Abstract WP400: SARS-CoV-2 Spike Protein Accelerates Alzheimer’s Disease-Related Dementia Through Increased Cerebrovascular Inflammation in hACE2 Mice

Stroke, Volume 56, Issue Suppl_1, Page AWP400-AWP400, February 1, 2025. SARS-COV-2 causes neurological and cognitive impairments and aggravates Alzheimer’s Disease-Related Dementia (ADRD). Yet, the molecular mechanism is not fully understood. We have previously shown that SARS-CoV-2 spike protein disturbs the brain’s renin-angiotensin system (RAS) and increases cerebrovascular inflammation. We hypothesize that SARS-CoV-2 spike protein will accelerate hypoxia-induced ADRD via augmenting cerebrovascular inflammation and impairing blood-brain-barrier (BBB) functions. We propose that the pharmacological restoration of the RAS balance using Losartan, an AT1receptor blocker, will improve SARS-CoV-2 spike protein-induced ADRD.Methods:Hypoxia-induced ADRD was produced in humanized ACE2 mice, a COVID-19 mouse model, using a permanent unilateral common carotid artery ligation (UCCL). Cerebral hypoxia was confirmed by laser speckle imaging. hACE-2 mice received either vehicle, SARS-CoV-2 spike protein via jugular vein, or spike protein with Losartan (10 mg/kg) in drinking water after UCCL. ADRD was assessed via Novel Object Recognition at baseline, seven days, and fourteen days after surgery. Cerebrovascular inflammatory markers and tight junction proteins (TNF-α, Il-6, VEGF, MMP-9, and occludin) were measured in brain homogenate using RT-PCR and Western Blots.Results:Blood flow analysis confirmed cerebrovascular hypoxia in all groups. Spike protein further decreased cerebral blood flow, which was prevented with Losartan (P

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Abstract WP209: Comparative Functional Outcomes for Ischemic Stroke Patients with and without COVID-19

Stroke, Volume 56, Issue Suppl_1, Page AWP209-AWP209, February 1, 2025. Background:COVID-19, primarily a respiratory illness caused by SARS-CoV-2, is associated with vascular complications like ischemia due to endothelial injury, hypercoagulability, and inflammation. This study examines how COVID-19 affects functional outcomes of ischemic stroke patients.Methods:Ischemic stroke patients admitted to our Joint Commission-certified primary stroke center were retrospectively analyzed from March 1, 2020, to March 1, 2022. A subgroup analysis was conducted for patients during the vaccination period (April 14, 2021, to March 1, 2022). Patients were included if they were ≥18 years old and had a stroke on admission or during hospitalization. Univariate and multivariable analyses were used, with a significance threshold of p

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Descriptive retrospective cross-sectional study of rehabilitation care for poststroke users in Quebec during the COVID-19 pandemic

Objectives
During the COVID-19 pandemic, designated rehabilitation centres were established in the province of Québec, where strict sociosanitary measures such as isolation and mandatory personal protection equipment requirements were followed. This study aimed to describe the impact of the pandemic on rehabilitation care indicators for poststroke users with (COV+) and without (COV–) COVID-19 infection in designated rehabilitation centres compared with those admitted in the previous year (pre-COV).

Method
A retrospective analysis of 292 medical files was performed in 3 rehabilitation centres. Demographic characteristics were collected, as well as indicators routinely collected in acute care and rehabilitation such as length of stay (LOS), the Functional Independence Measure and a number of physical/occupational therapy (PT/OT) sessions. Non-parametric statistical tests were used to compare variables among the three groups.

Results
COV+ users were older than COV– and pre-COV ones (p

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Overcoming Hepatitis B Vaccine Nonresponsiveness

Hepatitis B virus (HBV) infection continues to pose a significant global health challenge despite the availability of effective vaccines for more than 4 decades and antivirals for almost 3 decades. The World Health Organization estimates that more than 254 million people worldwide are living with chronic HBV infection; 1.2 million new infections occurred in 2022. Even though the introduction of hepatitis B vaccines has drastically reduced the incidence of new HBV infections, barriers such as limited access, low vaccine uptake, and suboptimal vaccine efficacy in specific populations such as older persons, individuals with diabetes, obesity, or current smoking, and immunocompromised persons (eg, those living with HIV or chronic kidney disease) account for the continued occurrence of new infections. These challenges necessitate public health efforts to improve access and uptake of hepatitis B vaccination and research to enhance vaccine immunogenicity.

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Herpes

To the Editor I read with great interest the recent JAMA Insights article on genital herpes. However, the authors did not mention the Tzanck smear test in the Diagnosis section. Indeed, this technique described in 1947 by Arnault Tzanck is a neglected, but rapid, reliable, and cost-effective bedside technique to establish the diagnosis of acantholytic dermatoses, such as herpes simplex virus (HSV) and varicella zoster virus infections. Gentle scraping of the base of vesiculobullous lesions (incised if intact or stripped of their crust if ulcerated) with a scalpel allows for cytologic spreading on a glass slide, air-drying, and quick Giemsa staining. Instant microscopic examination by a trained cytologist enables identification of acantholytic and multinucleated keratinocytes with typical nuclear inclusion bodies indicating diagnosis of HSV and varicella zoster virus infections in 80% to 90% of patients, respectively. However, a Tzanck smear cannot differentiate between HSV-1 and HSV-2 infections. Of note, this diagnostic test can be useful in other acantholytic dermatoses, such as pemphigus and genetic skin diseases, including Darier disease and Hailey-Hailey disease. In conclusion, the Tzanck smear test can provide an early diagnosis of mucocutaneous HSV infections and enable appropriate treatment in skilled hands. For inexperienced clinicians, artificial intelligence can be used to evaluate Tzanck smear findings with high accuracy.

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AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals

Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr. This clinical practice guideline update aims to inform frontline health care practitioners by providing evidence-based practice recommendation for the management of HBVr in at-risk individuals.

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Global vaccine research and application hotspots and trends: a systematic bibliometric analysis based on SCIE highly cited papers

Objectives
COVID-19, a public health emergency affecting the world in 2019, not only greatly promoted the development and application of vaccines but also effectively shortened the publishing time of scientific papers. In view of these facts, the current situation, status, problems and development trends of vaccine research and application were explored through bibliometric analysis of highly cited papers in the vaccine field within the time frame of 2014–2024, and the countries, institutions, authors, funding agencies and other relevant information that contributed most to vaccine research and application were summarised.

Design
Bibliometric analysis through data analysis and visual mapping.

Data sources
Scientific articles.

Data extraction and synthesis
‘Vaccine’ and ‘vaccines’ were used in the WoS database to retrieve the publications and to adequately collect the data; Microsoft Excel was used for data analysis; and VOSviewer was used for visual description of data. Overall publication trends, countries, institutions and funding agencies, authors and articles, journals and languages, and research areas and co-occurrence keywords were analysed by bibliometrics.

Results
A total of 3258 highly cited papers were published in the field of vaccines in the past decade, from 735 different journals. With the COVID-19 pandemic in 2019, the number of highly cited papers in the field of vaccine research increased significantly from 2020 to 2024, accounting for 76.12%. The number of highly cited papers for vaccines peaked in 2021 and 2022, followed by a rapid decline. Highly cited papers came from 7133 institutions in 153 countries, and the most influential country in the field of vaccines was the USA, which published 1733 highly cited papers, accounting for 53.19% of the highly cited papers. The top 15 institutions with the largest influence were all from the USA or UK with 2567 published papers in total, accounting for 78.79% of highly cited papers. 4787 funding agencies were recognised in funding 2368 highly cited papers. A total of 30 926 authors in 90 research areas contributed significantly to global vaccine research. The most highly cited paper was ‘Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine’ from the New England Journal of Medicine, which was cited 9435 times in total. Among the 9848 co-occurrence keywords, COVID-19 (including SARS-CoV-2, 2019-COVID and SARS2) was the most frequently co-occurrence keyword. It appeared in 1720 articles, accounting for 52.79%, indicating that COVID-19 was the most popular study in the last decade.

Conclusions
This study visualised the research and application of vaccines in the world from the perspective of papers output, drew the knowledge map and identified the important research hotspots and development trends in the vaccine field in the recent 10 years (2014–2024), which is helpful for Centres for Disease Control and Prevention, clinicians, researchers and health policymakers to better understand the research status and problems in vaccine research and application and predict its future development direction.

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Adaptive clinical trial of AZD7442 and SARS-CoV-2 vaccination in immunosuppressed patients highly vulnerable to infection with SARS-CoV-2 virus (RAPID-PROTECTION): protocol for a multicentre, interventional open-label, randomised controlled trial

Introduction
Despite repeated vaccinations against SARS-CoV-2 virus, patients who are immunocompromised remain at very high risk of catching SARS-CoV-2 virus and becoming unwell. AZD7442 (Evusheld) is a long-acting monoclonal antibody treatment that has been shown in clinical trials to prevent SARS-CoV-2 infection for up to a year after a single dose. Vaccines require a healthy immune system to generate protective immunity. AZD7442 may prevent SARS-CoV-2 infection in immunocompromised individuals that may not have responded to repeated vaccinations against SARS-CoV-2 virus. Unlike vaccinations, AZD7442 reaches effective levels within the body a few hours after a single dose. The RAPID-PROTECTION trial will determine the levels of immune protection that AZD7442 offers patients at the very highest risk of SARS-CoV-2 infection and whether this protection can be further enhanced by repeated vaccination against SARS-CoV-2 virus.

Methods
RAPID-PROTECTION is a multicentre, interventional and open-label adaptive platform trial that aims to recruit 350 immunocompromised participants across five UK centres. Participants will be administered AZD7442 on day 0 followed by a SARS-CoV-2 vaccination 28 days later. Participants will be randomised (1:1) to the Moderna vaccine or Pfizer/BioNTech vaccine. Participant samples will be taken at baseline and at multiple timepoints after the administration of AZD7442.

Analysis
The participant samples will be analysed to measure the function and magnitude of SARS-CoV-2 specific antibody and T-cell responses at baseline and at multiple timepoints after the administration of AZD7442. The immunological effect of the study interventions will be determined by comparison of the results of immunological assessments at baseline and subsequent timepoints.

Ethics and dissemination
The trial protocol was approved by the research ethics committee of the National Health Service (reference 22/HRA/0359), Health Research Authority and Health and Care Research Wales on 25 July 2022. Findings will be disseminated through peer-reviewed journals and presented at scientific conferences.

Trial registration number
ISRCTN53507177.

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