-5D-5L is adequate and makes it possible to directly evaluate the impact of COVID-19 on HRQoL. ( ClinicalTrials.gov NCT05160636).

Geographic variation in clinical outcomes and anticoagulation among medicare beneficiaries with non-valvular atrial fibrillation.

Oral anticoagulants (OACs) have been used to prevent stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF). To evaluate baseline clinical characteristics, incidence rates of stroke/SE and hospitalization for bleeding, and OAC use among elderly patients with NVAF in the US by geographic region. Patients with NVAF were selected from the US Centers for Medicare & Medicaid Services claims database (01JAN2013-31DEC2016). Twelve months of health plan enrollment was required before and after the NVAF diagnosis to evaluate baseline characteristics and outcomes, respectively. Each patient was assigned to a 3-digit zip code based on their primary residence, and geographic variation was visualized using ArcGIS Pro software. Over 2.8 million patients with NVAF were identified. Large geographic variation was observed in clinical characteristics, stroke/SE, hospitalization for bleeding, and OAC use among patients across the US. The zip codes with the highest mean CHA2DS2-VASc scores and frequency of prior bleeding also had the highest incidence of stroke/SE and hospitalization for bleeding. Across 3-digit zip codes, 35-63% of patients were untreated. Overall, the incidence of stroke/SE and hospitalization for bleeding were higher and OAC treatment was less frequent in zip codes located in the Southern US. Baseline clinical characteristics, incidence rates of stroke/SE and hospitalization for bleeding, and OAC usage vary considerably by 3-digit zip code in the US. The additional granularity provided in this study may help clinicians to identify small regions with high-risk of stroke/SE and hospitalization for bleeding and low use of OAC that may benefit from targeted care strategies.

Impact of COVID-19 and effects of booster vaccination with BNT162b2 on six-month long COVID symptoms, quality of life, work productivity and activity impairment during Omicron.

BACKGROUND: Longitudinal estimates of long COVID burden during Omicron remain limited. This study characterized long-term impacts of COVID-19 and booster vaccination on symptoms, Health-Related Quality of Life (HRQoL), and Work Productivity Activity Impairment (WPAI). METHODS: Outpatients with ≥ 1 self-reported symptom and positive SARS-CoV-2 test at CVS Health United States test sites were recruited between 01/31 and 04/30/2022. Symptoms, EQ-5D and WPAI were collected via online surveys until 6 months following infection. Both observed and model-based estimates were analyzed. Effect sizes based on Cohen's d quantified the magnitude of outcome changes over time, within and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for covariates. Logistic regression assessed odds ratio (OR) of long COVID between vaccination groups. RESULTS: At long COVID start (Week 4), 328 participants included 87 (27%) Boosted with BNT162b2, 86 (26%) with a BNT162b2 primary series (Primed), and 155 (47%) Unvaccinated. Mean age was 42.0 years, 73.8% were female, 26.5% had ≥ 1 comorbidity, 36.9% prior infection, and 39.6% reported ≥ 3 symptoms (mean: 3.1 symptoms). At Month 6, among 260 participants, Boosted reported a mean of 1.1 symptoms versus 3.4 and 2.8 in Unvaccinated and Primed, respectively (p < 0.001). Boosted had reduced risks of ≥ 3 symptoms versus Unvaccinated (observed: OR 0.22, 95% CI 0.10-0.47, p < 0.001; model-based: OR 0.36, 95% CI 0.15-0.87, p = 0.019) and Primed (observed: OR 0.29, 95% CI 0.13-0.67, p = 0.003; model-based: OR 0.59, 95% CI 0.21-1.65, p = 0.459). Results were consistent using ≥ 2 symptoms. Regarding HRQoL, among those with long COVID, Boosted had higher EQ-5D Utility Index (UI) than Unvaccinated (observed: 0.922 vs. 0.731, p = 0.014; model-based: 0.910 vs. 0.758, p-value = 0.038) and Primed (0.922 vs. 0.648, p = 0.014; model-based: 0.910 vs. 0.708, p-value = 0.008). Observed and model-based estimates for EQ-VAS and UI among Boosted were comparable with pre-COVID since Month 3. Subjects vaccinated generally reported better WPAI scores. CONCLUSIONS: Long COVID negatively impacted HRQoL and WPAI. The BNT162b2 booster could have a beneficial effect in reducing the risk and burden of long COVID. Boosted participants reported fewer and less durable symptoms, which contributed to improve HRQoL and maintain WPAI levels. Limitations included self-reported data and small sample size for WPAI.

The impact of COVID-19 vaccination in the US: Averted burden of SARS-COV-2-related cases, hospitalizations and deaths.

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

Public health impact and economic value of booster vaccination with Pfizer-BioNTech COVID-19 vaccine, bivalent (Original and Omicron BA.4/BA.5) in the United States.

OBJECTIVE: To assess the public health impact and economic value of booster vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent in the United States. METHODS: A combined cohort Markov decision tree model estimated the cost-effectiveness and budget impact of booster vaccination compared to no booster vaccination in individuals aged ≥5 years. Analyses prospectively assessed three scenarios (base case, low, high) defined based upon the emergence (or not) of subvariants, using list prices. Age-stratified parameters were informed by literature. The cost-effectiveness analysis estimated cases, hospitalizations and deaths averted, Life Years (LYs) and Quality Adjusted Life Years (QALYs) gained, the incremental cost-effectiveness ratio (ICER), the net monetary benefit (NMB), and the Return on Investment (ROI). The budget impact analyses used the perspective of a hypothetical 1-million-member plan. Sensitivity analyses explored parameter uncertainty. Conservatively, indirect effects and broad societal benefits were not considered. RESULTS: The base case predicted that, compared to no booster vaccination, the Pfizer-BioNTech COVID-19 Vaccine, Bivalent could result in ∼3.7 million fewer symptomatic cases, 162 thousand fewer hospitalizations, 45 thousand fewer deaths, 373 thousand fewer discounted QALYs lost, and was cost-saving. Using a conservative value of $50,000 for 1 LY, every $1 invested yielded estimated $4.67 benefits. Unit costs, health outcomes and effectiveness had the greatest impact on results. At $50,000 per QALY gained, the booster generated a 34.2 billion NMB and probabilistic sensitivity analyses indicated a 92% chance of being cost-saving and 98% of being cost-effective. The bivalent was cost-saving or highly cost-effective in high and low scenarios. In a hypothetical 1-million-member health plan population, the vaccine was predicted to be a budget-efficient solution for payers. CONCLUSIONS: Booster vaccination with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent for the US population aged ≥5 years could generate notable public health impact and be cost-saving based on the findings of our base case analyses.

The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as a Case Study.

Health technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted, combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements ongoing efforts aimed towards a broader recognition of the full societal value of vaccines.

Effectiveness and Safety of Direct Oral Anticoagulants Among Patients with Non-valvular Atrial Fibrillation and Multimorbidity.

INTRODUCTION: In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs). METHODS: Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard ratios of S/SE and MB among three 1:1 propensity score matched DOAC cohorts. All-cause healthcare costs were estimated using generalized linear models. RESULTS: Overall 36% of the NVAF study population had high multimorbidity, forming three propensity score matched (PSM) cohorts: 12,511 apixaban-dabigatran, 60,287 apixaban-rivaroxaban, and 12,567 dabigatran-rivaroxaban patients. Apixaban was associated with a lower risk of stroke/SE and MB when compared with dabigatran and rivaroxaban. Dabigatran had a lower risk of stroke/SE and a similar risk of MB when compared with rivaroxaban. Compared to rivaroxaban, apixaban patients incurred lower all-cause healthcare costs, and dabigatran patients incurred similar all-cause healthcare costs. Compared to dabigatran, apixaban patients incurred similar all-cause healthcare costs. CONCLUSION: Patients with NVAF and ≥ 6 comorbid conditions had significantly different risks for stroke/SE and MB when comparing DOACs to DOACs, and different healthcare expenses. This study's results may be useful for evaluating the risk-benefit ratio of DOAC use in patients with NVAF and multimorbidity.

Estimated global public health and economic impact of COVID-19 vaccines in the pre-omicron era using real-world empirical data.

BACKGROUND: Limited data are available describing the global impact of COVID-19 vaccines. This study estimated the global public health and economic impact of COVID-19 vaccines before the emergence of the Omicron variant. METHODS: A static model covering 215 countries/territories compared the direct effects of COVID-19 vaccination to no vaccination during 13 December 2020-30 September 2021. After adjusting for underreporting of cases and deaths, base case analyses estimated total cases and deaths averted, and direct outpatient and productivity costs saved through averted health outcomes. Sensitivity analyses applied alternative model assumptions. RESULTS: COVID-19 vaccines prevented an estimated median (IQR) of 151.7 (133.7-226.1) million cases and 620.5 (411.1-698.1) thousand deaths globally through September 2021. In sensitivity analysis applying an alternative underreporting assumption, median deaths averted were 2.1 million. Estimated direct outpatient cost savings were $21.2 ($18.9-30.9) billion and indirect savings of avoided productivity loss were $135.1 ($121.1-206.4) billion, yielding a total cost savings of $155 billion globally through averted infections. CONCLUSIONS: Using a conservative modeling approach that considered direct effects only, we estimated that COVID-19 vaccines have averted millions of infections and deaths, generating billions of cost savings worldwide, which underscore the continued importance of vaccination in public health response to COVID-19.

Public health impact of UK COVID-19 booster vaccination programs during Omicron predominance.

BACKGROUND: We aimed to estimate the public health impact of booster vaccination against COVID-19 in the UK during an Omicron-predominant period. RESEARCH DESIGN AND METHODS: A dynamic transmission model was developed to compare public health outcomes for actual and alternative UK booster vaccination programs. Input sources were publicly available data and targeted literature reviews. Base case analyses estimated outcomes from the UK's Autumn-Winter 2021-2022 booster program during January-March 2022, an Omicron-predominant period. Scenario analyses projected outcomes from Spring and in Autumn 2022 booster programs over an extended time horizon from April 2022-April 2023, assuming continued Omicron predominance, and explored hypothetical program alternatives with modified eligibility criteria and/or increased uptake. RESULTS: Estimates predicted that the Autumn-Winter 2021-2022 booster program averted approximately 12.8 million cases, 1.1 million hospitalizations, and 290,000 deaths. Scenario analyses suggested that Spring and Autumn 2022 programs would avert approximately 6.2 million cases, 716,000 hospitalizations, and 125,000 deaths; alternatives extending eligibility or targeting risk groups would improve these benefits, and increasing uptake would further strengthen impact. CONCLUSIONS: Boosters were estimated to provide substantial benefit to UK public health during Omicron predominance. Benefits of booster vaccination could be maximized by extending eligibility and increasing uptake.

Impact of COVID-19 and effects of BNT162b2 on patient-reported outcomes: quality of life, symptoms, and work productivity among US adult outpatients.

BACKGROUND: Although there is extensive literature on the clinical benefits of COVID-19 vaccination, data on humanistic effects are limited. This study evaluated the impact of SARS-CoV-2 infection on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Impairment (WPAI) prior to and one month following infection between individuals vaccinated with BNT162b2 and those unvaccinated. METHODS: Subjects with ≥ 1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between 01/31/2022 and 04/30/2022. Socio-demographics, clinical characteristics and vaccination status were evaluated. Self-reported symptoms, HRQoL, and WPAI outcomes were assessed using questionnaires and validated instruments (EQ-5D-5L, WPAI-GH) across acute COVID time points from pre-COVID to Week 4, and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for several covariates. Effect size (ES) of Cohen's d was calculated to quantify the magnitude of outcome changes within and between vaccination groups. RESULTS: The study population included 430 subjects: 197 unvaccinated and 233 vaccinated with BNT162b2. Mean (SD) age was 42.4 years (14.3), 76.0% were female, 38.8% reported prior infection and 24.2% at least one comorbidity. Statistically significant differences in outcomes were observed compared with baseline and between groups. The EQ-Visual analogue scale scores and Utility Index dropped in both cohorts at Day 3 and increased by Week 4 but did not return to pre-COVID levels. The mean changes were statistically lower in the BNT162b2 cohort at Day 3 and Week 4. The BNT162b2 cohort reported lower prevalence and fewer symptoms at index date and Week 4. At Week 1, COVID-19 had a large impact on all WPAI-GH domains: the work productivity time loss among unvaccinated and vaccinated was 65.0% and 53.8%, and the mean activity impairment was 50.2% and 43.9%, respectively. Except for absenteeism at Week 4, the BNT162b2 cohort was associated with statistically significant less worsening in all WPAI-GH scores at both Week 1 and 4. CONCLUSIONS: COVID-19 negatively impacted HRQoL and work productivity among mildly symptomatic outpatients. Compared with unvaccinated, those vaccinated with BNT162b2 were less impacted by COVID-19 infection and recovered faster.

Public health impact of booster vaccination against COVID-19 in the UK during Delta variant dominance in autumn 2021.

AIM: To evaluate the public health impact of the UK COVID-19 booster vaccination program in autumn 2021, during a period of SARS-CoV-2 Delta variant predominance. MATERIALS AND METHODS: A compartmental Susceptible-Exposed-Infectious-Recovered model was used to compare age-stratified health outcomes for adult booster vaccination versus no booster vaccination in the UK over a time horizon of September-December 2021, when boosters were introduced in the UK and the SARS-CoV-2 Delta variant was predominant. Model input data were sourced from targeted literature reviews and publicly available data. Outcomes were predicted COVID-19 cases, hospitalizations, post-acute sequelae of COVID-19 (PASC) cases, deaths, and productivity losses averted, and predicted healthcare resources saved. Scenario analyses varied booster coverage, virus infectivity and severity, and time horizon parameters. RESULTS: Booster vaccination was estimated to have averted approximately 547,000 COVID-19 cases, 36,000 hospitalizations, 147,000 PASC cases, and 4,200 deaths in the UK between September and December 2021. It saved over 316,000 hospital bed-days and prevented the loss of approximately 16.5 million paid and unpaid patient work days. In a scenario of accelerated uptake, the booster rollout would have averted approximately 3,400 additional deaths and 25,500 additional hospitalizations versus the base case. A scenario analysis assuming four-fold greater virus infectivity and lower severity estimated that booster vaccination would have averted over 105,000 deaths and over 41,000 hospitalizations versus the base case. A scenario analysis assuming pediatric primary series vaccination prior to adult booster vaccination estimated that expanding vaccination to children aged ≥5 years would have averted approximately 51,000 additional hospitalizations and 5,400 additional deaths relative to adult booster vaccination only. LIMITATIONS: The model did not include the wider economic burden of COVID-19, hospital capacity constraints, booster implementation costs, or non-pharmaceutical interventions. CONCLUSIONS: Booster vaccination during Delta variant predominance reduced the health burden of SARS-CoV-2 in the UK, releasing substantial NHS capacity.

Public health impact of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) in the first year of rollout in the United States.

BACKGROUND: As the body of evidence on COVID-19 and post-vaccination outcomes continues to expand, this analysis sought to evaluate the public health impact of the Pfizer-BioNTech COVID-19 Vaccine, BNT162b2, during the first year of its rollout in the US. METHODS: A combined Markov decision tree model compared clinical and economic outcomes of the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) versus no vaccination in individuals aged ≥12 years. Age-stratified epidemiological, clinical, economic, and humanistic parameters were derived from existing data and published literature. Scenario analysis explored the impact of using lower and upper bounds of parameters on the results. The health benefits were estimated as the number of COVID-19 symptomatic cases, hospitalizations and deaths averted, and Quality Adjusted Life Years (QALYs) saved. The economic benefits were estimated as the amount of healthcare and societal cost savings associated with the vaccine-preventable health outcomes. RESULTS: It was estimated that, in 2021, the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to averting almost 9 million symptomatic cases, close to 700,000 hospitalizations, and over 110,000 deaths, resulting in an estimated $30.4 billion direct healthcare cost savings, $43.7 billion indirect cost savings related to productivity loss, as well as discounted gains of 1.1 million QALYs. Scenario analyses showed that these results were robust; the use of alternative plausible ranges of parameters did not change the interpretation of the findings. CONCLUSIONS: The Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) contributed to generate substantial public health impact and vaccine-preventable cost savings in the first year of its rollout in the US. The vaccine was estimated to prevent millions of COVID-19 symptomatic cases and thousands of hospitalizations and deaths, and these averted outcomes translated into cost-savings in the billions of US dollars and thousands of QALYs saved. As only direct impacts of vaccination were considered, these estimates may be conservative.