Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Modelling COVID-19 Vaccination in the UK: Impact of the Autumn 2022 and Spring 2023 Booster Campaigns.

INTRODUCTION: The delivery of COVID-19 vaccines was successful in reducing hospitalizations and mortality. However, emergence of the Omicron variant resulted in increased virus transmissibility. Consequently, booster vaccination programs were initiated to decrease the risk of severe disease and death among vulnerable members of the population. This study aimed to estimate the effects of the booster program and alternative vaccination strategies on morbidity and mortality due to COVID-19 in the UK. METHOD: A Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to assess the impact of several vaccination strategies on severe outcomes associated with COVID-19, including hospitalizations, mortality, National Health Service (NHS) capacity quantified by hospital general ward and intensive care unit (ICU) bed days, and patient productivity. The model accounted for age-, risk- and immunity-based stratification of the UK population. Outcomes were evaluated over a 48-week time horizon from September 2022 to August 2023 considering the actual UK autumn 2022/spring 2023 booster campaigns and six counterfactual strategies. RESULTS: The model estimated that the autumn 2022/spring 2023 booster campaign resulted in a reduction of 18,921 hospitalizations and 1463 deaths, compared with a no booster scenario. Utilization of hospital bed days due to COVID-19 decreased after the autumn 2022/spring 2023 booster campaign. Expanding the booster eligibility criteria and improving uptake improved all outcomes, including averting twice as many ICU admissions, preventing more than 20% additional deaths, and a sevenfold reduction in long COVID, compared with the autumn 2022/spring 2023 booster campaign. The number of productive days lost was reduced by fivefold indicating that vaccinating a wider population has a beneficial impact on the morbidities associated with COVID-19. CONCLUSION: Our modelling demonstrates that the autumn 2022/spring 2023 booster campaign reduced COVID-19-associated morbidity and mortality. Booster campaigns with alternative eligibility criteria warrant consideration in the UK, given their potential to further reduce morbidity and mortality as future variants emerge.

Soil microbial diversity and composition response to degradation of the alpine meadow in the southeastern Qinghai-Tibet Plateau.

With the interaction between global climate change and unreasonable human utilization, the alpine meadows on the Qinghai-Tibet Plateau have suffered various weathering degrees. Uncovering the degradation mechanism and restoration strategies can be facilitated by gaining insights into the diversity of soil microflora during meadow degradation. Therefore, we used Illumina sequencing technology to investigate the patterns of soil microbial diversity, microbial community composition, and the driving factors of microbial change in all non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and severely degraded (SD) alpine meadows in the southeastern Qinghai-Tibet Plateau. Our results pointed out that with the intensification of degradation, vegetation characteristics were significantly reduced, and soil parameters significantly varied among all degraded meadows. The contents of soil organic carbon (SOC), total nitrogen (TN), available phosphorus (AN), and total phosphorous (AK) in soils decreased with the increase of degradation. The dominant bacterial phyla were the same regardless of the meadow degradation level with Actinobacteria (37.67%) and Proteobacteria (20.62%) having the highest relative abundance. Meanwhile, the dominant fungi were Ascomycota (49.9%). Based on the linear discriminant analysis (LDA) and effect size (LEfSe) method, 38 bacterial and 49 fungal species were found to be affected in the degraded alpine meadow, most of which belonged to Actinobacteria and Ascomycota, respectively. Mantel test analysis illustrated that the bacterial community was mainly significantly dependent on below-ground biomass, pH, soil organic carbon, and total nitrogen, while the fungal community was significantly dependent on soil organic carbon, total nitrogen, available nitrogen, and available potassium. These results suggest that the degeneration of alpine meadows contributes to the variability of the diversity and composition of microflora on the Tibetan plateau. Yet this effect is mainly dependent on soil factors.

Duration of SARS-CoV-2 shedding: A systematic review.

Background: Positive viral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cultures indicate shedding of infectious virus and corresponding transmission risk of coronavirus disease 2019 (COVID-19). The research question of this systematic review was: Is there a discernible pattern in the timing of SARS-CoV-2 virus isolation, and what is the proportion of positive and negative results for isolation of SARS-CoV-2 virus with viral culture relative to the onset of clinical symptoms or the day of diagnosis, as indicated by longitudinal studies? Methods: We systematically searched PubMed and Embase from inception to 16 February 2023 for English-language studies with serial viral culture testing within symptomatic or asymptomatic SARS-CoV-2 infected persons during the post-vaccination period. Outcomes of interest were the daily culture status per study and the overall daily culture positivity rate of SARS-CoV-2. We critically appraised the selected studies using the Newcastle-Ottawa quality assessment scale. Results: We included 14 viral shedding studies in this systematic review. Positive viral SARS-CoV-2 cultures were detected in samples ranging from 4 days before to 18 days after symptom onset. The daily culture SARS-CoV-2 positivity rate since symptom onset or diagnosis showed a steep decline between day 5 and 9, starting with a peak ranging from 44% to 50% on days -1 to 5, decreasing to 28% on day 7 and 11% on day 9, and finally ranging between 0% and 8% on days 10-17. Conclusions: Viral shedding peaked within 5 days since symptom onset or diagnosis and the culture positivity rate rapidly declined hereafter. This systematic review provides an overview of current evidence on the daily SARS-CoV-2 culture positivity rates during the post-vaccination period. These findings could be used to estimate the effectiveness of public health control measures, including treatment and preventive strategies, to reduce the spread of COVID-19.

COVID-19-related work absenteeism and associated lost productivity cost in Germany: a population-based study.

OBJECTIVE: To estimate COVID-19 absenteeism and indirect costs, by care setting. METHODS: A population-based retrospective cohort study using data from the German Statutory Health Insurance (SHI) database to define outpatient (April 2020-December 2021) and hospitalized (April 2020-October 2022) cohorts of employed working-aged individuals. RESULTS: In the outpatient cohort (n = 369,220) median absenteeism duration and associated cost was 10.0 (IQR: 5.0, 15.0) days and €1,061 (530, 1,591), respectively. In the hospitalized cohort (n = 20,687), median absenteeism and associated cost was 15.0 (7.0, 32.0) days and €1,591 (743, 3,394), respectively. Stratified analyses showed greater absenteeism in older workers, those at risk and those with severe disease. CONCLUSIONS: The hospitalized cohort had longer absenteeism resulting in higher productivity loss. Being older, at risk of severe COVID-19 and higher disease severity during hospitalization were important drivers of higher absenteeism duration.

A Histopathologic Image Analysis for the Classification of Endocervical Adenocarcinoma Silva Patterns Depend on Weakly Supervised Deep Learning.

Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.

Cost-effectiveness analysis of COVID-19 booster vaccination with BNT162b2 in Japan.

BACKGROUND: The aim of this study was to evaluate the public health and economic impact of the COVID-19 booster vaccination with BNT162b2 in Japan during an Omicron-dominant period from early 2022. RESEARCH DESIGN AND METHODS: A combined cohort Markov decision tree model estimated the cost-effectiveness of annual or biannual booster vaccination strategies compared to no booster vaccination for those aged 65 years and above, and those aged 60-64 years at high risk as the base case. The societal perspective was primarily considered. We also examined other target populations with different age and risk groups. Sensitivity and scenario analyses with alternative inputs were performed. RESULTS: Annual and biannual vaccination strategies were dominant from the societal perspective in the base case. Incremental Cost Effectiveness Ratios (ICERs) from the payer perspective were JPY 1,752,499/Quality Adjusted Life Year (QALY) for annual vaccination and JPY 2,831,878/QALY for biannual vaccination, both less than the threshold value in Japan (JPY 5 million/QALY). The results were consistent even when examining other target age and risk groups. All sensitivity and scenario analyses indicated that ICERs were below JPY 5 million/QALY. CONCLUSIONS: Booster vaccination with the COVID-19 vaccine BNT162b2 is a dominant strategy and beneficial to public health in Japan.

Therapeutic effect and mechanism of Yougui Wan in rats with intervertebral disk degeneration.

OBJECTIVE: To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method. RESULTS: Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P < 0.05), the protein expression levels of collagen II were decreased, and the protein expression levels of Notch1 were increased. Compared with those in the model group, the levels of IL-10 in the TCM group were increased (P < 0.05), the levels of MIF and TNF-α were decreased (P < 0.05), the protein expression levels of collagen II were increased, and the protein expression levels of Notch1 were decreased. CONCLUSION: Yougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway.

Persons diagnosed with COVID-19 in England in the Clinical Practice Research Datalink (CPRD): a cohort description.

OBJECTIVE: To create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England. DESIGN: Retrospective cohort study. SETTING: Electronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England. PARTICIPANTS: 2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022. MAIN OUTCOME MEASURES: Age, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 'COVID-19'). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination). RESULTS: Compared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65-84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score. CONCLUSIONS: CPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.

Definition and measurement of post-COVID-19 conditions in real-world practice: a global systematic literature review.

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source. METHODS: Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022. FINDINGS: Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to <6 months (39.2%), followed by 6 to <12 months (27.5%) and <3 months (22.9%). When classified by organ/system, constitutional-related PCC were the most frequently assessed in adult (86%) and paediatric (87%) populations. Within constitutional symptoms, fatigue was most frequently assessed in adult (91.6%) and paediatric (95.0%) populations, followed by fever/chills (37.9% and 55%, respectively). CONCLUSIONS: PCC definitions are heterogenous across real-world studies, which limits reliable comparisons between studies. However, some similarities were observed in terms of the most frequently measured PCC-associated symptoms/conditions, which may aid clinical management of patients with PCC.CRD42022376111.

The Impact of Biosimilar Use on Total Cost of Care and Provider Financial Performance in the Medicare Oncology Care Model: A Population-Based Simulation Study.

INTRODUCTION: Payment for oncology care is increasingly moving from fee-for-service to value-based payment (VBP). VBPs are agreements in which providers are held accountable for total cost of care (TCOC) through risk-sharing arrangements with payers that tie reimbursement levels to TCOC benchmarks. Oncology biosimilars may play an important role in managing financial risk in the VBPs like Medicare's Oncology Care Model (OCM), but there has been limited research in this area. The objective of this study is to estimate the impact of biosimilar adoption on TCOC and oncology provider financial performance under the terms of the Medicare OCM. METHODS: We conducted a population-based simulation study using the Medicare Limited Data Set (LDS) and the methodology of Medicare's OCM. The primary outcome was the simulated average change in TCOC per 6-month episode of care attributable to use of biosimilars as an alternative to reference products. The study population consisted of episodes of care in 2020 and using the reference product or corresponding biosimilar for bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, or pegfilgrastim. TCOC was calculated for each episode of care with use of reference products only and compared with TCOC with corresponding biosimilars. The simulation calculated TCOC outcomes in cohorts of 100 episodes sampled from the Medicare LDS study population using a Monte Carlo simulation with 10,000 iterations. RESULTS: Among the total of 8281 6-month oncology care episodes identified in the study period (initiating January 2020 to July 2020) in Medicare claims, 1586 (19.2%) episodes met OCM and study criteria and were included. Applying the simulation methods to these observed episodes, biosimilar substitution reduced mean TCOC per episode by $1193 (95% CI $583-1840). The cost reduction from biosimilars represented 2.4% of the average TCOC benchmark and led to a 15% reduction in the risk of providers needing to pay recoupments to Medicare for exceeding TCOC benchmarks. CONCLUSIONS: On the basis of our simulation study using observed Medicare claims and OCM criteria, we found that biosimilar substitution for reference products can significantly lower episode TCOC and improve provider financial performance under the terms of the largest value-based payment model implemented to date.

Modelling the Potential Public Health Impact of Different COVID-19 Vaccination Strategies with an Adapted Vaccine in Singapore.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has been a dynamically changing virus, requiring the development of adapted vaccines. This study estimated the potential public health impact alternative vaccination strategies for COVID-19 in Singapore. RESEARCH DESIGN AND METHODS: The outcomes of alternative vaccination strategies with a future adapted vaccine were estimated using a combined Markov decision tree model. The population was stratified by high- and standard-risk. Using age-specific inputs informed by local surveillance data and published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 278,614 cases 21,558 hospitalizations, 239 deaths, Singapore dollars (SGD) 277 million in direct medical costs, and SGD 684 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (3%), hospitalizations (29%), infections (145%), direct costs (90%), and indirect costs (192%) compared to the base case. CONCLUSIONS: Broader vaccination strategies using an adapted booster vaccine could have substantial public health and economic impact in Singapore.

Health Care Resource Utilization and Costs Associated With COVID-19 Among Pediatrics Managed in the Community or Hospital Setting in England: A Population-based Cohort Study.

BACKGROUND: Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial health care resource burden. This study aimed to describe health care resource utilization (HCRU) and costs associated with COVID-19 in pediatrics 1-17 years old in England. METHODS: A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care secondary care data. HCRU and associated costs to the National Health Service were stratified by age, risk of severe COVID-19 and immunocompromised status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). RESULTS: This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those 1-4 years of age (face-to-face: 4.3%; telephone: 6.0%) compared with those 5-11 (2.0%; 2.1%) and 12-17 years of age (2.2%; 2.5%). In the hospitalized cohort, mean (SD) length of stay was longer [5.0 (5.8) days] among those 12-17 years old (n = 24) than those 1-4 [n = 15; 1.8 (0.9) days] and 5-11 years old [n = 21; 2.8 (2.1) days]. CONCLUSIONS: Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those 12-17 years old. Our results may help optimize the management and resource allocation of COVID-19 in this population.

Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study.

OBJECTIVES: To quantify direct costs and healthcare resource utilisation (HCRU) associated with acute COVID-19 in adults in England. DESIGN: Population-based retrospective cohort study using Clinical Practice Research Datalink Aurum primary care electronic medical records linked to Hospital Episode Statistics secondary care administrative data. SETTING: Patients registered to primary care practices in England. POPULATION: 1 706 368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13 105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1 693 263 within the primary care cohort indexed between August 2020 and January 2022. Patients with a COVID-19-related hospitalisation within 84 days of a positive test were included in the hospitalised cohort. MAIN OUTCOME MEASURES: Primary and secondary care HCRU and associated costs ≤4 weeks following positive COVID-19 test, stratified by age group, risk of severe COVID-19 and immunocompromised status. RESULTS: Among the hospitalised cohort, average length of stay, including critical care stays, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75-84 (£8942) and ≥85 years (£8835) than in those aged <50 years (£7703). While few (6.0%) patients in critical care required mechanical ventilation, its use was higher in older adults (50-74 years: 8.3%; <50 years: 4.3%). HCRU and associated costs were often greater in those at higher risk of severe COVID-19 than in the overall cohort, although minimal differences in HCRU were found across the three different high-risk definitions. Among the primary care cohort, general practitioner or nurse consultations were more frequent among older adults and the immunocompromised. CONCLUSIONS: COVID-19-related hospitalisations in older adults, particularly critical care stays, were the primary drivers of high COVID-19 resource use in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.

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.

Modelling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Thailand.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has continuously evolved, requiring the development of adapted vaccines. This study estimated the impact of the introduction and increased coverage of an Omicron-adapted bivalent booster vaccine in Thailand. RESEARCH DESIGN AND METHODS: The outcomes of booster vaccination with an Omicron-adapted bivalent vaccine versus no booster vaccination were estimated using a combined cohort Markov decision tree model. The population was stratified into high- and standard-risk subpopulations. Using age-specific inputs informed by published sources, the model estimated health (case numbers, hospitalizations, and deaths) and economic (medical costs and productivity losses) outcomes in different age and risk subpopulations. RESULTS: Booster vaccination in only the elderly and high-risk subpopulation was estimated to avert 97,596 cases 36,578 hospitalizations, 903 deaths, THB 3,119 million in direct medical costs, and THB 10,589 million in indirect medical costs. These benefits increased as vaccination was expanded to other subpopulations. Increasing the booster vaccination coverage to 75% of the standard-risk population averted more deaths (95%), hospitalizations (512%), infections (782%), direct costs (550%), and indirect costs (687%) compared to the base case. CONCLUSIONS: Broader vaccination with an Omicron-adapted bivalent booster vaccine could have significant public health and economic benefits in Thailand.

Impact of vaccination and non-pharmacological interventions on COVID-19: a review of simulation modeling studies in Asia.

Introduction: Epidemiological modeling is widely used to offer insights into the COVID-19 pandemic situation in Asia. We reviewed published computational (mathematical/simulation) models conducted in Asia that assessed impacts of pharmacological and non-pharmacological interventions against COVID-19 and their implications for vaccination strategy. Methods: A search of the PubMed database for peer-reviewed, published, and accessible articles in English was performed up to November 2022 to capture studies in Asian populations based on computational modeling of outcomes in the COVID-19 pandemic. Extracted data included model type (mechanistic compartmental/agent-based, statistical, both), intervention type (pharmacological, non-pharmacological), and procedures for parameterizing age. Findings are summarized with descriptive statistics and discussed in terms of the evolving COVID-19 situation. Results: The literature search identified 378 results, of which 59 met criteria for data extraction. China, Japan, and South Korea accounted for approximately half of studies, with fewer from South and South-East Asia. Mechanistic models were most common, either compartmental (61.0%), agent-based (1.7%), or combination (18.6%) models. Statistical modeling was applied less frequently (11.9%). Pharmacological interventions were examined in 59.3% of studies, and most considered vaccination, except one study of an antiviral treatment. Non-pharmacological interventions were also considered in 84.7% of studies. Infection, hospitalization, and mortality were outcomes in 91.5%, 30.5%, and 30.5% of studies, respectively. Approximately a third of studies accounted for age, including 10 that also examined mortality. Four of these studies emphasized benefits in terms of mortality from prioritizing older adults for vaccination under conditions of a limited supply; however, one study noted potential benefits to infection rates from early vaccination of younger adults. Few studies (5.1%) considered the impact of vaccination among children. Conclusion: Early in the COVID-19 pandemic, non-pharmacological interventions helped to mitigate the health burden of COVID-19; however, modeling indicates that high population coverage of effective vaccines will complement and reduce reliance on such interventions. Thus, increasing and maintaining immunity levels in populations through regular booster shots, particularly among at-risk and vulnerable groups, including older adults, might help to protect public health. Future modeling efforts should consider new vaccines and alternative therapies alongside an evolving virus in populations with varied vaccination histories.

Burden of COVID-19 during the omicron predominance in Brazil: a nationwide retrospective database study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has imposed significant burden on Brazil's health system. This study aimed to examine clinical characteristics, overall vaccine uptake, and to assess healthcare resource utilization (HCRU) and costs associated with acute COVID-19 in Brazil during the Omicron predominant period. METHODS: A nationwide retrospective study was conducted using various Brazilian databases including, COVID-19 related databases, public health systems, and other surveillance/demographic datasets. Individuals with positive COVID-19 test results between January 1 2022 and April 30 2022, during Omicron BA.1/BA.2 wave, were identified. Patients' demographics, vaccine uptake, HCRU and corresponding costs were described by age groups. RESULTS: A total of 8,160,715 (3.80%) COVID-19 cases were identified in the study cohort, ranging from 2.43% in <5 years to 62.05% in 19-49 years. The uptake of partial (Dose 1) or full immunization (Dose 2) was less than 0.1% in children aged <5 years, whereas in individuals ≥ 19 years, it exceeded 89.78% for Dose 1 and 84.07% for Dose 2. Overall booster vaccine uptake was 38.06%, which was significantly higher among individuals aged ≥ 65 years, surpassing 74.79%. Regardless of vaccination status, 87.2% cases were symptomatic, and 1.48% were hospitalized due to acute COVID-19 (<5 years: 2.33%, 5-11 years: 0.99%, 12-18 years: 0.32%, 19-49 years: 0.40%; 50-64 years: 1.50%, 65-74 years: 5.43%, and ≥ 75 years: 17.89%). Among the hospitalized patients (n = 120,450), 32.57% were admitted to ICU, of whom 31,283 (79.75%) individuals required mechanical ventilation (MV) support. The average cost per day in normal ward and ICU without MV in public/general hospital settings was $104.36 and $302.81, respectively. While average cost per day in normal ward and ICU with MV was $75.91 and $301.22 respectively. CONCLUSIONS: This study quantified the burden of COVID-19 in Brazil, suggesting substantial healthcare resources required to manage the COVID-19 pandemic.

Modeling the potential public health impact of different vaccination strategies with an omicron-adapted bivalent vaccine in Malaysia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) case numbers have increased following the emergence of the Omicron variant. This study estimated the impact of introducing and increasing the coverage of an Omicron-adapted bivalent booster vaccine in Malaysia. RESEARCH DESIGN AND METHODS: A combined cohort Markov decision tree model was used to compare booster vaccination with an Omicron-adapted bivalent COVID-19 vaccine versus no booster vaccination in Malaysia. The model utilized age-specific data from January 2021 to March 2022 derived from published sources. The outcomes of interest included case numbers, hospitalizations, deaths, medical costs, and productivity losses. The population was stratified into high-risk and standard-risk subpopulations, and the study evaluated the benefits of increased coverage in different age and risk groups. RESULTS: Vaccinating only high-risk individuals and those aged ≥ 65 years was estimated to avert 274,313 cases, 33229 hospitalizations, 2,434 deaths, Malaysian ringgit (MYR) 576 million in direct medical costs, and MYR 579 million in indirect costs. Expanding vaccination coverage in the standard-risk population to 75% was estimated to avert more deaths (31%), hospitalizations (155%), infections (206%), direct costs (206%), and indirect costs (281%). CONCLUSIONS: These findings support broader population Omicron-adapted bivalent booster vaccination in Malaysia with potential for significant health and economic gains.