The Value-Based Price for a Bivalent COVID-19 Booster Vaccine in the United Kingdom

Objectives: The United Kingdom (UK) implemented an autumn 2022 booster programme that allowed those at higher risk from COVID-19, including those >= 50 years, to receive a booster to increase protection against infection and subsequent severe outcomes. As the UK transitions out of the pandemic, future booster campaigns may be required to maintain protection against such outcomes. The objective of this analysis was to estimate the value-based price (VBP) for a bivalent COVID-19 vaccine used in a future autumn 2023 campaign in the UK to protect people aged >= 50 years. Method(s): A Susceptible-Exposed-Infected-Recovered (SEIR) model was used to predict infections across a 1-year time horizon starting September 2023 with and without an autumn booster campaign. Initial effectiveness was predicted to be 89% and 97% against infection and hospitalization respectively based on BA.4/BA.5 antibody titers and correlates of protection. A monthly decline in protection of 1.4% and 4.8%, respectively, was assumed based on monovalent vaccine data. A decision tree was used to predict the quality-adjusted life-years (QALY) lost and costs associated with infections. Result(s): Considering a willingness-to-pay (WTP) threshold of 20,000/QALY, the VBP associated with an autumn 2023 booster campaign is 343/dose. Considering a WTP threshold of 30,000, the VBP increases to 476. In sensitivity analyses, excluding the post-infection costs (e.g., long COVID), reduces the VBP by 11%. Varying the hospitalization rates by +/-25% changes the VBP by +/- 6%. Varying hospitalization unit costs only impacts the VBP by 1%. Doubling the rate of waning for booster effectiveness increases the VBP by 54% because the effectiveness provided from past campaigns falls faster and an autumn 2023 booster becomes more valuable. Conclusion(s): While the trajectory of COVID-19 incidence is highly uncertain, pricing the bivalent booster lower than the VBP is expected to result in a cost-effective strategy for the UK.Copyright © 2023

Teleconsultation in respiratory medicine - A position paper of the Portuguese Pulmonology Society.

The COVID-19 pandemic crisis, among so many social, economic and health problems, also brought new opportunities. The potential of telemedicine to improve health outcomes had already been recognised in the last decades, but the pandemic crisis has accelerated the digital revolution. In 2020, a rapid increase in the use of remote consultations occurred due to the need to reduce attendance and overcrowding in outpatient clinics. However, the benefit of their use extends beyond the pandemic crisis, as an important tool to improve both the efficiency and capacity of future healthcare systems. This article reviews the literature regarding telemedicine and teleconsultation standards and recommendations, collects opinions of Portuguese experts in respiratory medicine and provides guidance in teleconsultation practices for Pulmonologists.

Evaluation of a heterologous booster vaccine regimen: Pfizer-BioNTech BNT162b2 mRNA booster vaccine following priming with Novavax NVX-CoV2373

Background. In the United States, booster vaccines for persons 18 years and older were approved under Emergency Use Authorization (EUA) in September 2021. Waning immunity following SARS-CoV-2 primary vaccination series led to recommendations for booster vaccination. Emerging data suggest that providing boosters different from the primary series (heterologous vaccination) may provide a broader immune response than boosting with the same vaccine (homologous vaccination). CDC recommended the Pfizer-BioNTech BNT162b2 30-mug mRNA booster vaccine to clinical trial participants >6 months post study vaccines if not planned for boosting within the study. Methods. We conducted an observational study of persons who received 2 doses of Novavax protein-based NVX-CoV2373 vaccine 21 days apart, in a Phase 3 clinical trial, and subsequently received a Pfizer BNT162b2 booster vaccine under EUA. Serologic assays, including the Roche anti-nucleocapsid (N) IgG and anti-Spike (S) IgG, were performed on blood collected pre-booster (D0) and on days 18 (D18) and 34 (D34) post-booster vaccine. The anti-S IgG geometric means (GMTs) were calculated over study time points. Wilcoxon signed rank test was performed to compare anti-S IgG response between D0 and D18 and D0 and D34. Results. Of 26 participants enrolled, 16 (57%) were women;the median age was 47 years (range 29-67). Roche anti-N antibodies were negative at all visits. Time from second NVX-CoV2373 vaccine to Pfizer BNT162b2 booster was a median of 10.4 months in 54% of participants and 7 months in 46% of participants. Anti-S IgG GMTs were 222 BAU/ml D0, 24,723 BAU/ml D18, and 24,584 BAU/ml D34 (p< 0.0001 for comparisons of D0 with D18 & D34). Overall, participants tolerated the booster vaccine without significant adverse events. Cell mediated immunity and D614G pseudovirus neutralizing antibody assays are in progress. Figure 1. Anti-S IgG titers pre and post-booster vaccine 16 participants included with all 3-time study time points for comparison. Conclusion. Two doses of NVX-CoV2373 vaccine followed by the Pfizer BNT162b2 booster vaccine resulted in ~100-fold increase in anti-S IgG against SARS-CoV-2. No participant had evidence of prior SARS-CoV-2 infection by anti-N IgG. Two doses of NVX-CoV2373 vaccine followed by one dose of Pfizer BNT162b2 vaccine is an effective and well-tolerated regimen for boosting anti-S IgG against SARS-CoV-2.

High incidence of obstructive sleep apnea in long COVID-19 patients

Introduction: There is a physiological plausibility for obstructive sleep apnoea (OSA) being a factor to long COVID-19 symptoms: OSA activates the renin-angiotensin-aldosterone system and angiotensinconverting enzyme 2, which is the entry receptor SARS-CoV-2 in the cells. The aim of this study is to identify the incidence of obstructive sleep apnea in long COVID-19 patients. Method(s): Observational cohort, cross-sectional study of post- COVID-19 symptomatic patients, admitted in the out patient post COVID-19 clinic in Portimao Hospital (Portugal), from july 2021 to december 2021. Inclusion criteria: >=18 years;previous COVID-19 at least six months before the initial study protocol evaluation, confirmed by a positive real-time reverse-transcription polymerase chain reaction on a nasopharyngeal swab.;persistent symptoms after cure criteria defined by WHO. Exclusion criteria: Patients who had a concomitant neurological disorder;patients who were on invasive mechanical ventilation and patients with persistent fatigue symptoms in the 6 months before SARS-CoV 2 infection. The OSA diagnosis was assessed using portable monitoring device type III (in-home polygraphy), between the 6-7th months after the diagnosis of COVID-19. The OSA severity was performed using the American Academy of Sleep Medicine scoring criteria. Result(s): A total of 88 patients attended the post-COVID-19 consultation, 24 patients meet the exclusion criteria and 64 patients were enrolled: 28,1% (18) had mild COVID-19, 17,2% (11) moderate and 54,7% (35) severe acute disease. The average age was 56 years, the BMI was 29 Kg/m2 and 56% were men. We found a OSA incidence of 75% (48). The distribution of OSA severity was: 50% (24) mild, 29% (14) moderate and 21% (10) severe. In this group of post COVID-19 patients with OSA, the median age and BMI was the same of the total enrolled patients, and 58% were men. Conclusion(s): There is a high incidence of OSA, in long COVID-19 patients. The knowledge of this risk is essential to establish the follow up and investigation protocol for postcovid-19 patients.

A systematic review of whether COVID-19 randomized controlled trials reported on demographic and clinical characteristics.

PURPOSE: We aim to assess the reporting of key patient-level demographic and clinical characteristics among COVID-19 related randomized controlled trials (RCTs). METHODS: We queried English-language articles from PubMed, Web of Science, clinicaltrials.gov, and the CDC library of gray literature databases using keywords of "coronavirus," "covid," "clinical trial" and "randomized controlled trial" from January 2020 to June 2021. From the search, we conducted an initial review to rule-out duplicate entries, identify those that met inclusion criteria (i.e., had results), and exclude those that did not meet the definition of an RCT. Lastly, we abstracted the demographic and clinical characteristics reported on within each RCT. RESULTS: From the initial 43 627 manuscripts, our final eligible manuscripts consisted of 149 RCTs described in 137 articles. Most of the RCTs (113/149) studied potential treatments, while fewer studied vaccines (29), prophylaxis strategies (5), and interventions to prevent transmission among those infected (2). Study populations ranged from 10 to 38 206 participants (median = 100, IQR: 60-300). All 149 RCTs reported on age, 147 on sex, 50 on race, and 110 on the prevalence of at least one comorbidity. No RCTs reported on income, urban versus rural residence, or other indicators of socioeconomic status (SES). CONCLUSIONS: Limited reporting on race and other markers of SES make it difficult to draw conclusions about specific external target populations without making strong assumptions that treatment effects are homogenous. These findings highlight the need for more robust reporting on the clinical and demographic profiles of patients enrolled in COVID-19 related RCTs.

The impact of COVID-19 restrictions on perceived health and wellbeing of adult Australian sport and physical activity participants.

Individuals' access to sport and physical activity has been hampered due to COVID-19 lockdown restrictions. In Australia participation in community sport was cancelled during lockdowns. There is limited research on the impact of sport participation restrictions on the health and wellbeing of adults.AimThe aim of this study was to investigate the perceived health and wellbeing of a sample of predominantly active Australian adults, both during COVID-19 and in comparison with one year earlier (pre COVID-19).MethodsA survey was conducted during the first COVID-19 restrictions and lockdowns in Australia in May-June 2020. It was distributed by national and state sporting organisations and through researchers' social media accounts. This particular paper focuses on adults aged 18-59 years. The survey collected information on participant demographics, the sport and physical activity patterns pre- COVID-19, and health and wellbeing outcomes during COVID-19 lockdown and compared to one year earlier. The health measures were cross-tabulated against the demographic and sport and physical activity variables, and group profiles compared with chi-square tests. Scales were derived from three wellbeing questions, and group differences were analysed by t-tests and F-tests.ResultsThe survey sample included 1279 men and 868 women aged 18-59 years. Most (67%) resided in metropolitan cities. The great majority (83%) were sport participants. During COVID-19 lockdown men were significantly more likely than women to report worse or much worse general (p = 0.014), physical (p = 0.015) and mental health (p = 0.038) and lower life satisfaction (p = 0.016). The inactive adults were significantly more likely to report poorer general health (p = 0.001) and physical health (p = 0.001) compared to active adults. The younger age cohort (18-29 years) were significantly more likely to report poorer general wellbeing (p < 0.001), and lower life satisfaction (p < 0.001) compared to the older age groups.ConclusionIt seems that the absence of playing competitive sport and training with friends, teams and within clubs has severely impacted males and younger adults in particular. Sports clubs provide an important setting for individuals' health and wellbeing which is why clubs require the capacity to deliver sport and individuals may need to regain the motivation to return.

Rationale and design of the Prone Position and Respiratory Outcomes in Non-intubated COVID-19 PatiEnts: The "PRONE" Study.

While benefits of prone position in mechanically-ventilated patients have been well-described, a randomized-control trial to determine the effects of prone positioning in awake, spontaneously-breathing patients with an acute pneumonia has not been previously conducted. Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts: the "PRONE" Study (PRONE) was conducted in non-intubated hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia as defined by respiratory rate ≥ 20/min or an oxyhemoglobin saturation (SpO2) ≤ 93% without supplemental oxygen [1]. The PRONE trial was designed to investigate the effects of prone positioning on need for escalation in respiratory support, as defined by need for transition to a higher acuity level of care, increased fraction of inspired oxygen (FiO2), or the initiation of invasive mechanical ventilation. Secondary objectives were to assess the duration of effect of prone positioning on respiratory parameters such as respiratory rate and SpO2, as well as other outcomes such as time to discharge or transition in level of care.

Implementation of a home monitoring system for COPD patients during the SARS-CoV-2 pandemic: A feasibility study

RATIONALE: Remote monitoring of COPD patients has the potential to improve clinical outcomes. The ability to successfully deploy home monitoring technologies to COPD patients remotely without in-person encounters is of particular interest during the SARS-CoV-2 pandemic. We present interim results from a prospective implementation study of a home monitoring system in COPD patients at-risk for frequent acute exacerbations of COPD (AECOPD). METHODS: We recruited non-hospitalized individuals aged 40-80 years with spirometryconfirmed COPD and increased AECOPD risk (one hospitalization or two outpatient AECOPD in the prior year). The home system includes: a GoHome™ Data Collection Platform and GoSpiro® spirometer (Monitored Therapeutics, Dublin, OH), and a 3230 pulse oximeter (Nonin Medical, Plymouth, MN). The tablet-based GoHome™ has an auto-start system requiring no computer skills for operation. Eligible participants were contacted via phone, and if interested, were sent a participation kit containing informed consent and the home system. After remotely collecting ICF, participants completed device setup and baseline spirometry using Avatar coaching. At set times, the device collects responses for an automated COPD Action Plan and displays reminders for the patient to use the integrated Bluetooth® spirometer and pulse oximeter. The GoSpiro® measures slow vital capacity (SVC) and forced vital capacity (FVC) using an Avatar-assisted technology coach on the GoHome™ (Figure). The Avatar coaches the patient through each measurement following ATS recommendations for instructions and coaching, followed by error identification and maneuver error correction without human intervention. Patients are engaged daily with the COPD Action Plan. Automated scores return immediate patient guidance along with appropriate clinician alerts. Results are cellular or Wi-Fi uploaded to a cloud server for realtime investigator review. Following demonstrated proficiency, daily measurements of spirometry (FVC Tuesday/Thursday, SVC all other days), daily pulse oximetry and COPD Action Plan were performed. Participant study duration was three months. RESULTS: To date, seven of 12 planned participants have been enrolled. All enrolled participants have successfully activated all device components and performed FVC maneuvers meeting ATS acceptability standards. All participants were able to complete collection and transmission of daily pulse oximetry and COPD Action Plan data. One participant requested study withdrawal after three weeks and six participants remain on study. CONCLUSIONS: Deployment of a COPD home telemonitoring system platform including daily spirometry, pulse oximetry and electronic questionnaire without in-person contact is feasible. This technology may be useful in settings where in-person visits are not feasible due to patient safety, remote location or access-related issues. .

Learner Driven Call Center to increase Convalescent Plasma Donation in COVID-19

Background. Convalescent plasma (CP) may be obtained from patients who have recovered from the novel coronavirus disease, COVID-19, caused by the virus SARS-CoV-2. Although not FDA approved, preliminary data suggests patients who receive convalescent plasma from recovered donors may have shortened recovery time and symptom reduction. The purpose of the study is to detail learner recruitment of convalescent plasma donation (CPD) for treating hospitalized COVID-19 patients. Methods. Prisma Health Midlands formed a multidisciplinary CP donation team, consisting of seven COVID-19-certified pharmacy learner volunteers, two pharmacists, and two providers. Primary eligibility criteria were SARS-CoV-2 polymerase chain reaction (PCR) positivity at least 28 days prior to donation and asymptomatic for a minimum of 14 days. Donors were excluded based on FDA guidelines for CPD, limiting ineligible contact. Team learners were trained on call techniques and subsequently contacted, educated, and requested candidates donate through this program. Willing donors were then linked to The Blood Connection to circulate CP back into the Prisma Health System, creating a self-sustaining and closed-loop donation cycle. Results. In total, 253 recovered adult patients with positive SARS-CoV-2 PCR test results were evaluated. 195 patients met baseline inclusion criteria for contact. This pre-screen reduced call and travel time for ineligible candidates. 108 patients were successfully reached. Of the 108, n=79 (73.14%) accepted referral to The Blood Connection, and n=29 (26.85%) were no longer candidates primarily due to patient communicated new exclusionary factors, such as active COVID-19 symptoms. The program allowed for rapid, internal access to CP for patients hospitalized with COVID-19 at Prisma Health Midlands. Conclusion. Interest and awareness in COVID-19 CPD was successfully increased upon direct communication from the team and was felt to represent a personnel intense but successful model for recruiting potential CP donors. This program educated and utilized learners during this pandemic to enhance Prisma Health's ability to obtain CP for hospitalized patients using a closed system.

Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. METHODS: We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. RESULTS: The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. CONCLUSION: Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.

Understanding the impact of COVID-19 on youth sport in Australia and consequences for future participation and retention.

BACKGROUND: COVID-19 continues to represent the single biggest challenge to contemporary community sport globally. Compliance with social distancing policies, strict return-to-play protocols, and COVID-19 specific training has, perhaps, forever changed the way that children and young people engage in organised sport. Within this context, and while many children and families seek to re-engage with community sport, we (researchers and sport practitioners) have an obligation to ask questions about how the pandemic has impacted youth sport, understand the short- and long-term consequences, and explore what (if any) opportunities can be seized to assist and improve future participation and retention. The aim of this paper was to present an in-depth exploration of the impact of COVID-19 on youth sport in South Australia. METHODS: Within an interpretive descriptive methodology, this qualitative investigation draws on rich, individual interview and focus group data with 39 youth (ages 15-18), parents, coaches, and sport administrators. A reflexive thematic analysis was undertaken, leading to the development of four substantive themes. RESULTS: We conceptualised the '4 Rs' to advance theoretical understandings about the pandemic's impact on youth sport, including the themes 'recognising struggle', 'reconnection', 're-engaging after restrictions, and 'reimagining sport'. The themes captured insights about a decline in mental wellbeing and physical activity, an increase in family connectedness, the challenge for sports to attract volunteers and participants back into sport, and the opportunities to reset values and philosophies underpinning the provision of youth sport. CONCLUSION: The findings provide valuable insight into the youth sport setting as a result of the global pandemic and suggest that families, sporting clubs and sporting organisations require additional resources and tools (for example, support for parents to facilitate their children's training at home during lockdown) to aid recovery efforts and to ensure the survival and prosperity of youth sport into the future.