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Abstract 15748: Association of Clonal Hematopoiesis in the Setting of Human Immunodeficiency Virus Infection With Subclinical Atherosclerosis and Vascular Inflammation
Circulation, Volume 148, Issue Suppl_1, Page A15748-A15748, November 6, 2023. Background:Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) and common in HIV, but whether CHIP contributes to atherosclerosis in HIV is unknown. We hypothesized CHIP is associated with atherosclerosis and arterial inflammation among people with HIV (PWH).Methods:We studied treated, suppressed PWH ages 35-70 years old with ≥1 CVD risk factor. CHIP mutations were detected with a validated targeted sequencing assay. We measured carotid intima-media thickness (IMT) longitudinally with ultrasound and aortic inflammation and lymph node activity using cross-sectional18F-FDG-PET. Inflammatory biomarkers were measured with a multiplex electrochemiluminescence assay. We used linear regression with adjustment for age, sex, nadir CD4 count, smoking, hypertension, diabetes, and hyperlipidemia.Results:We included 231 PWH (52±9 years, 7% female). 32 (14%) had CHIP with median variant allele fraction of 3.1%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Only age was associated with CHIP (OR 2.3 per decade older, 95%CI 1.2-3.9; p=0.003). Among N=165 (CHIP=22), mean IMT was 1.0 mm with and without CHIP (p=0.63), unchanged after adjustment (Figure). CHIP was not associated with prevalent or incident plaque. Over 3.2 years, IMT progression was faster among those with CHIP (0.033 mm/year; p=0.10), attenuated after adjustment (0.022 mm/year; p=0.27). Among 80 with FDG-PET, CHIP (n=12) was associated with higher lymph node activity (SUV p=0.04) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with arterial inflammation (p=0.83), inflammatory markers, or viral persistence markers.Conclusions:Among PWH, CHIP mutations were not associated with subclinical atherosclerosis or arterial inflammation, proposed mechanisms of how CHIP could cause CVD. Clinical outcomes studies are needed to ascertain the impact of CHIP on CVD in HIV.
Abstract 15709: Antagonist of Growth Hormone-Releasing Hormone Receptor Protects Against Cardiopulmonary Injury Induced by rVSV-SARS-CoV-2-S Virus Through Rag2 Regulation
Circulation, Volume 148, Issue Suppl_1, Page A15709-A15709, November 6, 2023. Background:SARS-CoV-2 (COVID-19) transmits a multi-systemic disease that can lead to acute respiratory distress syndrome. Growth hormone-releasing hormone receptor (GHRH-R) and its splice variant are expressed in murine and human lung and heart. GHRH-R antagonist, MIA-602, has been shown to regulate inflammation in animal models and immune cell responses to bleomycin lung injury. Using a BSL2-compatible recombinant VSV-eGFP-SARS-CoV-2-S virus (rVSV-SARS-CoV-2-S) which mimics native SARS-CoV-2 infection in K18 hACE2tg mice, we tested our hypothesis that MIA-602 attenuates COVID-19-induced cardiopulmonary injury by reducing inflammation.Methods:Male and female K18-hACE2tg mice were infected with SARS-CoV-2/USA-WA1/2020, rVSV-SARS-CoV-2-S, or PBS and lung viral load, weight-loss and histopathology were compared (N=8). Mice infected with rVSV-SARS-CoV-2-S were subject to daily subcutaneous injections of 10 μg MIA-602 or vehicle (control) starting at 24h post-infection. Pulmonary function was measured via whole-body plethysmography on day 0, day 3, and day 5 (n=7). Five days after viral infection mice were sacrificed, and blood and tissues collected for histopathological analyses, H&E staining, RNA and protein work. Heart and lung tissues were used for RNASeq (n=3 per group). T-test or One-way ANOVA-test was used for statistical analysis.Results:SARS-CoV-2 and rVSV-SARS-CoV-2-S presented similar pathology for weight loss, infectivity (~60%) and histopathologic changes. Daily treatment with MIA-602 ameliorated weight loss, reduced lung inflammation, pneumonia and pulmonary dysfunction evidenced by rescued respiratory rate, expiratory parameters, and dysregulated airway parameters (p
Abstract 15132: Proteomic Signatures of Human Immunodeficiency Virus-Associated Subclinical Left Atrial Dilation
Circulation, Volume 148, Issue Suppl_1, Page A15132-A15132, November 6, 2023. Introduction:Persons living with HIV (PLWH) receiving combination antiretroviral therapy (cART) are at higher risk of heart failure (HF) and preceding cardiac abnormalities, including left atrial (LA) dilation, compared to persons without HIV (PWOH). Mechanisms of this excess risk are unclear. We assessed whether plasma proteomic signatures of immune activation are cross-sectionally associated with LA volume index (LAVi) and augmented among PLWH.Methods:We performed Olink proteomics on plasma obtained concurrently with cardiac magnetic resonance among PLWH and PWOH. Proteins were analyzed individually and as clusters agnostically defined using weighted gene co-expression network analysis. Associations with HIV serostatus and LAVi were estimated using multivariable linear regression with robust variance. We explored protein relationships using annotated enrichment analysis.Results:Among 352 participants (age 55±6 years; 25% female; 70% Black), mean LAVi was 29±9 mL/m2and 60% were PLWH (88% on cART; 73% with undetectable plasma HIV RNA). Of 2594 proteins, 104 were independently associated with LAVi (false discovery rate, FDR
Abstract 17360: Epstein Barr Virus in the Heart: A Case of Infectious Mononucleosis Causing Myopericarditis
Circulation, Volume 148, Issue Suppl_1, Page A17360-A17360, November 6, 2023. Introduction:The most common causes of myopericarditis are Coxsackie B followed by Coxsackie A, Echovirus, and Poliovirus. However, Epstein Barr Virus (EBV) may uncommonly cause myopericarditis and can mimic acute coronary syndrome (ACS).Case:A 19-year-old healthy non-smoker male presented with acute onset of central, positional chest pain preceded by a 5 day-long course of viral prodromal symptoms including sore throat. EKG showed inferolateral ST segment elevations (Figure 1). HS-Troponin T was markedly elevated (initial; 988, 1 hour; 1171). He was started on ibuprofen and colchicine for suspected myopericarditis. TTE showed LVEF 50% with borderline mild posterior and lateral wall hypokinesis with no pericardial effusion (Figure 1). Although, the presentation and PR depression were consistent with pericarditis, focal wall motion abnormality led to consideration of right or circumflex CAD such as coronary dissection. This was ruled out by coronary angiogram (Figure 2). Cardiac MRI demonstrated the epicardial pattern of gadolinium enhancement consistent with myopericarditis (Figure 2). Subsequently, patient tested positive for IgG (6.4) and IgM (3.2) [normal range 0.8 to 1.1] against EBV Capsid Antigens with unremarkable remaining viral panel results. His symptoms improved significantly with ibuprofen and colchicine. He was also treated with metoprolol succinate and lisinopril due to reduced ejection fraction.Conclusions:Cardiac complications from EBV infection are uncommon. Sometimes, the EKG with pericarditis can mimic ACS warranting an invasive test. Therefore, clinicians must maintain a high level of suspicion for myopericarditis resulting from EBV.
Abstract 11882: Acute Cardiac Events Among Older Adults Hospitalized With Laboratory-Confirmed Respiratory Syncytial Virus
Circulation, Volume 148, Issue Suppl_1, Page A11882-A11882, November 6, 2023. Introduction:Respiratory syncytial virus (RSV) can cause severe illness among older adults, but potential cardiac complications have not been comprehensively described. We evaluated the frequency and severity of acute cardiac events among older adults hospitalized with laboratory-confirmed RSV to inform recommendations for RSV vaccine candidates in development.Methods:The RSV-Associated Hospitalization Surveillance Network (RSV-NET) abstracted medical record data among all hospitalized patients identified with laboratory-confirmed RSV infection (clinician-ordered testing) in a population-based catchment area of 38 counties in 9 states. Among adults aged ≥50 years hospitalized with RSV during the 2015-16 to 2017-18 RSV seasons, we estimated the period prevalence and 95% confidence interval (CI) of acute cardiac events, identified from the patient’s discharge diagnoses and ICD-10 codes. Multivariable generalized estimating equation models estimated the adjusted risk ratio (aRR) of intensive care unit (ICU) admission and in-hospital death by acute cardiac event status.Results:Among 3959 adults aged ≥50 years hospitalized with RSV (mean age 73 years), 20.8% (CI, 19.5-22.1) experienced an acute cardiac event during hospitalization, most frequently acute heart failure (14.3%; CI, 13.2-15.4; Table). Acute cardiac events were common among adults aged ≥75 years (25.0%; CI, 23.1-27.0) and among those with underlying cardiac disease (30.4%; CI: 28.5-32.3). Compared to patients without an acute cardiac event, those with an acute cardiac event were more likely to experience ICU admission (16.8% vs 27.0%; aRR: 1.7, CI: 1.5-1.9) and in-hospital death (4.1% vs 8.8%; aRR: 2.0, CI: 1.6-2.5).Conclusions:One in 5 older adults hospitalized with RSV experienced an acute cardiac event, which was associated with approximately double the risk of severe outcomes. Adults at greater risk of cardiac complications from RSV may benefit from vaccines when available.
Abstract 14877: Spike Protein of SARS-CoV-2 Virus Induces Mitochondrial Dysfunction in Swine Heart via Redox Impairment of Heme Proteins and Increasing Superoxide Generation
Circulation, Volume 148, Issue Suppl_1, Page A14877-A14877, November 6, 2023. The cellular entry of the SARS-CoV-2 virus depends on the binding of spike (S) protein to its biological ligand, ACE2. Although the virus commonly causes respiratory distress, cardiac injury can occur in COVID-19 patients, which is consistent with the expression of ACE2 in myocytes. Previous reports indicate SARS-CoV-2 proteins can target cardiac mitochondria and suppress mitochondrial function via enhancing MPTP pore opening and perturbing cardiac bioenergetics. To explore the underlying mechanism of the effect of SARS-CoV-2 on cardiac mitochondria, we measured the interactions of SARS-CoV-2 proteins with swine heart mitochondria in vitro. Incubation of recombinant S protein with isolated mitochondria significantly decreased state-3 oxygen consumption rate (OCR, 95.10 vs 65.68 nmol/min/mg) and FCCP uncoupling OCR (82.94 vs 66.95 nmol/min/mg). We further detected that S protein impaired the enzymatic activities of electron transport chain (ETC) (by 15.62% to 34.44%). However, S protein had no effect on TCA cycle enzymes, indicating the involvement of mitochondrial membrane components in decreased OCR by S proteins. Recombinant nucleocapsid (N) protein of SAR-CoV-2 had no effect on the OCR and ETC activities of swine mitochondria. S proteins decreased the intensity of mitochondrial heme spectrum determined by dithionite reduction with UV/VIS spectroscopy (by 17.52% hemea, 15.82% hemec1). The results were further assessed using isolated complex III (Cx3) and complex IV (Cx4). Treatment of isolated Cx3 and Cx4 with S protein decreased the spectral intensities of hemeaand hemec1. The spectra of both Cx3 and Cx4 were not affected by N protein. The results suggested S protein downregulates redox potentials of ETC in swine mitochondria. Treatment of swine mitochondria with S proteins enhanced superoxide (.O2–) generation by Cx1 (by 43.7%) and by Cx3 (by 10.9-fold) assessed by EPR and cytochromecreduction assays. However, we detected S proteins modestly decreased.O2–generation by swine mitochondria under state-2 condition (by 9.52%), indicating impairing pH gradient by S protein. In conclusion, the spike protein of SARS-CoV-2 virus mediates mitochondrial dysfunction of swine heart via impairing the redox function and increasing.O2–generation.
Il vaccino contro il virus sinciziale protegge per due anni
Efficacia del 67% nell’anno successivo a quello di vaccinazione
Hepatitis D Virus Infection
New England Journal of Medicine, Volume 389, Issue 15, Page 1444-1444, October 2023.
Hepatitis D Virus Infection
New England Journal of Medicine, Volume 389, Issue 15, Page 1441-1442, October 2023.
The Latest on West Nile Virus in the US
This Medical News article discusses recent US data on West Nile virus disease.
India, focolaio del virus Nipah: rischio di una nuova pandemia?
L’India sta adottando misure urgenti per fermare la trasmissione di un virus raro ma mortale che si diffonde dai pipistrelli agli esseri umani
Attesi 5 milioni di casi per l'influenza e 10 milioni per virus simili
Pregliasco: “Avrà media intensità, vaccinare anziani e fragili”
Influenza,attesi 5 milioni di casi e 10 milioni per virus simili
Pregliasco: “avrà media intensità, vaccinare anziani e fragili”
Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study
Introduction
Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.
This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the ‘net state of immunosuppression’ as well as other clinical outcomes.
Methods and analysis
This is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores.
Ethics and dissemination
The study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals.
Trial registration number
NCT05836636.
Ricoverato al S. Martino Genova paziente con 'Toscana virus'
E’ un giovane di 25 anni. Condizioni cliniche in miglioramento