Performance of CURB-65 in predicting mortality of patients with community-acquired pneumonia in Saudi Arabia

Introduction: Various objective scoring systems were developed to standardize the approach to the designation of severity of community-acquired pneumonia (CAP). There is limited data on the use of CURB-65 among admitted CAP patients in Saudi Arabia.  Methodology: The retrospective study included CAP patients, admitted to a general hospital in Eastern Saudi Arabia. The CURB-65 was extracted from the available medical records. Results: During the study period, from 2013 to 2016, a total of 1786 adults were admitted with a mean age of 63.9 ± 21.7 (range 14-108 years). The majority of the patients (51.7%) had CURB-65 score 0 or 1 followed by the score 2, 3 and 4/5 (29%, 15.2%, and 4.1%, respectively).  The mean CURB-65 was 1.4 ± 1.12 for those who survived and 2.27 ± 1.03 for those who died (p < 0.001). The mean age was 63.01± 21.9 years for survived patients and 75.1 ± 15.58 years for fatal cases (p < 0.001). The overall 30-day crude mortality rate was 7.6%. The mortality rates for CURB-65 scores 0, 1, 2, 3, and 4/5 were 1.8%, 4.3%, 10.2%, 14%, and 21.9%, respectively. Conclusions: The mortality rates of admitted patients with CAP did not differ from those reported in the literature. However, the utilization of CURB-65 score was low and there is a need for wider implementation of pneumonia severity index for patients presenting with CAP

TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3-/- mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell-derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity

Chikungunya virus strains from each genetic clade bind sulfated glycosaminoglycans as attachment factors

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors. However, the specific types of GAGs and potentially other glycans to which CHIKV binds and whether there are strain-specific differences in GAG binding are not fully understood. To identify the types of glycans bound by CHIKV, we conducted glycan microarray analyses and discovered that CHIKV preferentially binds GAGs. Microarray results also indicate that sulfate groups on GAGs are essential for CHIKV binding and that CHIKV binds most strongly to longer GAG chains of heparin and heparan sulfate. To determine whether GAG binding capacity varies among CHIKV strains, a representative strain from each genetic clade was tested. While all strains directly bound to heparin and chondroitin sulfate in enzyme-linked immunosorbent assays (ELISAs) and depended on heparan sulfate for efficient cell binding and infection, we observed some variation by strain. Enzymatic removal of cell surface GAGs and genetic ablation that diminishes GAG expression reduced CHIKV binding and infectivity of all strains. Collectively, these data demonstrate that GAGs are the preferred glycan bound by CHIKV, enhance our understanding of the specific GAG moieties required for CHIKV binding, define strain differences in GAG engagement, and provide further evidence for a critical function of GAGs in CHIKV cell attachment and infection