Clinical Practice Guideline-Supported Administration of Monoclonal Antibody Therapy for High-Risk Patients with COVID-19: Experience of a Quaternary Care Centre.

Background: Immunocompromised patients remain at risk of progression to severe COVID-19 disease.

Methods: We describe clinical COVID-19-related outcomes after administration of anti-SARS-CoV-2 monoclonal antibodies (mAb) following institutional clinical practice guidelines (CPGs) in 205 high-risk patients between November 2021 and April 2022 at a Canadian quaternary care centre.

Results: Median patient age was 59 years; 102 (50%) were female.

Machine Learning Accurately Predicts Need for Critical Care Support in Patients Admitted to Hospital for Community-Acquired Pneumonia.

Objectives: Hospitalized community-acquired pneumonia (CAP) patients are admitted for ventilation, vasopressors, and renal replacement therapy (RRT). This study aimed to develop a machine learning (ML) model that predicts the need for such interventions and compare its accuracy to that of logistic regression (LR).

Design: This retrospective observational study trained separate models using random-forest classifier (RFC), support vector machines (SVMs), Extreme Gradient Boosting (XGBoost), and multilayer perceptron (MLP) to predict three endpoints: eventual use of invasive ventilation, vasopressors, and RRT during hospitalization.

A CARD9 deficiency mouse model recapitulates human chronic CNS candidiasis identifying defective monocytic cell responses in immunopathogenesis.

Human Caspase Recruitment Domain Containing Protein 9 (CARD9) deficiency predisposes to invasive fungal disease, particularly by Candida spp. CARD9 deficiency causes chronic central nervous system (CNS) candidiasis. Currently, no animal model recapitulates the chronicity of disease, precluding a better understanding of immunopathogenesis.

Host-directed immunotherapy for viral infections.

Purpose Of Review: The limitations of pathogen-directed therapies include growing antimicrobial resistance or the complete lack of any effective antimicrobial agents. This review highlights the potential for host-directed immunotherapies.

Recent Findings: This review provides a current status of host-directed immunotherapies to fight infectious diseases (HIFI), defining the concept and existing modalities.

A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection.

Type 1 immunity mediates host defense through pathogen elimination, but whether this pathway also impacts tissue function is unknown. Here, we demonstrate that rapid induction of interferon γ (IFNγ) signaling coordinates a multicellular response that is critical to limit tissue damage and maintain gut motility following infection of mice with a tissue-invasive helminth. IFNγ production is initiated by antigen-independent activation of lamina propria CD8 T cells following MyD88-dependent recognition of the microbiota during helminth-induced barrier invasion.

Human immunity to fungal infections.

Fungi increasingly threaten health globally. Mycoses range from life-threatening, often iatrogenic conditions, to enigmatic syndromes occurring without apparent immunosuppression. Despite some recent advances in antifungal drug development, complementary therapeutic strategies are essential for addressing these opportunistic pathogens.

Leaky Artemis Deficiency and EBV-Related Lymphoproliferative Disease: A Novel Case and Review of the Literature.

Introduction: Artemis () deficiency causes radiosensitive severe combined immunodeficiency (SCID), although hypomorphic cases can manifest later-onset immunodeficiency, autoimmunity, or lymphoproliferation. We report a 45-year-old man with humoral immunodeficiency, opportunistic infections, and recurrent EBV-positive diffuse large B-cell lymphoma (DLBCL).

Methods: Genetic analysis was performed to identify mutations in the gene.

Two rare mutations in homozygosity synergize to silence TREX1 in Aicardi-Goutières syndrome.

Background: Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy characterized by dysregulated inflammation and tissue damage that primarily affects the central nervous system. AGS is genetically diverse, with pathogenic variants across multiple genes, including TREX1, which drives excessive type I interferon (IFN) production.

Objective: This study investigated the genetic and molecular mechanisms underlying AGS in a family of two affected children, focusing on the role of variants in protein expression and dysregulation of the interferon pathway.

Neuropsychiatric Symptoms and Psychotropic Medication Use Following SARS-Cov-2 Infection Among Elderly Residents in Long-Term Care Facilities.

Background: SARS-CoV-2 infection can lead to persistent post-acute neuropsychiatric symptoms. Older adults with multimorbidity may be at increased risk of post-acute symptoms after COVID-19. The goals of the present study were to assess the associations of SARS-CoV-2 infection with neuropsychiatric symptoms and psychotropic medication prescription among older adults living in long-term care facilities.

Global guideline for the diagnosis and management of candidiasis: an initiative of the ECMM in cooperation with ISHAM and ASM.

Candida species are the predominant cause of fungal infections in patients treated in hospital, contributing substantially to morbidity and mortality. Candidaemia and other forms of invasive candidiasis primarily affect patients who are immunocompromised or critically ill. In contrast, mucocutaneous forms of candidiasis, such as oral thrush and vulvovaginal candidiasis, can occur in otherwise healthy individuals.

Humoral and cell-mediated immune responses to COVID-19 vaccines up to 6 months post three-dose primary series in adults with inborn errors of immunity and their breakthrough infections.

Purpose: Many individuals with inborn errors of immunity (IEIs) have poor humoral immune (HI) vaccine responses. Only a few studies have examined specific cell-mediated immune (CMI) responses to coronavirus disease 2019 (COVID-19) vaccines in this population. Therefore, the purpose of this study was to examine HI and CMI responses up to 6 months post-COVID-19 vaccine dose 3 in adults with IEIs.

Respiratory Viruses in Patients With Hematological Malignancy in Boreal Autumn/Winter 2023-2024: EPICOVIDEHA-EPIFLUEHA Report.

Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

Community versus academic hospital community-acquired pneumonia patients: a nested cohort study.

Background: Most Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes.

Methods: This nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals.

From Mendel to mycoses: Immuno-genomic warfare at the human-fungus interface.

Fungi are opportunists: They particularly require a defect of immunity to cause severe or disseminated disease. While often secondary to an apparent iatrogenic cause, fungal diseases do occur in the absence of one, albeit infrequently. These rare cases may be due to an underlying genetic immunodeficiency that can present variably in age of onset, severity, or other infections, and in the absence of a family history of disease.

A Novel Homozygous Mutation Causing Complete TYK2 Deficiency, with Severe Respiratory Viral Infections, EBV-Driven Lymphoma, and Jamestown Canyon Viral Encephalitis.

Autosomal recessive tyrosine kinase 2 (TYK2) deficiency is characterized by susceptibility to mycobacterial and viral infections. Here, we report a 4-year-old female with severe respiratory viral infections, EBV-driven Burkitt-like lymphoma, and infection with the neurotropic Jamestown Canyon virus. A novel, homozygous c.

Outcomes and characteristics of patients hospitalized for COVID-19 in British Columbia, Ontario and Quebec during the Omicron wave.

Background: Omicron is the current predominant variant of concern of SARS-CoV-2. We hypothesized that vaccination alters outcomes of patients hospitalized with COVID-19 during the Omicron wave and that these patients have different characteristics and outcomes than in previous waves.

Methods: This is a substudy of the Host Response Mediators in Coronavirus (COVID-19) Infection (ARBs CORONA I) trial, which included adults admitted to hospital with acute COVID-19 up to July 2022 from 9 hospitals in British Columbia, Ontario and Quebec.

Recommendations for Management of Secondary Antibody Deficiency in Multiple Myeloma.

Secondary antibody deficiency (SAD) is a subtype of secondary immunodeficiency characterized by low serum antibody concentrations (hypogammaglobulinemia) or poor antibody function. SAD is common in patients with multiple myeloma (MM) due to underlying disease pathophysiology and treatment-related immune system effects. Patients with SAD are more susceptible to infections and infection-related morbidity and mortality.

A Novel Mutation Leading to Wiskott-Aldrich Syndrome in an Ethiopian Boy: a Case Report and a Review of Literature.

Wiskott-Aldrich syndrome is an X-linked recessive primary immune-deficiency disorder very rarely reported from black African children. A 12-year old boy with recurrent sinopulmonary and diarrheal infections, eczema, thrombocytopenia, and low platelet volume was found by whole genome sequencing to harbor a predicted pathogenic c.1205dupC (p.