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.

Correction to 'Individual-based model of juvenile eel movement parametrized with computational fluid dynamics derived flow fields informs improved fish pass design'.

[This corrects the article DOI: 10.1098/rsos.191505.].

Individual-based model of juvenile eel movement parametrized with computational fluid dynamics-derived flow fields informs improved fish pass design.

European eel populations have declined markedly in recent decades, caused in part by in-stream barriers, such as weirs and pumping stations, which disrupt the upstream migration of juvenile eels, or elvers, into rivers. Eel passes, narrow sloping channels lined with substrata that enable elvers to ascend, are one way to mitigate against these barriers. Currently, studded eel tiles are a popular substrate. This study is the first to evaluate the flow fields within studded eel tiles and to model the swimming performance of elvers using cellular automata (CA) and individual- (or agent-) based models. Velocities and flow depths predicted by a computational fluid dynamics model of studded eel tiles are first validated against published values for a single installation angle-discharge combination. The validated model is then used to compute three-dimensional flow fields for eel passes at five different installation angles and three inflow discharges. CA and individual-based models are employed to assess upstream passage efficiency for a range of elver sizes. The individual-based model approximates measured passage efficiencies better than the CA model. Passage efficiency is greatest for shallow slopes, low discharges and large elvers. Results are synthesized into an easy-to-understand graphic to help practitioners improve eel pass designs.

Patient sex and quality of ED care for patients with myocardial infarction.

OBJECTIVE: The aim of the study was to assess the quality of care between male and female emergency department (ED) patients with acute myocardial infarction (AMI). METHODS: A 2-year retrospective cohort study of 2215 patients with AMI presenting immediately to 5 EDs from July 1, 2000, through June 30, 2002 was conducted. Data on patient characteristics, clinical presentation, and ED processes of care were obtained from chart and electrocardiogram reviews. Multivariable regression models were used to assess the independent association between sex and the ED administration of aspirin, beta-blockers, and reperfusion therapy to eligible patients with AMI. RESULTS: There were 849 women and 1366 men in the study. Female patients were older than male patients (74.3 years for women vs 66.8 years for men, P < .001). Among ideal patients, women were less likely than men to receive aspirin (76.3% of women vs 81.3% of men, P < .01), beta-blockers (51.7% of women vs 61.4% of men, P < .01), and reperfusion therapy (64.0% of women vs 72.8% of men, P < .05). However, after adjustment for age, there was no longer a significant relationship between sex and the use of aspirin (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.95-1.03), beta-blockers (OR, 0.94; 95% CI, 0.82-1.04), or reperfusion therapy (OR, 1.01; 95% CI, 0.89-1.09). In models adjusting for additional demographic, clinical, and hospital characteristics, there remained no association between sex and the processes of care. CONCLUSION: Women with AMI treated in the ED have a lower likelihood of receiving aspirin, beta-blocker, and reperfusion therapy. However, this association appears to be explained by the age difference between men and women with AMI. Although there are no apparent sex disparities in care, ED AMI management remains suboptimal for both sexes.

Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1.

Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission.

Humanized mice mount specific adaptive and innate immune responses to EBV and TSST-1.

Here we show that transplantation of autologous human hematopoietic fetal liver CD34+ cells into NOD/SCID mice previously implanted with human fetal thymic and liver tissues results in long-term, systemic human T-cell homeostasis. In addition, these mice show systemic repopulation with human B cells, monocytes and macrophages, and dendritic cells (DCs). T cells in these mice generate human major histocompatibility complex class I- and class II-restricted adaptive immune responses to Epstein-Barr virus (EBV) infection and are activated by human DCs to mount a potent T-cell immune response to superantigens. Administration of the superantigen toxic shock syndrome toxin 1 (TSST-1) results in the specific systemic expansion of human Vbeta2+ T cells, release of human proinflammatory cytokines and localized, specific activation and maturation of human CD11c+ dendritic cells. This represents the first demonstration of long-term systemic human T-cell reconstitution in vivo allowing for the manifestation of the differential response by human DCs to TSST-1.

Older emergency department patients with acute myocardial infarction receive lower quality of care than younger patients.

STUDY OBJECTIVE: We assessed the independent relationship between age and the quality of medical care provided to patients presenting to the emergency department (ED) with acute myocardial infarction. METHODS: We conducted a 2-year retrospective cohort study of 2,216 acute myocardial infarction patients presenting urgently to 5 EDs in Colorado and California from July 1, 2000, through June 30, 2002. Data on patient characteristics, clinical presentation, and ED processes of care were obtained from the ED record and ECG review. Patients were divided into 6 groups based on their age at the time of their ED visit: younger than 50 years, 50 to 59 years, 60 to 69 years, 70 to 79 years, 80 to 89 years, and 90 years or older. Hierarchic multivariable regression was used to assess the independent association between age and the provision of aspirin, beta-blockers, and reperfusion therapy (fibrinolytic agent or percutaneous coronary intervention) in the ED to eligible acute myocardial infarction patients. RESULTS: Of ideal candidates for treatment in the ED, 1,639 (80.5%) of 2,036 received aspirin, 552 (60.3%) of 916 received beta-blockers, and 358 (77.8%) of 460 received acute reperfusion therapy. After adjustment for demographic, medical history, and clinical factors, older patients were less likely to receive aspirin (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.77 to 0.93), beta-blockers (OR 0.79, 95% CI 0.71 to 0.88), and reperfusion therapy (OR 0.30, 95% CI 0.18 to 0.52). CONCLUSION: Older patients presenting to the ED with acute myocardial infarction receive lower-quality medical care than younger patients. Further investigation to identify the reasons for this disparity and to intervene to reduce gaps in care quality will likely lead to improved outcomes for older acute myocardial infarction patients.

Development and activation of human dendritic cells in vivo in a xenograft model of human hematopoiesis.

Dendritic cells (DCs) are derived from CD34+ progenitors and play a central role in the development of immune responses and in tolerance. Their therapeutic potential underscores the need for in vivo models that accurately recapitulate human DC development and function to provide a better understanding of DC biology in health and disease. Using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human CD34+ cells as a model of human hematopoiesis, we examined DC ontogeny. Progenitors of both myeloid (m) and plasmacytoid (p) DCs were identified in the bone marrow of mice up to 24 weeks after transplant, indicating ongoing and sustained production of DCs after initial engraftment. To determine whether human DCs derived from transplanted stem cells were functional, their response to acute inflammation using lipopolysaccharide (LPS) was examined. Eighteen hours after LPS administration, a dramatic increase in the plasma levels of the human inflammatory cytokines interleukin (IL)-8, IL-10, tumor necrosis factor-alpha, and IL-12p70 was observed. Only mDCs and not pDCs responded in vivo to LPS by upregulating CD86 and CD83. In vivo activation of human mDCs resulted in a substantial increase in the ability of mDCs to induce the proliferation of naive human T cells. Taken together, these data indicate that human CD34+ cells seem to have differentiated appropriately within the NOD/SCID microenvironment into DCs that are developmentally, phenotypically, and functionally similar to the DC subsets found in humans.

Experimental infection of NOD/SCID mice reconstituted with human CD34+ cells with Epstein-Barr virus.

Epstein-Barr virus (EBV)-induced lymphoproliferative disease is an important complication in the context of immune deficiency. Impaired T-cell immunity allows the outgrowth of transformed cells with the subsequent production of predominantly B-cell lymphomas. Currently there is no in vivo model that can adequately recapitulate EBV infection and its association with B-cell lymphomas. NOD/SCID mice engrafted with human CD34(+) cells and reconstituted mainly with human B lymphocytes may serve as a useful xenograft model to study EBV infection and pathogenesis. We therefore infected reconstituted mice with EBV. High levels of viral DNA were detected in the peripheral blood of all infected mice. All infected mice lost weight and showed decreased activity levels. Infected mice presented large visible tumors in multiple organs, most prominently in the spleen. These tumors stained positive for human CD79a, CD20, CD30, and EBV-encoded RNAs and were light chain restricted. Their characterization is consistent with that of large cell immunoblastic lymphoma. In addition, tumor cells expressed EBNA1, LMP1, and LMP2a mRNAs, which is consistent with a type II latency program. EBV(+) lymphoblastoid cell lines expressing human CD45, CD19, CD21, CD23, CD5, and CD30 were readily established from the bone marrow and spleens of infected animals. Finally, we also demonstrate that infection with an enhanced green fluorescent protein (EGFP)-tagged virus can be monitored by the detection of infected EGFP(+) cells and EGFP(+) tumors. These data demonstrate that NOD/SCID mice that are reconstituted with human CD34(+) cells are susceptible to infection by EBV and accurately recapitulate important aspects of EBV pathogenesis.

Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors.

Distinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develop human myeloid and plasmacytoid DCs. The skin displays immature DCs expressing Langerin, while other tissues display interstitial DCs. Myeloid DCs from these mice induce proliferation of allogeneic CD4 T cells in vitro, and bone marrow human cells containing plasmacytoid DCs release interferon-alpha (IFN-alpha) upon influenza virus exposure. Injection of influenza virus into reconstituted mice triggers IFN-alpha release and maturation of mDCs. Thus, these mice may provide a model to study the pathophysiology of human DC subsets.