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.

Ceftaroline Fosamil for the Treatment of Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Real-World Comparative Clinical Outcomes Study.

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in substantial morbidity and mortality. As current treatments often lead to unsatisfactory outcomes, evidence guiding alternative treatment options is needed. This study evaluated real-world clinical outcomes of ceftaroline fosamil for the treatment of MRSA bacteremia. METHODS: This retrospective study included adults hospitalized with MRSA bacteremia between 2011 and 2019. Patients were classified according to treatment with ceftaroline fosamil (ceftaroline), vancomycin, or daptomycin: Group 1, ceftaroline; Group 2, vancomycin or daptomycin (without ceftaroline); Group 3, combination therapy with ≥ 2 of these three agents. Clinical outcomes were compared using propensity-score-adjusted odds ratios (ORs) from logistic regression models. RESULTS: Overall, 24,479 patients were included (Group 1, n = 532; Group 2, n = 21,555; Group 3, n = 2392). Mean age was 59.6, 60.8, and 57.4 years in Groups 1, 2, and 3, respectively. Mean post-index treatment length of stay was 8.8, 8.8, and 8.0 days, respectively. The most frequent line of therapy was ceftaroline first-line (42.1%), vancomycin or daptomycin first-line (95.4%), and combination therapy third-line or later (67.8%) in Groups 1, 2, and 3, respectively. Compared with Group 2, Groups 1 and 3 had similar favorable clinical responses {odds ratio [OR] = 1.18 [95% confidence interval (CI) 0.98-1.44], p = 0.08; OR = 1.20 [95% CI 0.97-1.47], p = 0.09, respectively} and were less likely to switch treatment (both p < 0.001). Compared with Group 2, Group 1 was more likely to undergo 30-day all-cause readmission [OR = 1.38 (95% CI 1.06-1.80), p = 0.02], whereas this was less likely for Group 3 [OR = 0.77 (95% CI 0.58-1.00), p = 0.05]. CONCLUSIONS: Patients receiving ceftaroline more often had favorable clinical responses than those receiving vancomycin or daptomycin monotherapy. In the absence of large-scale randomized controlled trials, these real-world data provide insights into the potential role of ceftaroline for treating MRSA bacteremia.

Examining the association of rurality with opioid-related morbidity and mortality in Georgia: A geospatial analysis.

INTRODUCTION: The US opioid epidemic continues to escalate, with overdose deaths being the most-used metric to quantify its burden. There is significant geographic variation in opioid-related outcomes. Rural areas experience unique challenges, yet many studies oversimplify rurality characterizations. Contextual factors, such as area deprivation, are also important to consider when understanding a community's need for treatment services and prevention programming. This study aims to provide a geospatial snapshot of the opioid epidemic in Georgia using several metrics of opioid-related morbidity and mortality and explore differences by rurality across counties. METHODS: This was a spatial ecologic study. Negative binominal regression was used to model the relationship of county rurality with four opioid-related outcomes - overdose mortality, emergency department visits, inpatient hospitalizations, and overdose reversals - adjusting for county-level sex, racial/ethnic, and age distributions. Area Deprivation Index was also included. RESULTS: There was significant geographic variation across the state for all four opioid-related outcomes. Counts remained highest among the metro areas. For rates, counties in the top quartile of rates varied by outcome and were often rural areas. In the final models, rurality designation was largely unrelated to opioid outcomes, with the exception of medium metro areas (inversely related to hospitalizations and overdose reversals) and non-core areas (inversely related to hospitalizations), as compared to large central metro areas. Higher deprivation was significantly related to increased ED visits and hospitalizations, but not overdose mortality and reversals. CONCLUSIONS: When quantifying the burden of the opioid epidemic in a community, it is essential to consider multiple outcomes of morbidity and mortality. Understanding what outcomes are problematic for specific communities, in combination with their demographic and socioeconomic context, can provide insight into gaps in the treatment continuum and potential areas for intervention. Additionally, compared to demographic and socioeconomic factors, rurality may no longer be a salient predictor of the severity of the opioid epidemic in an area.

COVID-19-Related Work Absenteeism and Associated Lost Productivity Cost in Germany: A Population-Based Study.

OBJECTIVE: The aim of the study is 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 (Q1, Q3: 5.0, 15.0) days and €1061 (530, 1591), respectively. In the hospitalized cohort ( n = 20,687), median absenteeism and associated cost was 15.0 (7.0, 32.0) days and €1591 (743, 3394), 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.

Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection.

BACKGROUND: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19. METHODS: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL. RESULTS: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (ß=-0.080, p = 0.001) and long COVID (ß=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (ß=-0.147, p = 0.026) and long (ß=-0.186, p < 0.001) COVID. CONCLUSION: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.

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.

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.

Cost-Effectiveness of Oral Nirmatrelvir/Ritonavir in Patients at High Risk for Progression to Severe COVID-19 in the United States.

OBJECTIVES: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective. METHODS: A cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results. RESULTS: NMV/r was found to decrease COVID-19 related hospitalizations (-0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (-$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold. CONCLUSIONS: NMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective.

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.

Impact of SARS-CoV-2 infective exacerbation of chronic obstructive pulmonary disease on clinical outcomes in a prospective cohort study of hospitalised adults.

OBJECTIVES: To determine whether acute exacerbations of chronic obstructive pulmonary disease (AECOPD) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have worse outcomes than AECOPD caused by other infectious agents or non-infective AECOPD (NI-COPD). DESIGN: A two-hospital prospective cohort study of adults hospitalised with acute respiratory disease. We compared outcomes with AECOPD and a positive test for SARS-CoV-2 (n = 816), AECOPD triggered by other infections (n = 3038) and NI-COPD (n = 994). We used multivariable modelling to adjust for potential confounders and assessed variation by seasons associated with different SARS-CoV-2 variants. SETTING: Bristol UK, August 2020-May 2022. PARTICIPANTS: Adults (≥18 y) hospitalised with AECOPD. MAIN OUTCOME MEASURES: We determined the risk of positive pressure support, longer hospital admission and mortality following hospitalisation with AECOPD due to non-SARS-CoV-2 infection compared with SARS-CoV-2 AECOPD and NI-COPD. RESULTS: Patients with SARS-CoV-2 AECOPD, in comparison to non-SARS-CoV-2 infective AECOPD or NI-COPD, more frequently required positive pressure support (18.5% and 7.5% vs. 11.7%, respectively), longer hospital stays (median [interquartile range, IQR]: 7 [3-15] and 5 [2-10] vs. 4 [2-9] days, respectively) and had higher 30-day mortality (16.9% and 11.1% vs. 5.9%, respectively) (all p < 0.001). In adjusted analyses, SARS-CoV-2 AECOPD was associated with a 55% (95% confidence interval [95% CI]: 24-93), 26% (95% CI: 15-37) and 35% (95% CI: 10-65) increase in the risk of positive pressure support, hospitalisation length and 30-day mortality, respectively, relative to non-SARS-CoV-2 infective AECOPD. The difference in risk remained similar during periods of wild-type, Alpha and Delta SARS-CoV-2 strain dominance, but diminished during Omicron dominance. CONCLUSIONS: SARS-CoV-2-related AECOPD had worse patient outcomes compared with non-SARS-CoV-2 AECOPD or NI-AECOPD, although the difference in risks was less pronounced during Omicron dominance.

Incidence and clinical outcomes of pneumonia in persons with down syndrome in the United States.

BACKGROUND: Persons with Down syndrome (DS) experience an increased risk of pneumonia. We determined the incidence and outcomes of pneumonia and relationship to underlying comorbidities in persons with and without DS in the United States. METHODS: This retrospective matched cohort study used de-identified administrative claims data from Optum. Persons with DS were matched 1:4 to persons without DS on age, sex, and race/ethnicity. Pneumonia episodes were analyzed for incidence, rate ratios and 95 % confidence intervals, clinical outcomes, and comorbidities. RESULTS: During 1-year follow-up among 33796 persons with and 135184 without DS, the incidence of all-cause pneumonia (pneumonia) was substantially higher among people with DS than those without DS (12427 vs. 2531 episodes/100000 person-years; 4.7-5.7 fold increase). Persons with DS and pneumonia were more likely to be hospitalized (39.4 % vs. 13.9 %) or admitted to the ICU (16.8 % vs. 4.8 %). Mortality was higher 1 year after first pneumonia (5.7 % vs. 2.4 %; P < 0.0001). Results were similar for episodes of pneumococcal pneumonia. Specific comorbidities were associated with pneumonia, particularly heart disease in children and neurologic disease in adults, which only partially mediated the effect of DS on pneumonia. CONCLUSIONS: Among persons with DS, incidence of pneumonia and associated hospitalizations were increased; mortality among those with pneumonia was comparable at 30 days, but higher at 1 year. DS should be considered an independent risk condition for pneumonia.

Seasonal trends in COVID-19 cases, hospitalizations, and mortality in the United States and Europe.

Determining whether SARS-CoV-2 exhibits seasonality like other respiratory viruses is critical for public health planning. We evaluated whether COVID-19 rates follow a seasonal pattern using time series models. We used time series decomposition to extract the annual seasonal component of COVID-19 case, hospitalization, and mortality rates from March 2020 through December 2022 for the United States and Europe. Models were adjusted for a country-specific stringency index to account for confounding by various interventions. Despite year-round disease activity, we identified seasonal spikes in COVID-19 from approximately November through April for all outcomes and in all countries. Our results support employing annual preventative measures against SARS-CoV-2, such as administering seasonal booster vaccines in a similar timeframe as those in place for influenza. Whether certain high-risk individuals may need more than one COVID-19 vaccine booster dose each year will depend on factors like vaccine durability against severe illness and levels of year-round disease activity.

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.

Incidence, Attributable Mortality, and Healthcare and Out-of-Pocket Costs of Clostridioides difficile Infection in US Medicare Advantage Enrollees.

BACKGROUND: US attributable Clostridioides difficile infection (CDI) mortality and cost data are primarily from Medicare fee-for-service populations, and little is known about Medicare Advantage Enrollees (MAEs). This study evaluated CDI incidence among MAEs from 2012 to 2019 and determined attributable mortality and costs by comparing MAEs with and without CDI occurring in 2018. METHODS: This retrospective cohort study assessed CDI incidence and associated mortality and costs for eligible MAEs ≥65 years of age using the de-identified Optum Clinformatics Data Mart database (Optum; Eden Prairie, Minnesota, USA). Outcomes included mortality, healthcare utilization, and costs, which were assessed via a propensity score-matched cohort using 2018 as the index year. Outcome analyses were stratified by infection acquisition and hospitalization status. RESULTS: From 2012 to 2019, overall annual CDI incidence declined from 609 to 442 per 100 000 person-years. Although the incidence of healthcare-associated CDI declined overall (2012, 53.2%; 2019, 47.2%), community-associated CDI increased (2012, 46.8%; 2019, 52.8%). The 1-year attributable mortality was 7.9% (CDI cases, 26.3%; non-CDI controls, 18.4%). At the 2-month follow-up, CDI-associated excess mean total healthcare and out-of-pocket costs were $13 476 and $396, respectively. Total excess mean healthcare costs were greater among hospitalized (healthcare-associated, $28 762; community-associated, $28 330) than nonhospitalized CDI patients ($5704 and $2320, respectively), whereas total excess mean out-of-pocket cost was highest among community-associated hospitalized CDI patients ($970). CONCLUSIONS: CDI represents an important public health burden in the MAE population. Preventive strategies and treatments are needed to improve outcomes and reduce costs for healthcare systems and this growing population of older US adults.

Coronavirus Disease 2019 Severity and Risk of Subsequent Cardiovascular Events.

BACKGROUND: Little is known about the relationship between coronavirus disease 2019 (COVID-19) severity and subsequent risk of experiencing a cardiovascular event (CVE) after COVID-19 recovery. We evaluated this relationship in a large cohort of United States adults. METHODS: Using a claims database, we performed a retrospective cohort study of adults diagnosed with COVID-19 between 1 April 2020 and 31 May 2021. We evaluated the association between COVID-19 severity and risk of CVE >30 days after COVID-19 diagnosis using inverse probability of treatment-weighted competing risks regression. Severity was based on level of care required for COVID-19 treatment: intensive care unit (ICU) admission, non-ICU hospitalization, or outpatient care only. RESULTS: A total of 1 357 518 COVID-19 patients were included (2% ICU, 3% non-ICU hospitalization, and 95% outpatient only). Compared to outpatients, there was an increased risk of any CVE for patients requiring ICU admission (adjusted hazard ratio [aHR], 1.80 [95% confidence interval {CI}, 1.71-1.89]) or non-ICU hospitalization (aHR, 1.28 [95% CI, 1.24-1.33]). Risk of subsequent hospitalization for CVE was even higher (aHRs, 3.47 [95% CI, 3.20-3.76] for ICU and 1.96 [95% CI, 1.85-2.09] for non-ICU hospitalized vs outpatient only). CONCLUSIONS: COVID-19 patients hospitalized or requiring critical care had a significantly higher risk of experiencing and being hospitalized for post-COVID-19 CVE than patients with milder COVID-19 who were managed solely in the outpatient setting, even after adjusting for differences between these groups. These findings underscore the continued importance of preventing severe acute respiratory syndrome coronavirus 2 infection from progressing to severe illness to reduce potential long-term cardiovascular complications.

Estimated BNT162b2 Vaccine Effectiveness Against Infection With Delta and Omicron Variants Among US Children 5 to 11 Years of Age.

Importance: Data describing the vaccine effectiveness (VE) and durability of BNT162b2 among children 5 to 11 years of age are needed. Objective: To estimate BNT162b2 VE against SARS-CoV-2 infection among children aged 5 to 11 years during Delta and Omicron variant-predominant periods and to further assess VE according to prior SARS-CoV-2 infection status and by sublineage during the Omicron variant-predominant period. Design, Setting, and Participants: This test-negative case-control study was conducted from November 2 to December 9, 2021 (Delta variant), and from January 16 to September 30, 2022 (Omicron variant), among 160 002 children tested at a large national US retail pharmacy chain, for SARS-CoV-2 via polymerase chain reaction (PCR); 62 719 children were tested during the Delta period, and 97 283 were tested during the Omicron period. Exposure: Vaccination with BNT162b2 before SARS-CoV-2 testing vs no vaccination. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infection confirmed by PCR (regardless of the presence of symptoms), and the secondary outcome was confirmed symptomatic infection. Adjusted estimated VE was calculated from multilevel logistic regression models. Results: A total of 39 117 children tested positive and 131 686 tested negative for SARS-CoV-2 (total, 170 803; 84 487 [49%] were boys; mean [SD] age was 9 [2] years; 74 236 [43%] were White non-Hispanic or non-Latino; and 37 318 [22%] were Hispanic or Latino). Final VE analyses included 160 002 children without SARS-CoV-2 infection less than 90 days prior. The VE of 2 doses of BNT162b2 against Delta was 85% (95% CI, 80%-89%; median follow-up, 1 month) compared with the Omicron period (20% [95% CI, 17%-23%]; median follow-up, 4 months). The adjusted VE of 2 doses against Omicron at less than 3 months was 39% (95% CI, 36%-42%), and at 3 months or more, it was -1% (95% CI, -6% to 3%). Protection against Omicron was higher among children with vs without infection 90 days or more prior but decreased in all children approximately 3 months after the second dose (58% [95% CI, 49%-66%] with infection vs 37% [95% CI, 34%-41%] without infection at <3 months; 27% [95% CI, 17%-35%] with infection vs -7% [95% CI, -12% to -1%] at ≥3 months without infection). The VE of 2 doses of BNT162b2 at less than 3 months by Omicron sublineage was 40% (95% CI, 36%-43%) for BA.1, 32% (95% CI, 21%-41%) for BA.2/BA.2.12.1, and 50% (95% CI, 37%-60%) for BA.4/BA.5. After 3 months or more, VE was nonsignificant for BA.2/BA.2.12.1 and BA.4/BA.5. The VE of a booster dose was 55% (95% CI, 50%-60%) against Omicron, with no evidence of waning at 3 months or more. Conclusions and Relevance: This study suggests that, among children aged 5 to 11 years, 2 doses of BNT162b2 provided modest short-term protection against Omicron infection that was higher for those with prior infection; however, VE waned after approximately 3 months in all children. A booster dose restored protection against Omicron and was maintained for at least 3 months. These findings highlight the continued importance of booster vaccination regardless of history of prior COVID-19.

PCV13 Pediatric Routine Schedule Completion and Adherence Before and During the COVID-19 Pandemic in the United States.

INTRODUCTION: A 13-valent pneumococcal conjugate vaccine (PCV13) was licensed to protect against emerging Streptococcus pneumoniae serotypes. Healthcare services, including routine childhood immunizations, were disrupted as a result of coronavirus disease 2019 (COVID-19). This study compared PCV13 routine vaccination completion and adherence among US infants before and during the COVID-19 pandemic and the relationship between primary and booster dose completion and adherence. METHODS: Retrospective data from Optum's de-identified Clinformatics® Data Mart were used to create three cohorts using data collected between January 2017 and December 2020: cohort 1 (C1), pre-COVID; cohort 2 (C2), cross-COVID; and cohort 3 (C3), during COVID. Study endpoints were completion and adherence to the primary PCV13 series (analyzed using univariate logistic regression) and completion of and adherence to the booster dose (analyzed descriptively). RESULTS: The analysis included 142,853 infants in C1, 27,211 infants in C2, and 53,306 infants in C3. Among infants with at least 8 months of follow-up from birth, three-primary-dose completion (receipt of all three doses within 8 months after birth) and adherence (receipt of doses at recommended times) were significantly higher before (C1 and C2) versus during (C3) COVID-19 (odds ratio [OR] 1.12 [95% confidence interval [CI] 1.07, 1.16] and OR 1.10 [95% CI 1.05, 1.15], respectively). A significantly higher percentage of infants received a booster dose before versus during COVID-19 (83.2% vs. 80.2%; OR 1.23; 95% CI 1.17, 1.29); similarly, booster dose adherence was higher before than during COVID-19 (51.2% vs. 47.4%; OR 1.17; 95% CI 1.13, 1.21). The odds of booster dose completion were 8.26 (95% CI 7.92, 8.60) and 7.90 (95% CI 7.14, 8.74) times as likely in infants who completed all three primary doses than in infants who did not complete primary doses before COVID-19 and during COVID-19, respectively. CONCLUSIONS: PCV13 full completion was lower during the COVID-19 pandemic compared with pre-pandemic (79.0% vs. 77.1%).