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Background: Data on the development of Covid‐19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. Methods: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017–2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID‐care services as retrieved from a national database. Results: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID‐cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID‐specific causes. Conclusions: During the 2017–2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data. [ABSTRACT FROM AUTHOR]

Background: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations. Objectives: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon. Study design: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real‐time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections. Results: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real‐time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission. Conclusion: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use. Highlights: Respiratory viruses are leading cause of ARTI in pediatric cancer patients.Coinfections are common among febrile pediatric cancer patients.RSV was the most common in mono‐ and coinfections among pediatric cancer patients.RSV, PIV, Flu, HCoV are associated with coinfections.Molecular diagnostics permit rapid and sensitive diagnostics and limit antibiotic abuse. [ABSTRACT FROM AUTHOR]

Summary: DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination‐mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV‐associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered the roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies. [ABSTRACT FROM AUTHOR]

Background: Intrathecal synthesis of oligoclonal IgG antibodies against measles virus (MeV), varicella zoster virus (VZV) and herpes simplex virus type-1 (HSV-1) is a characteristic feature multiple sclerosis (MS). Methods: We have used isoelectric focusing-immunoblot to define the clonal patterns of IgG and of IgG antibodies to MeV, VZV and HSV-1 in supernatants of in vitro cultures of peripheral blood lymphocytes (PBL) and cerebrospinal fluid (CSF) cells and in sera and CSF from three patients with MS and three patients with clinically isolated syndromes (CIS) suspective of demyelinating disease. Results: In vitro synthesis of IgG by PBL was not detected in any patient. In contrast , in vitro synthesis by CSF cells of oligoclonal IgG and oligoclonal IgG antibodies to one or two of the three viruses tested was observed in all six patients. The clonal patterns of the in vitro synthesized IgG and virus specific IgG differed to varying extent from those synthesized intrathecally in vivo. However, in each patient, the in vitro and in vivo intrathecally produced antibodies displayed specificity for the same viruses. The addition of B cell activating factor (BAFF) had no effect on the amounts or clonal patterns of either total IgG or virus-specific IgG produced by CSF cells in vitro. Conclusion: Virus specific B cells capable of spontaneous IgG synthesis are clonally expanded in the CSF of patients with MS. The B-cell repertoire in CSF samples is only partially representative of the intrathecal B-cell repertoire. [ABSTRACT FROM AUTHOR]

Cytokines are small secreted molecules, which mediate cross-talk between cells involved in the immune response. Interferons (IFN)s, constitute a class of cytokines with antiviral activities, and the type I IFNs have been ascribed particularly important roles in the innate antiviral response. Type III IFNs (also known as IFN-λ or interleukin 28/29) represent a class of novel cytokines with biological activities similar to the type I IFNs, but seem to have a more specialized role in antiviral defense by exerting host-protection primarily at epithelial surfaces. In this review, we describe the current knowledge on the role of type III IFNs in antiviral defense. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [ABSTRACT FROM AUTHOR]