Search Results for: Trattamento domiciliare di un paziente positivo al virus SARS-Cov-2

Luxenburger H, Thimme R. SARS-CoV-2 and the liver: clinical and immunological features in chronic liver disease. Gut 2023;72:1783-94
The correct legend for figure 4 should be:
Effect of booster vaccination on the adaptive immune response in LTR and AIH patients (A) Booster vaccination significantly improves the SARS-CoV- 2-specific antibody response in AIH, while the frequency of T cells remains stable. (B) Booster vaccination significantly improves the SARS-CoV-2- specific antibody response in LTR, while the frequency of T cells remains stable. (C) After two RNA vaccine doses, the CD4+T cell subset distribution is altered in LTR with lower frequencies of TFH cells, however, the frequencies increase after booster infection. AIH, autoimmune hepatitis; LTR, liver transplant recipients; TFH cells: T follicular helper cells.

We read Kennedy et al1’s findings with interest, and report in-depth analyses of antibody and T cell responses in patients with inflammatory bowel disease (IBD) to COVID-19 vaccination. We prospectively recruited 100 SARS-CoV-2-uninfected patients with IBD on varying treatments at the Royal Melbourne Hospital (HREC/74403/MH-2021). Healthcare workers who did not have IBD and were not on immunosuppressive medication were enrolled as controls with approvals from Melbourne Health (HREC/68355/MH-2020) and University of Melbourne (HREC 22268, 21626). Participant characteristics are outlined in table 1. IBD medication regimens needed to be stable for at least 8 weeks prior to enrolment. Only one participant was on concomitant low-dose systemic corticosteroids with anti-TNF combination therapy. Eighty-nine patients received BNT162b2 (Pfizer–BioNTech), and 11 received ChAdOx1 nCoV-19 (Oxford–AstraZeneca). No participants had a clinical history of SARS-CoV-2 infection at enrolment. Anti-S1/2 and anti-RBD SARS-CoV-2-specific antibodies were measured at baseline and at five time…

Objectives
Chronic hepatitis B (CHB) caused by HBV infection greatly increases the risk of liver cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) plays critical roles in the pathogenesis of CHB. HBsAg loss is the key indicator for cure of CHB, but is rarely achieved by current approved anti-HBV drugs. Therefore, novel anti-HBV strategies are urgently needed to achieve sustained HBsAg loss.

Design
We developed multiple chimeric antigen receptors (CARs) based on single-chain variable fragments (scFvs, namely MA18/7-scFv and G12-scFv), respectively, targeting HBV large and small envelope proteins. Their impacts on HBsAg secretion and HBV infection, and the underlying mechanisms, were extensively investigated using various cell culture models and HBV mouse models.

Results
After secretory signal peptide mediated translocation into endoplasmic reticulum (ER) and secretory pathway, MA18/7-scFv and CARs blocked HBV infection and virion secretion. G12-scFv preferentially inhibited virion secretion, while both its CAR formats and crystallisable fragment (Fc)-attached versions blocked HBsAg secretion. G12-scFv and G12-CAR arrested HBV envelope proteins mainly in ER and potently inhibited HBV budding. Furthermore, G12-scFv-Fc and G12-CAR-Fc strongly suppressed serum HBsAg up to 130-fold in HBV mouse models. The inhibitory effect lasted for at least 8 weeks when delivered by an adeno-associated virus vector.

Conclusion
CARs possess direct antiviral activity, besides the well-known application in T-cell therapy. Fc attached G12-scFv and G12-CARs could provide a novel approach for reducing circulating HBsAg.

Basic scienceComplement dysregulation in long COVID Cervia-Hasler C, Bruningk S, Hoch T, et al. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Science 2024; doi: 10.1126/science.adg7942. There is currently a lack of diagnostic and therapeutic tests for patients affected by long COVID (coronavirus disease). In this multicentre, longitudinal study, a total of 113 SARS-CoV-2-infected patients and 39 healthy controls were prospectively followed up for 1 year with serial serum collected for analysis. A total of >6500 proteins in the serum were measured using the SomaScan (Slow Off-rate Modified Aptamer Scan) platform with top candidate biomarkers being identified using computational tools. Cervia-Hasler et al showed that terminal complement complexes (TCCs) were most differentially expressed in 6-month long COVID patients, compared with healthy controls, patients without long COVID and patients hospitalised for other reasons, confirming the presence of dysregulated complement system. At 6-month follow-up, those with…

Objective
A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg).

Design
Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients. We measured cirB-RNA, HBV DNA, hepatitis B surface antigen (HBsAg), HBcrAg and alanine aminotransferase levels. cirB-RNA was quantified using an investigational HBV RNA assay for use on the cobas 6800 system. The test detects a region spanning the HBV canonical polyadenylation site. cccDNA and 3.5 kb RNA in liver tissue were assessed by quantitative PCR and droplet digital PCR.

Results
cirB-RNA was detectable in 100% of HBeAg(+) chronic hepatitis (CH), 57% and 14% of HBeAg(–) CH and chronic infection untreated patients and 47% of NUC-treated patients. cirB-RNA undetectability was associated with lower intrahepatic cccDNA transcriptional activity, as well as serum HBcrAg, but no significant differences in HBsAg, in both untreated and treated patients. In untreated HBeAg(–) patients, cirB-RNA correlated with intrahepatic 3.5 kb RNA and cccDNA transcriptional activity, serum HBV DNA and HBcrAg, but not with HBsAg or total cccDNA levels. Combined undetectability of both cirB-RNA and HBcrAg detection in untreated HBeAg(–) patients identified a subgroup with the lowest levels of intrahepatic transcriptionally active cccDNA.

Conclusion
Our results support the usefulness of quantification of circulating HBV RNA expressed from cccDNA as an indicator of intrahepatic active viral reservoir in both untreated and NUC-treated CHB patients.

Trial registration number
NCT02602847.

Although safe and effective vaccines against HBV (hepatitis B virus) are available, there are worldwide more than 2 billion people who had an HBV infection and about 250 million people suffering from chronic HBV infection. Chronic HBV infection is a major cause for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It is estimated that about 800 000–1 000 000 people die each year due to the consequences of chronic HBV infection.1 Moreover, in almost all HBV-associated HCCs integrated HBV-DNA is found. Therapy options at present are limited and based on nucleoside/nucleotide analogues and interferon alpha. Since persistence of HBV infection frequently can be attributed to an insufficient cellular immune response approaches to rescue host immune response may help to eliminate infected cells and to suppress virus replication. A recent development are HBV-specific CARs (chimeric antigen receptors) human T-cells that are intended to recognise and eliminate HBV positive…

Stroke, Ahead of Print. BACKGROUND:Ischemic stroke is often accompanied by oxidative stress and inflammatory response, both of which work synergistically to exacerbate the disruption of the blood-brain barrier and ischemic brain injury. ALK (anaplastic lymphoma kinase), a cancer-associated receptor tyrosine kinase, was found to play a role in oxidative stress and inflammation. In this study, we investigated the role of ALK inhibition in a murine model of ischemic stroke.METHODS:Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery in mice with a filament. The ALK inhibitor alectinib was administered following the stroke. ALOX15 (arachidonic acid 15-lipoxygenase) was overexpressed by adenovirus injection. The immunohistochemistry, Western blot, oxidative stress, inflammation, blood-brain barrier leakage, infarct volume, and functional outcomes were determined.RESULTS:We found that the expression of ALK was markedly increased in the neurovascular unit after cerebral ischemia. Treatment with the ALK inhibitor alectinib reduced the accumulation of reactive oxygen species, lipid peroxidation, and oxidative DNA, increased the vascular levels of antioxidant enzymes, inactivated the vascular NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome pathway, and reduced vascular inflammation (ICAM-1 [intercellular adhesion molecule-1] and MCP-1 [monocyte chemoattractant protein-1]) after ischemia. Moreover, alectinib reduced the loss of cerebrovascular integrity and blood-brain barrier damage, consequently decreasing brain infarction and neurological deficits. Furthermore, alectinib reduced stroke-evoked ALOX15 expression, whereas virus-mediated overexpression of ALOX15 abolished alectinib-dependent inhibition of oxidative stress and vascular inflammation, blood-brain barrier protection, and neuroprotection, suggesting the protective effects of alectinib for stroke may involve ALOX15.CONCLUSIONS:Our findings demonstrated that alectinib protects from stroke by regulating ischemic signaling cascades and suggest that ALK may be a novel therapeutic target for ischemic stroke.

Disponibile profilassi con anticorpi monoclonali

Il trattamento va affiancato al farmaco specifico

This Medical News story discusses a recent study that found people who are immunocompromised clear SARS-CoV-2 at varying rates.

When the COVID-19 pandemic led to lockdowns and other measures to stop the spread of the deadly virus, qualitative researchers, like others, had to adapt and learn to collect their data remotely. This workshop offers a collection of tips and tricks for collecting qualitative data remotely using video conferencing software such as Microsoft Teams or Zoom, phone, and hybrid methods to accommodate their participants. We will discuss logistics of using proxies at sites to recruit and consent participants and coordinate remote interviews and focus groups. We will provide examples from real projects and discuss the pros and cons of the newly found flexibility in remote data collection, accommodations that might be needed for specific populations, platforms security to ensure confidentiality, e-consenting models and platforms, using AI for transcribing, and evaluating data collected remotely and in-person. We will also cover methods that benefit from remote data collection modes, such as physician participants showing quality metrics they collect or interviewers showing notes (e.g. journey mapping in real time with participants’ input). The workshop will teach the following skills: 1) deciding between in-person and remote data collection modes, depending on the research question and participant characteristics; 2) platforms, logistics, and best practices of implementing remote consent; 3) using on-site proxies to conduct remote data collection; 4) flexibility in remote data collection (what are your options?); 5) hands-on training, real project examples, and exercises; 6) group discussions and implications for qualitative and mixed-methods research. We believe this is an ideal time to take stock of what we have learned from collecting qualitative data under the pandemic restrictions. Now that remote data collections methods are here to stay, we need to continue developing our best practices to accommodate not only future disasters, but also people with different abilities.

In the Research Letter titled “Mortality and Hospitalization Risks in Patients With Cancer and the SARS-CoV-2 Omicron Variant,” published online November 22, 2023, an affiliation was omitted for the fourth author, Adi Turjeman, PhD. Her name has now been added to the affiliation, “Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.” This article has been corrected online.

This cohort study compares outcomes for patients with hematologic malignant tumors who prophylactically received tixagevimab-cilgavimab against SARS-CoV-2 with those who did not.

In this issue of JAMA Dermatology, Schneeweiss et al present an article examining laboratory screening and monitoring patterns in treating patients with chronic inflammatory skin diseases (CISDs) treated with systemic immunomodulatory agents. Their analysis uses a large US database of commercial insurance claims and considers patients with psoriasis, hidradenitis suppurativa, or atopic dermatitis who initiated treatment with 1 of the following systemic medications: methotrexate (MTX), tumor necrosis factor inhibitors (TNFi), interleukin (IL)–17 inhibitors, IL-23 inhibitors, ustekinumab, dupilumab, or apremilast. Schneeweiss and collaborators report inconsistencies in the clinical use of laboratory tests compared with guidelines proposed by the US Food and Drug Administration (FDA) and professional dermatology societies (eg, Joint American Academy of Dermatology–National Psoriasis Foundation guidelines), such that less than 60% of the evaluated population received recommended pretreatment testing, including tuberculosis (TB), hepatitis B virus (HBV), hepatitis C virus (HCV), and liver function tests. These observations raise important questions as we aim to provide patients with safe, effective therapies while also keeping in mind the cost of our daily clinical choices.

Objectives
To determine the most epidemiologically effective and cost-effective school-based SARS-CoV-2 antigen-detection rapid diagnostic test (Ag-RDT) self-testing strategies among teachers and students.

Design
Mathematical modelling and economic evaluation.

Setting and participants
Simulated school and community populations were parameterised to Brazil, Georgia and Zambia, with SARS-CoV-2 self-testing strategies targeted to teachers and students in primary and secondary schools under varying epidemic conditions.

Interventions
SARS-CoV-2 Ag-RDT self-testing strategies for only teachers or teachers and students—only symptomatically or symptomatically and asymptomatically at 5%, 10%, 40% or 100% of schools at varying frequencies.

Outcome measures
Outcomes were assessed in terms of total infections and symptomatic days among teachers and students, as well as total infections and deaths within the community under the intervention compared with baseline. The incremental cost-effectiveness ratios (ICERs) were calculated for infections prevented among teachers and students.

Results
With respect to both the reduction in infections and total cost, symptomatic testing of all teachers and students appears to be the most cost-effective strategy. Symptomatic testing can prevent up to 69·3%, 64·5% and 75·5% of school infections in Brazil, Georgia and Zambia, respectively, depending on the epidemic conditions, with additional reductions in community infections. ICERs for symptomatic testing range from US$2 to US$19 per additional school infection averted as compared with symptomatic testing of teachers alone.

Conclusions
Symptomatic testing of teachers and students has the potential to cost-effectively reduce a substantial number of school and community infections.