Vaccine-Preventable Hospitalisations from Seasonal Respiratory Diseases: What Is Their True Value?

Hospitals in England experience extremely high levels of bed occupancy in the winter. In these circumstances, vaccine-preventable hospitalisations due to seasonal respiratory infections have a high cost because of the missed opportunity to treat other patients on the waiting list. This paper estimates the number of hospitalisations that current vaccines against influenza, pneumococcal disease (PD), COVID-19, and a hypothetical Respiratory Syncytial Virus (RSV) vaccine, could prevent in the winter among older adults in England. Their costs were quantified using a conventional reference costing method and a novel opportunity costing approach considering the net monetary benefit (NMB) obtained from alternative uses of the hospital beds freed-up by vaccines. The influenza, PD and RSV vaccines could collectively prevent 72,813 bed days and save over £45 million in hospitalisation costs. The COVID-19 vaccine could prevent over 2 million bed days and save £1.3 billion. However, the value of hospital beds freed up by vaccination is likely to be 1.1-2 times larger (£48-93 million for flu, PD and RSV; £1.4-2.8 billion for COVID-19) when quantified in opportunity cost terms. Considering opportunity costs is key to ensuring maximum value is obtained from preventative budgets, as reference costing may significantly underestimate the true value of vaccines.

Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic.

BACKGROUND: Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented. AIM: To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients. METHODS: A systematic literature search on PubMed was carried out until June 21, 2022. RESULTS: A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree. CONCLUSION: To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.

Recognising The Broader Value Of Vaccines In Health Technology Assessment: Worth A Shot?

IntroductionThe COVID-19 pandemic shows that the impact of effective vaccines extends well beyond vaccinated individuals and healthcare systems. Yet, these externalities are not typically considered in health technology assessments (HTA) which may underestimate vaccines’ broader value. We explored to what extent future vaccines relevant to England might exhibit such broader value.MethodsWe compared the ten value elements of an existing vaccine evaluation framework to the value elements considered in England according to the Joint Committee on Vaccine and Immunisation (JCVI) and the National Institute for Health and Care Excellence's (NICE) guidelines. Using literature and expert opinion we then explored, for a selection of ten vaccines with an expected UK-launch within five years, on which value elements each vaccine might potentially show added value.ResultsUp to five of ten value elements are unlikely to be considered by JCVI or NICE, including patient and carer productivity, enablement value, impact on antimicrobial resistance and transmission value. Of vaccines studied, 100 percent will potentially generate value on at least one broader value element that is currently ignored;60 percent to 80 percent may increase vaccinee/patient or carer productivity respectively.ConclusionsThere is a substantial gap between value generation and value recognition of vaccines in HTA in England. This might lead to undervaluation and underutilization of vaccines, leaving societies more vulnerable than needed when faced with infectious diseases.

Towards a Broader Assessment of Value in Vaccines: The BRAVE Way Forward.

BACKGROUND: The COVID-19 pandemic shows that the impact of effective vaccines can extend well beyond vaccinated individuals and healthcare systems. Yet, these broader value elements are not typically considered in Health Technology Assessment (HTA) which may underestimate vaccines' broader value. OBJECTIVES: This study aimed to (1) describe the gap between broader value elements identified in value frameworks for vaccines and those recognised in HTA of vaccines in nine developed markets, and (2) develop expert-informed, consensus-based recommendations on how hurdles for broader value recognition could be overcome. METHODS: We used a four-step modified Delphi method consisting of literature research (phase I, pearl-growing approach using PubMed Web of Science and Google covering the years 2000-2019), two consecutive phases of expert elicitation (phase II and III, including two email surveys and one virtual round table with 10 experts from 9 countries) and synthesis of recommendations (phase IV). RESULTS: Results show that about half of the broader value elements relevant to vaccines are not (consistently) considered in HTA processes of multiple higher-income countries. Experts identified five priority areas for broader value recognition, including considering (1) more comprehensive cost offsets within the health care system, (2) carer quality of life, (3) transmission value, (4) prevention of antimicrobial resistance and (5) macroeconomic effects. CONCLUSION: To achieve a broader recognition of the value of vaccines, a three-pronged approach was recommended, focusing on (1) Evidence: proactively steering generation of high-quality evidence to quantify the broader value of vaccines to society; (2) Ability: leveraging and further developing existing methodological and analytic expertise to appropriately recognise the broad value of vaccines within HTA processes; (3) Willingness: Stimulating stakeholder engagement to change the status quo and move towards more transparent and comprehensive value assessment processes for vaccines globally.

Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1ß, IL-6, IL-15 and TNF-α.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1ß, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1ß in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.