Search Results for: Scoperti anticorpi che bloccano l’infezione da SARS-CoV-2 nelle cellule

Circulation, Volume 148, Issue Suppl_1, Page A13839-A13839, November 6, 2023. Introduction:Cardiovascular (CV) involvement in multisystem inflammatory syndrome in children (MISC) is frequent (80-85%). Data on 2D speckle tracking echocardiography and its value in predicting CV outcomes are limited.Hypothesis:We hypothesized that an association exists between 2D speckle tracking strain/strain rate parameters at admission and adverse CV outcomes during hospitalization (inotropic support, major arrhythmias, cardiac arrest, ECMO, death, or transplant).Methods:We performed a multicenter (33 centers) cohort study on MISC patients hospitalized from 03/2020 to 11/2021 with at least one echocardiogram read by the Core Lab. The association between each 2D speckle tracking strain parameter and adverse CV outcomes was assessed by logistic regression.Results:Of 349 patients (median age 8.7 years [IQR 5.3,12.9]), 122 (35%) had decreased left ventricle (LV) ejection fraction (EF) and 156 (45%) had depressed LV 4-chamber longitudinal strain (LS) or basal circumferential strain (CS) during hospitalization. Worst EF and strain occurred around 5 days of illness. Of those with abnormal LS or CS strain, 50% normalized in ≤1 week, 95% within 50 days. Adverse CV outcomes occurred in 121 (35%) patients. Patients with adverse outcomes were older (p=0.003), more likely to have an underlying metabolic/genetic disorder (p=0.015), abnormal troponin (p

Circulation, Volume 148, Issue Suppl_1, Page A13849-A13849, November 6, 2023. Introduction:Patients with left ventricular assist devices (LVAD) are at increased risk for SARS-CoV-2 (COVID-19) complications. There is paucity of literature on factors influencing outcomes of LVAD patients with COVID-19 infection.Methods:A single center retrospective chart review of LVAD patients diagnosed with COVID-19 between March 2020 and March 2023, was performed to define the clinical characteristics and outcomes in this cohort. Demographics, clinical, laboratory, and imaging variables were analyzed.Results:Of 130 LVAD patients, 34 (26.2%) developed COVID-19. The cohort comprised of 27 males (79.4%) with a median age of 63.5 years and BMI of 27.6 (Table 1). Twenty-one had non-ischemic cardiomyopathy (61.8%) with either Heartmate 2 or Heartmate 3 LVADs (38.2% each). Most patients reported NYHA class III (44.1%). The common comorbidities included hypertension (94.1%), hyperlipidemia (79.4%), atrial fibrillation (67.4%), and chronic kidney disease (61.8%). Twenty-eight (82.4%) patients were hospitalized and 2 (7.1%) required mechanical ventilation (Table 2). The average initial and peak INR were 2.39 and 3.26, respectively. No complications of pump hemolysis or thrombosis, or systemic embolisms were noted. Two deaths were reported: one passed away while in the hospital from COVID-19, and another 16 months later due to sequelae of post-COVID pulmonary fibrosis.Conclusions:This is the largest single center study analyzing outcomes of COVID-19 in LVAD patients to date. Our cohort experienced a lower mortality rate from COVID-19 infection compared to prior studies. Larger studies are needed to guide management strategies and analyze long-term outcomes.

Circulation, Volume 148, Issue Suppl_1, Page A18758-A18758, November 6, 2023. Background:Over 80% of people with advanced heart failure (HF) experience pain; however, little is known about the relationship between pain and quality of life (QoL).Research Objectives:Examine the relationships between: 1) Total Pain Theory constructs and 2) pain and QoL across time.Methods:A secondary analysis of usual care participants in the ENABLE CHF-PC, a palliative care RCT (ClinicalTrials.gov: NCT02505425). Primary outcome was pain (PROMIS Pain Intensity & Interference). Total Pain constructs include physical and mental health (PROMIS Global Health 10), social support (Multidimensional Scale of Perceived Social Support), and spirituality (Negative Religious Coping). Mixed models assessed the relationships between pain and Total Pain constructs. Cross-lagged path analysis examined the temporal relationship between pain and QoL (baseline, 24-weeks, 48-weeks).Results:Of 205 usual care participants, mean age was 64.15 (SD 9.14), 108 (52.7%) men, and 111 (54.1%) African American. At baseline, participants’ QoL was poor (35.98, SD 10.7) with greater pain interference (54.5, SD 10.70) but not pain intensity (45.09, SD 10.47) compared to the general population. Among Total Pain constructs, only physical health was significant. As physical health decreased, pain intensity (b = -0.80, SE = 0.09, CI = -0.99, -0.62, p < .001) and pain interference (b = -0.69, SE = 0.10, CI = -0.89, -0.49, p < .001) increased. An unadjusted path analysis suggested variable magnitude temporal relations: a significant, large relationship between pain intensity and QoL at baseline (standardized cov. = 0.53), but medium-sized across baseline to 24-weeks (B = 0.28), and across 24- to 48-weeks (B = 0.32). Relationship between pain interference and QoL was also significant at baseline (standardized cov. = 0.54) and across baseline to 24-weeks (B = 0.41).Conclusions:Variability in magnitude of relationships between pain intensity and interference and QoL demonstrates the complex nature of pain in advanced HF.

Circulation, Volume 148, Issue Suppl_1, Page A15792-A15792, November 6, 2023. Introduction:Pericoronary fat attenuation index (pFAI) is a marker of coronary inflammation, a key step in atherosclerotic plaque formation. COVID-19 infection has also been shown to be associated with significant systemic inflammation. The aim of this study is to assess the impact of active COVID-19 infection on pFAI.Methods:Cases consisted of patients with acute or subacute COVID-19 infection who underwent clinically indicated coronary computed tomography angiography (CCTA) and were matched 1:3 on clinical and cardiovascular risk factors to controls having no prior or active COVID-19 infection. pFAI was measured for all 3 major epicardial coronary vessels (LAD, LCx and RCA). Per-vessel and per-patient analysis were done. SARS-COV-2 variant was determined as the predominant variant at the time of diagnosis.Results:We included 102 cases matched to 386 controls (64 ± 12 years, 42% men). Mean pFAI in overall cohort was higher in COVID-19 cases vs controls on both per patient (mean: -75.16 vs -77.15, p=0.024; LAD: -75.98 vs -78.65, p=0.004, LCx: -72.56 vs -74.38, p=0.047)(Figure 1a)and per-vessel (-75.17 vs -77.13, p=0.0001) analyses. Results of subgroup analysis of patients with no CAD and patients with CAD-RADS 0 showed a similar trend(Figure 1b-1c). In univariable linear regression, there was a positive association between COVID-19 and pFAI for mean per patient (beta coefficient=1.90, 95% CI: 0.26 – 3.53, p=0.02) and per-vessel (beta coefficient=1.96, 95% CI: 0.85 – 3.07, p=0.00) analyses. The association remained significant after adjusting for age, sex, and cardiovascular risk factors.Conclusions:There is a weak but statistically significant association between COVID-19 infection and elevated pFAI.

Circulation, Volume 148, Issue Suppl_1, Page A18084-A18084, November 6, 2023. Introduction:SARS-CoV-2 infection has been linked to thrombosis and bleeding. In this study we aim to investigate coagulopathy rates, predictors and in-hospital outcomes in a nationally representative sample of COVID-19 patients.Methods:Using the 2020 National Inpatient Sample. We identified adult patients who were admitted with a principal diagnosis of COVID-19. Mortality difference, LOS, and COC were evaluated as indicators of healthcare resource usage. Regression analysis adjusted for baseline variables and comorbidities compared individuals who developed coagulopathy to those who did not. Logistic regression analysis was used to identify COVID-19 coagulopathy facrtors. p-value

Circulation, Volume 148, Issue Suppl_1, Page A12680-A12680, November 6, 2023. Introduction:Cardiovascular disease (CVD) is a leading cause of mortality worldwide. The early post-hospitalization period following COVID-19 infection is critical due to high incidences of rehospitalization and deaths.Aim:To study the impact of CVD on the first 3 months after hospitalization for COVID-19.Methods:An international registry “ACTIV SARS-CoV-2” (NCT04492384) was established to characterize the course of COVID-19 in the Eurasian region and included 7 countries. The presented subanalysis used data of patients hospitalized during the acute phase of COVID-19. The post-COVID period was assessed based on telephone surveys of the patients 3 months (n=3099) after recovery.Results:79.8% of patients required unscheduled medical care in the first three months post-recovery from SARS-CoV-2 infection, with 11.8% necessitating rehospitalization. Decompensation of various CVDs was the most common reason for unscheduled medical care (Table 1).The presence of CVD in people who had COVID-19, significantly increased the likelihood of death in the first 3 months after discharge from the infectious diseases hospital (OR 4.93; 95% CI 2.53-10.8; p

Circulation, Volume 148, Issue Suppl_1, Page A14677-A14677, November 6, 2023. Introduction:SARS-CoV-2 has been linked to development of autoimmune diseases. We describe a case of a patient with untreated thymoma who developed 2 cross-reactive autoantibodies between thymus and brain: collapsing response mediator protein-5 (CRMP-5) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid receptor (AMPAR), triggered by SARS-CoV-2, inducing encephalitis and coma. Emergency thymectomy reduced anti-CRMP-5 and anti-AMPAR antibodies and restored patient neurologic function within 3 months.Description of Case:A 31-year-old male with a known history of thymoma with myasthenia gravis presented with a 1-day history of memory loss, hallucinations, ataxia, involuntary movements, and tachypnea. Rapid nasal swab COVID-19 test was positive. Over several hours, the patient became unresponsive, requiring urgent intubation for airway protection. Brain computed tomography and magnetic resonance imaging with gadolinium showed no abnormalities. Cerebrospinal fluid (CSF) analysis revealed leukocytosis with lymphocytic predominance. Four days later, CSF and serum were tested for and demonstrated high levels of CRMP-5 and AMPAR antibodies, consistent with autoimmune encephalitis. Complete robotic thymectomy was performed. Pathologic analysis revealed type B2 thymoma with negative resection margins. Three months after surgical intervention, antibody titers normalized, the patient regained consciousness, and had no neurologic deficits.Discussion:Surgical thymectomy effectively treats autoimmune encephalitis in patients with thymoma and positive CRMP-5 and AMPAR antibodies in the setting of SARS-CoV-2 infection. This rare condition is typically seen in patients with thymoma or small cell lung cancer who experience acute viral infection. Although autoantibodies to CRMP-5 and AMPAR are known to be induced by viral infection, this is the first time it has been reported for SARS-CoV-2. Timely surgical intervention is necessary to reverse obtundation and acute encephalitis by removing the cross reactive epitopes in the thymus gland. Future studies are needed to explore the molecular mechanism of SARS-CoV-2 induced immune dysfunction and autoimmunity involving cross-reactive epitopes in this deadly syndrome.

Circulation, Volume 148, Issue Suppl_1, Page A13200-A13200, November 6, 2023. Background:SARS-CoV-2 infection potentiates thromboinflammation contributing to poor outcomes in COVID-19. In non-critically ill patients hospitalized for COVID-19, therapeutic-dose heparin improves clinical outcomes. We hypothesized therapeutic-dose heparin impacts thromboinflammatory biomarkers in patients hospitalized for COVID-19 infection.Methods:We conducted a pre-specified secondary analysis of a multi-platform open-label, randomized trial comparing therapeutic-dose versus usual-care thromboprophylaxis-dose heparin in non-critically ill patients hospitalized for COVID-19. Inflammatory markers were analyzed using Wilcoxon rank-sum test and compared based on treatment. Ordinal logistic regression models evaluated for relative D-Dimer change (measured at baseline, day 1, day 3). Odds ratio of a 3-level ordinal outcome (death, survival with organ support, or survival without organ support through 21 days) was determined for relative change.Results:Of 1510 patients, 528 had a D-Dimer on baseline and day 1, and 432 on baseline and day 3. Median age was 60 years (IQR: 50-69) with 41% female and 66% under-represented minorities. Compared to usual-care, therapeutic-dose heparin was associated with a greater drop in D-Dimer at days 1 and 3; other biomarkers were unaffected by treatment (Table 1). D-Dimer at baseline and day 1 had an OR 0.93 (95% CI: 0.88, 0.98) whereas baseline and day 3 had an OR 0.86 (95% CI: 0.78, 0.94) of the ordinal outcome translating in a higher odds of surviving without the need for organ support (adjusted for treatment, gender, and age).Conclusion:In this randomized controlled trial therapeutic-dose heparin was associated with an early reduction in D-Dimer and clinical improvement, suggesting thromboinflammatory mechanisms whereby treatment conferred a clinical benefit. Temporal changes in D-dimer could predict treatment response or may signal need for alternative therapies.

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

Circulation, Volume 148, Issue Suppl_1, Page A17669-A17669, November 6, 2023. Introduction:Racial, regional, and income disparities have been shown to impact cardiovascular outcomes in postmenopausal women with SARS-CoV-2. Addressing these disparities can improve healthcare equity and outcomes for this vulnerable population.Methods:A retrospective cohort study utilized data from the National Inpatient Sample (NIS)-2020 to examine female patients aged over 55 years who were admitted to hospitals in 2020. The study focused on primary endpoints, specifically major cardiac and cerebrovascular events (MACCE) including all-cause mortality, AMI, cardiac arrest, and stroke. Multivariable logistic regression was used to evaluate the association between demographic factors and cardiovascular outcomes, after controlling for confounding variables.Results:Of the total 547,225 postmenopausal women hospitalized with SARS-CoV-2, 19.8% had MACCE. Racial disparities were significant, as Native American, Hispanic, Asian and African American women exhibited higher rates of MACCE compared to Caucasian women, with odds ratios (OR) of 1.63 (95% CI: 1.33-1.98, p

Circulation, Volume 148, Issue Suppl_1, Page A18072-A18072, November 6, 2023. Introduction:Myocarditis (MC) and multiple sclerosis (MS) are inflammatory affectations of the myocardium and the central nervous system, respectively. It has been suggested that MS and MC share similar immunological dysfunctions. MS and MC also have associations with viral infection, and SARS-CoV-2 specifically has been associated with MC, indicating that a viral infection may induce or enhance a dysfunctional immune response favored by individuals’ genetic susceptibility.Hypothesis:We hypothesized that patients with preexisting MS may be more susceptible to COVID-19-related MC.Methods:A retrospective study was conducted using the PearlDiver database (PearlDiver Technologies, Fort Wayne, IN). Using ICD codes, a cohort of patients admitted for COVID-19 as the primary diagnosis (index event) was identified. The cohort then was divided into two groups based on the presence of MS upon admission. The records of both groups were compared by demographics and a panel of 16 comorbidities. Pearson’s chi-square and t-test were used to compare the group’s characteristics when appropriate. A Kaplan-Meier analysis was then used to compare the probability of the outcome (MC) 90 days following the index event. A p-value of

Circulation, Volume 148, Issue Suppl_1, Page A12600-A12600, November 6, 2023. Introduction:Among individuals with active SARS-CoV-2 (COVID-19) infection, emerging evidence suggests that pulmonary hypertension (pHTN) of any etiology may be associated with poor outcomes. We studied the in-hospital population with pHTN and COVID-19 infection.Hypothesis:Studying the impact of COVID-19 on pHTN patients is essential and may inform optimizing patient management and improving outcomes.Methods:We derived our sample using the 2020 National Inpatient Sample Database (NIS) discharge data. Our population was patients with a primary admission diagnosis of COVID-19 identified using the ICD 10 code U071. We divided this sample into two groups based on a secondary diagnosis of pHTN or no pHTN. We used multivariate logistic regression analysis to account for confounders and estimate the probability of our outcomes.Results:There were 1,058,815 primary hospitalizations for COVID-19, and 2.37% (25,070) had pHTN, with a female predominance of 56.8% and a mean age of 71.3 years ±14.7. By ethnicity, 58.7% were Caucasians, 22.1% were Blacks, and 12.9% were Hispanics. Following multivariate analysis, we found that pHTN was associated with significantly higher odds of pulmonary embolism (PE), adjusted odds ratio (aOR) 2.2 (1.9-2.5, p

Circulation, Volume 148, Issue Suppl_1, Page A12759-A12759, November 6, 2023. Introduction:Scattered studies suggest that SARS-CoV-2 spike protein (SP) promotes platelet activation, though the exact mechanism is unknown. Thymidine phosphorylase (TYMP), which facilitates platelet activation and thrombosis, is significantly increased in the plasma and lungs of COVID-19 patients, suggesting that TYMP may play a role in the COVID-19 milieu.Hypothesis:We hypothesize that TYMP enhances SP/platelet factor 4 (PF4) complex formation and inhibition of TYMP attenuates SP-induced thrombosis and/or inflammation.Methods:BEAS-2B cells were treated with SP- or its receptor binding domain (RBD)-containing COS-7 cell lysate, or control cell lysate (p3.1) and TYMP and STAT3 expression were determined by western blot. The effect of SP on thrombosis was examined in K18-hACE2 and K18-hACE2/Tymp-/-mice using the ferric chloride-induced carotid artery injury thrombosis model. SP-, TYMP-, or PF4-encoding plasmids were co-transfected into COS-7 and their protein interactions were assessed using co-IP, Blue Native-PAGE, and immunocytochemistry.Results:SP increased expression of TYMP and pY705-STAT3 in BEAS-2B. siRNA-mediated knockdown of TYMP reduced STAT3 activation. SP significantly enhanced thrombosis in the K18-hACE2 mice, which was inhibited by simultaneously treating mice with tipiracil, a selective TYMP inhibitor (Figure). K18-hACE2/Tymp-/-mice were resistant to SP-enhanced thrombosis. For the first time, we found that SP, PF4, and TYMP form a complex whose formation is dose-dependently enhanced by TYMP.Conclusions:Our studies suggest that SARS-CoV-2 SP enhances TYMP expression and is prothrombotic and proinflammatory. TYMP inhibition, either via genetic knockout or by its chemical inhibitor, attenuates SP-enhanced thrombosis. TYMP promotes the formation of a PF4/SP complex, which provides a novel insight into COVID-19-associated thrombosis. TYMP could be a novel therapeutic target for COVID-19-associated sequelae.

Circulation, Volume 148, Issue Suppl_1, Page A19206-A19206, November 6, 2023. Introduction:Early evidence showed SARS-CoV-2 infection was associated with increased risk of acute cardiovascular complications. COVID-19 has since been implicated in intermediate and long-term cardiovascular disease. However, the impact of COVID-19 on heart disease mortality for specific demographic groups has not been investigated. Goals: This study aimed to determine whether excess heart disease mortality was COVID-19 related and whether differences existed by race/ethnicity, gender, and age.Research Question: What was the excess heart disease mortality associated with COVID-19 in 2020 and 2021?Methods:Death certificate and population data (2010-2021) for Black, White, and Hispanic adults were analyzed. Deaths with diseases of the heart (DOH) as either underlying or contributing cause were included (ICD-10 I00-I09, I11, I13, I20-I51). We fit a log-linear regression model to annual death rates for 2010-2019. Model coefficients were used to estimate expected DOH death rates for 2020-2021. We then compared observed to expected DOH mortality rate ratios and rate differences by age, sex, and gender for those pandemic years. The proportion of excess DOH deaths which had COVID-19 reported on the death certificate was calculated.Results:From 2010-2019, mortality from DOH was highest among Black men. Ratios of observed to expected DOH mortality rates for 2020-2021 were highest among younger ages (25-44 years), men, and Hispanics and Blacks compared to Whites. The proportion of excess DOH deaths with reported COVID-19 was highest among Hispanics compared to other demographic groups across all ages except those 85+. Seventy-five and 78 percent of excess deaths among Hispanic adults 55-64 years were COVID-19 related.Conclusion:Excess deaths during the COVID-19 pandemic were highest among young Black men and COVID-19 was more often reported with excess DOH deaths among Hispanic adults. Findings are consistent with other evidence of disproportionate negative social and structural impacts of COVID-19 among Black and Hispanic communities.

Circulation, Volume 148, Issue Suppl_1, Page A13173-A13173, November 6, 2023. Introduction:COVID-19 disproportionately affects older, male obese patients leading to a high prevalence of adverse outcomes. SARS-CoV-2 mediated ACE2 loss may further increase the susceptibility of these patients to adverse outcomes. Loss of ACE2 may be a causative factor in cardiovascular (CV) injury independent of primary viral-mediated injury.Methods:Male, 6-month-old, diabetic, obesedb/db Ace2-/y(double mutant, DM) mice and respective WT,Ace2-/y, anddb/dbcontrols (n=12) were assessed for injury across the gut-heart axis. Cardiovascular parameters were evaluated by echocardiography, pressure-volume loops, and histology. Alterations in gut permeability were determined by measuring plasma peptidoglycan (PGN) levels and immunological staining of microvilli structure. Metagenomics and metatranscriptomics determined the functional and phyla alterations of the gut microbiota.Results:Loss of ACE2 in diabetic obese mice led to increased left atrium diameter (P

Circulation, Volume 148, Issue Suppl_1, Page A16437-A16437, November 6, 2023. IntroThere are many complications because of COVID-19 infections. These have ranged from organ dysfunctions to severe disease states. The global nature of SARS-CoV-2 pandemic has allowed clinicians to discover new pathophysiology associated with infections. We present a case of a patient with severe hypertriglyceridemia (HTG) after a SARS COVID-19 infection and propose a correlation between his infection and elevated triglyceride (TG) levels.CaseA 64 y/o man living with a history of HFpEF, COPD, and HLD presented to our clinic after being diagnosed with SARS-CoV-2 infection two days prior. He had upper respiratory symptoms of a productive cough, fevers, decreased appetite, and mild dyspnea with exertion not requiring supplemental oxygen. He was prescribed paxlovid and discharged home. On follow up his symptoms had improved. He was due for a repeat lipid level and this was drawn during his visit. His last lipid panel results were normal. His repeat TG was 2,186 mg/dL. It was thought his levels were elevated because of his SARS-CoV-2 infection. His fasting TG levels were repeated and found to have normalized with a low-fat diet alone and had no further interventions.DiscussionThere have been few reports demonstrating a rise in TG levels after SARS-CoV-2 infections. Hepatic injury secondary to the infection or medications prescribed for treatment may lead to elevated TGs levels. When these are excluded, it is unknown what leads to HTG. Studies have evaluated lipoprotein lipase (LPL) activity levels and how they were decreased after SARS-CoV-2 infections. LPL assists in the metabolism of TG’s and activity is decreased in many disease states. It is thought that the COVID-19 infection causes HTG secondary to acquired LPL deficiency. These patients require close monitoring to decrease complications.ConclusionHTG is known to cause increased incidence of pancreatitis and ASCVD events. While treating these, one must assess the underlying etiology that led to the disease state. In patients found to have elevated TG levels it is important to include questions pertaining to recent infectious processes. Further research is needed to deduce how infectious processes can lead to elevated TG levels. Treatment consists of initiating a low-fat diet and may include fibrates.