Risultati per: Identificate le origini evolutive di SARS-CoV-2

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.

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 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 A17307-A17307, November 6, 2023. Introduction:It is well known that SARS-Co-V2 infection can induce ER stress-associated activation of unfolded protein response (UPR) in various host cells which may contribute to the pathogenesis of COVID-19. However, the interplay between SARS-Co-V2 infection and UPR signaling in pre-existing ER stress associated pathological conditions has not been well elucidated.Hypothesis:We hypothesizedthat modulation of a pre-existing ER stress in host cells could attenuate susceptibility to SARS-CoV-2 infection by activating a range of cellular defense.Methods:Increasing concentrations of Tunicamycin (Tm) and Thapsigargin (Tg) have been used to induce ER stress in Huh-7 cells. After 6h treatment, cells were infected with SARS-CoV-2 pseudotyped particles (SARS-CoV-2pp) for 48 p.i. SARS-Co-V2-2pp entry was measured using Bright GloTMluciferase assay. Cell viability was measured by cell titer Glo®luminescent cell viability assay. The mRNA and protein expression of UPR markers were evaluated using RT-qPCR and Western blot methods.Results:Tm (5 μg/ml) and Tg (1 μM) efficiently inhibited SARS-CoV-2pp entry into cells without any cytotoxic effect. Chemical ER stress-induced inhibition of SARS-CoV-2pp entry was associated with significant reduction of ACE2 expression in Tg-infected cells but not with Tm. Strikingly, Tm and Tg revealed differential effects in modulating the expression of ER stress genes in infected cells. Both Tm and Tg significantly reduced the expression of stress-inducible ER chaperone GRP78/BIP in infected cells. In contrast, the IRE1-XBP1s and PERK-eIF2α-ATF4-CHOP signaling pathways were downregulated in Tg-infected cells only. Additionally, insulin-mediated glucose uptake, phosphorylation of Ser307IRS-1 and downstream p-AKT were enhanced in Tg-infected cells without any change in ERK phosphorylation.Conclusions:These findings suggest that pre-existing ER stress could modulate a specific UPR response in infected cells capable of counteracting the stress-inducible elements signaling, thereby depriving SARS-Co-V2 of essential components for their entry and replication. Pharmacological manipulation of ER stress in host cells might provide new therapeutic strategies to alleviate SARS-CoV-2 infection.

Circulation, Volume 148, Issue Suppl_1, Page A15524-A15524, November 6, 2023. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of this virus has led to millions of deaths and the long-term cardiovascular and respiratory consequences of COVID-19 continue to pose a massive threat to public health. While recent studies have demonstrated that SARS-CoV-2 may enter kidney epithelial cells via angiotensin converting enzyme 2 (ACE2)-independent mechanisms by inducing receptor-independent macropinocytosis, it is currently unknown whether this process also occurs in cell types directly relevant to SARS-CoV-2-associated cardiovascular disease or pneumonia. Here, we investigated the ability of SARS-CoV-2 spike protein subunits to stimulate macropinocytosis in alveolar epithelial cells and macrophages. Flow cytometry analysis of fluid-phase marker internalization demonstrated that SARS-CoV-2 spike protein subunits S1, the receptor binding domain (RBD) of S1, and S2 stimulate macropinocytosis in both human and murine macrophages, but not in human lung epithelial cells. Pharmacological and genetic inhibition of macropinocytosis substantially decreased spike protein-induced macropinocytosis in macrophages bothin vitroandin vivo. High resolution scanning electron microscopy (SEM) imaging confirmed spike protein-induced plasma membrane activities characteristic of macropinocytosis. Mechanistic studies demonstrated that inhibition of protein kinase C and phosphoinositide 3-kinase in macrophages blocks SARS-CoV-2 spike protein-induced macropinocytosis. Further, pharmacological blockade of ACE2 did not inhibit macropinocytosis in SARS-CoV-2 spike protein-treated cells. To our knowledge, these results demonstrate for the first time that SARS-CoV-2 spike protein subunits stimulate macropinocytosis in macrophages. These results may contribute to a better understanding of SARS-CoV-2 infection and its cardiovascular and respiratory complications.

Circulation, Volume 148, Issue Suppl_1, Page A14911-A14911, November 6, 2023. Background:SARS-CoV-2 infection can result in cardiac complications, including myocarditis, left ventricular dysfunction, arrhythmias, and acute myocardial injury. Reports of effusive constrictive pericarditis (CP) are rare, and recommendations on management are limited.Description of Case:A 30-year-old male with recurrent episodes of effusive pericarditis after SARS-CoV-2 infection 11 months prior and anasarca presents with worsening fatigue, dyspnea, and weight gain. His echocardiogram showed pericardial thickening, annulus reversus, and interventricular septal bounce. Computed tomography showed pericardial thickening and a complex pericardial effusion. Right and left heart catheterization revealed elevated filling pressures, equalization of diastolic pressures, and ventricular discordance (Figure 1). Infection, malignancy, and autoimmune etiologies of CP were ruled out.Decision Making:The patient was initiated on anti-inflammatory therapy and aggressively diuresed with no improvement in his symptoms. Given recurrent episodes of pericarditis with constriction, the patient underwent a radical pericardiectomy with posterior pericardial release. The pericardium was 1 cm thick with severe fibrosis. Surgical pathology showed acute and chronic pericarditis with negative testing for Mycobacterium tuberculosis.Conclusion:Idiopathic, post-cardiac surgery and post-mediastinal radiation are the most common causes of CP. Acute pericarditis is a known complication of SARS-CoV-2 infection, but ongoing inflammation leading to CP is rare. CP presents with signs of heart failure and should be considered in patients with persistent symptoms of pericarditis.

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.

Circulation, Volume 148, Issue Suppl_1, Page A15405-A15405, November 6, 2023. Introduction:Post-acute sequelae of SARS-CoV-2 infection consist of pulmonary and extrapulmonary conditions, including a higher incidence of type 2 diabetes, but it remains unknown whether other cardiometabolic pathways are impacted by infection.Research Question:Does SARS-CoV-2 infection predict worsening cardiometabolic risk factors?Methods:Using data from OneFlorida+ (a PCORnet CRN), we compared changes over time in body mass index (BMI), systolic blood pressure (SBP) and low-density lipoprotein (LDL). We compared an Exposed cohort with a positive SARS-CoV-2 test or COVID-19 diagnosis code between March 2020 – January 2022 (n = 75,217; age: 48.5 y, 64% female), relative to a contemporary Unexposed cohort of adult patients with negative SARS-CoV-2 tests (n = 240,575; age: 52.7 y, 61% female), and an age/sex-matched Historical control cohort (March 2018 – January 2020; n = 75,217; age: 48.5 y, 64% female). We used multiple imputation for missingness in demographic and clinical factors and inverse probability weighting for confounding and loss to follow-up. We used doubly robust marginal structural models to estimate baseline and longitudinal differences in cardiometabolic indicators by cohort.Results:At the start of the follow-up period, adjusted for covariates and relative to the Exposed, the Unexposed (BMI: -0.5 [-0.6,-0.4] kg/m2, SBP: -0.5 [-0.8,-0.2] mmHg, LDL: -7.7 [-14.5, -1.0] mg/dL) and Historical control (BMI: -0.4 [-0.5,-0.3] kg/m2, SBP: -1.0 [-1.5,-0.6] mmHg, LDL: 12.5 [-58.3, 83.3] mg/dL) cohorts had better cardiometabolic profiles (Figure). Relative to changes in the Exposed, control cohorts displayed faster decreases in BMI (Unexposed only), slower increases in SBP, and no changes in LDL during the follow-up period.Conclusions:SARS-CoV-2 infection was associated with weight retention and a rise in blood pressure. Longer follow-up can help identify stability and impacts of these cardio-metabolic indices on events and mortality.

New England Journal of Medicine, Volume 389, Issue 18, Page 1722-1724, November 2023.

Background
Predictors of COVID-19 vaccine immunogenicity and the influence of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require elucidation.

Methods
Stop the Spread Ottawa is a prospective cohort of individuals at-risk for or who have been infected with SARS-CoV-2, initially enrolled for 10 months beginning October 2020. This cohort was enriched for public-facing workers. This analysis focuses on safety and immunogenicity of the initial two doses of COVID-19 vaccine.

Results
Post-vaccination data with blood specimens were available for 930 participants. 22.8% were SARS-CoV2 infected prior to the first vaccine dose. Cohort characteristics include: median age 44 (IQR: 22–56), 66.6% women, 89.0% white, 83.2% employed. 38.1% reported two or more comorbidities and 30.8% reported immune compromising condition(s). Over 95% had detectable IgG levels against the spike and receptor binding domain (RBD) 3 months post second vaccine dose. By multivariable analysis, increasing age and high-level immune compromise predicted diminishing IgG spike and RBD titres at month 3 post second dose. IgG spike and RBD titres were higher immediately post vaccination in those with SARS-CoV-2 infection prior to first vaccination and spike titres were higher at 6 months in those with wider time intervals between dose 1 and 2. IgG spike and RBD titres and neutralisation were generally similar by sex, weight and whether receiving homogeneous or heterogeneous combinations of vaccines. Common symptoms post dose 1 vaccine included fatigue (64.7%), injection site pain (47.5%), headache (27.2%), fever/chills (26.2%) and body aches (25.3%). These symptoms were similar with subsequent doses.

Conclusion
The initial two COVID-19 vaccine doses are safe, well-tolerated and highly immunogenic across a broad spectrum of vaccine recipients including those working in public facing environments.

The antiviral drug molnupiravir was linked with a pattern of genomic changes in SARS-CoV-2, based on an analysis in Nature of more than 15 million global sequences.

To the Editor A recent study developed a data-driven scoring framework to classify postacute sequelae of SARS-CoV-2 infection (PASC). As stated in the accompanying Editorial, prior to developing a case definition, it is important to determine whether PASC is a single entity or multiple entities. Particularly, severe COVID-19 pneumonia requiring admission to the intensive care unit may lead to specific organ dysfunction and injury, including impaired cognitive function across multiple domains. Such dysfunction, consistent with the well-described post–intensive care syndrome, should be disentangled from PASC.

In Reply We agree with Dr Batra and colleagues that different manifestations of long COVID may arise due to different underlying pathological mechanisms of disease, which may be related to whether an individual was hospitalized during the acute phase of SARS-CoV-2 infection. However, we disagree that stratification by hospitalization status was needed to ensure the validity of the approach we used in our study.

Lavinia Valbonesi, moglie di Noboa, è nutrizionista e modella

Objectives
Infections by SARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently than earlier viral lineages. We aimed to address five questions about SARS-CoV-2 VOC infections in children and adolescents: (1) symptoms and severity, (2) risk factors for severe disease, (3) the risk of infection, (4) the risk of transmission and (5) long-term consequences following a VOC infection.

Design
Systematic review.

Data sources
The COVID-19 Open Access Project database was searched up to 1 March 2022 and PubMed was searched up to 9 May 2022.

Eligibility criteria
We included observational studies about Alpha, Beta, Gamma, Delta and Omicron VOCs among ≤18-year-olds. We included studies in English, German, French, Greek, Italian, Spanish and Turkish.

Data extraction and synthesis
Two reviewers extracted and verified the data and assessed the risk of bias. We descriptively synthesised the data and assessed the risks of bias at the outcome level.

Results
We included 53 articles. Most children with any VOC infection presented with mild disease, with more severe disease being described with the Delta or the Gamma VOC. Diabetes and obesity were reported as risk factors for severe disease during the whole pandemic period. The risk of becoming infected with a SARS-CoV-2 VOC seemed to increase with age, while in daycare settings the risk of onward transmission of VOCs was higher for younger than older children or partially vaccinated adults. Long-term symptoms following an infection with a VOC were described in