Therapeutic BCG vaccine protects against long COVID: The BATTLE randomized clinical trial.

Background: Bacillus Calmette-Guérin (BCG) injected during the COVID-19 convalescence period was safe and enhanced recovery from anosmia and dysgeusia in the acute phase.

Objectives: To report the long-term results of the BATTLE trial, BCG vaccine in adults with mild COVID-19.

Methods: Design: Double-blind, placebo-controlled, randomized (1:1) clinical trial.

Diacerein reduces inflammasome activation and SARS-CoV-2 virus replication: a proof-of-concept translational study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.

Dimethyl fumarate modulates the regulatory T cell response in the mesenteric lymph nodes of mice with experimental autoimmune encephalomyelitis.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF.

Diving into the proteomic atlas of SARS-CoV-2 infected cells.

The COVID-19 pandemic was initiated by the rapid spread of a SARS-CoV-2 strain. Though mainly classified as a respiratory disease, SARS-CoV-2 infects multiple tissues throughout the human body, leading to a wide range of symptoms in patients. To better understand how SARS-CoV-2 affects the proteome from cells with different ontologies, this work generated an infectome atlas of 9 cell models, including cells from brain, blood, digestive system, and adipocyte tissue.

Combined Training Improves Gene Expression Related to Immunosenescence in Obese Type 2 Diabetic Individuals.

The aim of this study was to investigate the effects of moderate combined training (CT) on both the gene expression of pro- and anti-inflammatory markers and senescence in the immune system in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue (SAT) of obese middle-aged individuals with type 2 diabetes (T2D). Thirty obese individuals (50.2 ± 9.

Thymic Innervation Impairment in Experimental Autoimmune Encephalomyelitis.

Introduction: The thymus is the primary lymphoid organ responsible for normal T-cell development. Yet, in abnormal metabolic conditions as well as an acute infection, the organ exhibits morphological and cellular alterations. It is well established that the immune system is in a tidy connection and dependent on the central nervous system (CNS), which regulates thymic function by means of innervation and neurotransmitters.

Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome.

Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8 T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis.

Case Presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment.

SARS-CoV-2 uses CD4 to infect T helper lymphocytes.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood.

Defective Induction of IL-27-Mediated Immunoregulation by Myeloid DCs in Multiple Sclerosis.

The purpose of this study was to examine whether myeloid dendritic cells (mDCs) from patients with multiple sclerosis (MS) and healthy controls (HCs) become similarly tolerogenic when exposed to IL-27 as this may represent a potential mechanism of autoimmune dysregulation. Our study focused on natural mDCs that were isolated from HCs and MS patient peripheral blood mononuclear cells (PBMCs). After a 24-h treatment with IL-27 ± lipopolysaccharide (LPS), the mDCs were either harvested to identify IL-27-regulated gene expression or co-cultured with naive T-cells to measure how the treated DC affected T-cell proliferation and cytokine secretion.

Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19.

Background And Aims: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes.

Methods: Individuals hospitalized due to COVID-19 (n = 40) were enrolled.

SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner.

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage.

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain.

Cytotoxic B Cells in Relapsing-Remitting Multiple Sclerosis Patients.

Background: Emerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) pathogenesis.

Objective: To investigate whether CD19 B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8 T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.

Methods: In this study, 104 RRMS patients during different treatments and 58 healthy donors were included.

In silico analysis of mutant epitopes in new SARS-CoV-2 lineages suggest global enhanced CD8+ T cell reactivity and also signs of immune response escape.

SARS-CoV-2 variants of concern have emerged since the COVID-19 outburst, notably the lineages detected in the UK, South Africa, and Brazil. Their increased transmissibility and higher viral load put them in the spotlight. Much has been investigated on the ability of those new variants to evade antibody recognition.

Obesity Increases Gene Expression of Markers Associated With Immunosenescence in Obese Middle-Aged Individuals.

Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18).

Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines.

A SARS-CoV-2 B.1.1.

Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines.

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin.

Decreased Neurofilament L Chain Levels in Cerebrospinal Fluid and Tolerogenic Plasmacytoid Dendritic Cells in Natalizumab-Treated Multiple Sclerosis Patients - Brief Research Report.

Background: Neurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients.

Objective: To evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment.

Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.

Background: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.

Cytotoxic profile of CD3+CD20+ T cells in progressive multiple sclerosis.

Recently, it was shown that highly effective anti-CD20 therapies used for MS patients not only deplete CD20+ B cells, but also a small subset of T cells expressing CD20 surface marker (CD3+CD20+ T cells). Here we demonstrated that, in progressive MS patients, CD3+CD20+ T cells share the ability to express cytotoxic factors such as perforin and serine-protease granzyme-B (GzmB), classically associated with CD8+ T cells functionality. Beyond it, cluster analyses show that a set of activation markers and transcriptional factors related with CD8 effector program are also expressed in CD3+CD20+ T cells.

Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019.

Objectives: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation.

Methods: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers.

Respiratory Viral Shedding in Healthcare Workers Reinfected with SARS-CoV-2, Brazil, 2020.

We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.

Safety and Outcomes Associated with the Pharmacological Inhibition of the Kinin-Kallikrein System in Severe COVID-19.

Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity.

Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples.

Microbiota-derived molecules called short-chain fatty acids (SCFAs) play a key role in the maintenance of the intestinal barrier and regulation of immune response during infectious conditions. Recent reports indicate that SARS-CoV-2 infection changes microbiota and SCFAs production. However, the relevance of this effect is unknown.