Toll-like receptors, chemokine receptors and death receptor ligands responses in SARS coronavirus infected human monocyte derived dendritic cells

<p>Abstract</p> <p>Background</p> <p>The SARS outbreak in 2003 provides a unique opportunity for the study of human responses to a novel virus. We have previously reported that dendritic cells (DCs) might be involved in the immune escape mechanisms for SARS-CoV. In this study, we focussed on the gene expression of toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in SARS-CoV infected DCs. We also compared adult and cord blood (CB) DCs to find a possible explanation for the age-dependent severity of SARS.</p> <p>Results</p> <p>Our results demonstrates that SARS-CoV did not modulate TLR-1 to TLR-10 gene expression but significantly induced the expression of CCR-1, CCR-3, and CCR-5. There was also strong induction of TNF-related apoptosis-inducing ligand (TRAIL), but not Fas ligand gene expression in SARS-CoV infected DCs. Interestingly, the expressions of most genes studied were higher in CB DCs than adult DCs.</p> <p>Conclusion</p> <p>The upregulation of chemokines and CCRs may facilitate DC migration from the infection site to the lymph nodes, whereas the increase of TRAIL may induce lymphocyte apoptosis. These findings may explain the increased lung infiltrations and lymphoid depletion in SARS patients. Further explorations of the biological significance of these findings are warranted.</p

Impact of respiratory viruses on mortality

published_or_final_versionMedical SciencesMasterMaster of Medical Science

Clinical Outcome and Complications of Transpedicular Closing-wedge Osteotomy for Correction of Deformity in Ankylosing Spondylitis in a Regional Hospital

Study design: Prospective study of surgical correction of thoracolumbar kyphotic deformity caused by ankylosing spondylitis. Objectives: To assess surgical outcomes and complications of thoracolumbar kyphotic deformity corrected with transpedicular closing-wedge osteotomy performed in a regional hospital. Summary of background data: There have been several studies reporting on the results of surgical correction of deformity in ankylosing spondylitis all over the world. However, there has not been any local data published. Methods: From 2003 to 2011, we had performed 12 transpedicular closing-wedge osteotomies in 9 patients with ankylosing spondylitis for correction of kyphotic and scoliotic deformity in thoracolumbar spine. Operative outcomes were assessed clinically by recording the Japanese Orthopaedic Association (JOA) scores, visual analogue scale (VAS) pain scores, Oswestry Disability Index (ODI) preoperatively and postoperatively and patient satisfaction postoperatively. Radiological outcome was assessed by measuring thoracic kyphosis, lumbar lordosis and sagittal plumb line preoperatively and postoperatively as well as the degree of surgical correction. Occurrence of complications was recorded by our standard audit protocol. Results: All patients had a single level of osteotomy done at a time. Most of the osteotomies were done at L2 or L3. The mean amount of correction was 21.6°. Complications included dural tear, pseudoarthrosis and transient radiculopathy. The extent of correction and incidence of complications improved with experience. Conclusion: Despite transpedicular closing-wedge osteotomy being a major operation that is not without complications, most of our patients had good clinical results and subjective satisfaction

Chemokine up-regulation in SARS-coronavirus–infected, monocyte-derived human dendritic cells

Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV–infected DCs. The SARS-CoV–infected DCs showed low expression of antiviral cytokines (interferon α [IFN-α], IFN-β, IFN-γ, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor α [TNF-α] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1α [MIP-1α], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV

The clinical characteristics of pediatric patients infected by SARS-CoV-2 Omicron variant and whole viral genome sequencing analysis.

Pediatric population was generally less affected clinically by SARS-CoV-2 infection. Few pediatric cases of COVID-19 have been reported compared to those reported in infected adults. However, a rapid increase in the hospitalization rate of SARS-CoV-2 infected pediatric patients was observed during Omicron variant dominated COVID-19 outbreak. In this study, we analyzed the B.1.1.529 (Omicron) genome sequences collected from pediatric patients by whole viral genome amplicon sequencing using Illumina next generation sequencing platform, followed by phylogenetic analysis. The demographic, epidemiologic and clinical data of these pediatric patients are also reported in this study. Fever, cough, running nose, sore throat and vomiting were the more commonly reported symptoms in children infected by Omicron variant. A novel frameshift mutation was found in the ORF1b region (NSP12) of the genome of Omicron variant. Seven mutations were identified in the target regions of the WHO listed SARS-CoV-2 primers and probes. On protein level, eighty-three amino acid substitutions and fifteen amino acid deletions were identified. Our results indicate that asymptomatic infection and transmission among children infected by Omicron subvariants BA.2.2 and BA.2.10.1 are not common. Omicron may have different pathogenesis in pediatric population