The Infant Transcriptome in Meningococcal Septic Shock: A Force in Precision Cellular Dysfunction Suggesting a Cytokine Storm?

BACKGROUND AND AIM: The ideal biomarker(s) to track evolution and the underlying basis of sepsis remain elusive. We hypothesized that assessing differential mRNA gene expression may aid in tracking sepsis pathogenesis in infants with meningococcal septic shock (MSS). METHOD(S): Temporal paediatric gene expression datasets from Meningococcal Group B sepsis studies in the United Kingdom (MSS1, 29 samples) and Holland (MSS2, 41 samples) underwent Principal Component Analysis (PCA) and Gene Set Enrichment Analysis (GSEA). RESULT(S): Gene-expression clustering algorithm for both datasets demonstrated a baseline state on admission, an intermediate state, and a final state. Additionally, PCA plots suggested a gene-expression trajectory. The MSS1 study showed that 410 genes differentiated survivors from a nonsurvivor, including the ICAM-3 gene. Moreover GSEA t-Test identified apoptosis to be significantly differently (p = 0.02 and q = 0.15) associated with the fatal case compared to the four survivors in MSS1. Also in MSS1, we identified a genesignature for cytokine production which included 5 genes (CLC, HFE, HLA-F, NLRP3, TNFRSF1B) from the cytokine GSEA gene panel. The genes NLRP3 and TNFRSF1B have been noted in the cytokine storm of Coronavirus infection. Also Transcript Time Course Analysis (TTCA) confirmed differential gene function associated with Coronavirus. CONCLUSION(S): Transcriptomic analysis in two independent datasets in infants with MSS identified a trajectorial pattern. Further, the transcriptome expression differed between survivors and non-survivors, suggesting differences in cytokine signalling. Including the existence of genes associated with the cytokine storm of SARS-CoV2. The exploitability of transcriptome analysis to guide therapy and prognosis requires further investigation. (Figure Presented).

In-Vitro and in-Vivovascular Endothelial Growth Factor Subtypes a & B in Severe Acute Respiratory Syndrome Pathogenesis

BACKGROUND AND AIM: Increased Vascular Endothelial Growth Factor (VEGFA) Gene Expression (GE) has been documented in SARS-CoV2 infection. We wished to understand the relationship of VEGFA and VEGF B GE in both Murine SARS-CoV and Human SARS-CoV-2 in-vitro models of infection. METHOD(S): Secondary analysis of datasets from mice given nasal installation of SARS-CoV (MA15), MS1 (GSE33266MCV-1) and MS2 (GSE68820) from pulmonary tissues was undertaken. This allowed viral dose and temporal response analysis, respectively. Also studied were In-vitro Human hACE2 cells infected with SARS-CoV2 (dataset INV, GSE169158). Gene expression (GE) VEGF sub-types were analysed using Qlucore Omics Explorer (QOE) and gene enrichment functional profiling through the g:Profiler online platform. RESULT(S): For Murine studies, MA15 instillation compared to controls in MS1, lead to down-regulation of both VEGFB (MA15 10

Abnormal pupillary light reflex responses in post-COVID-19 patients

Purpose: Neurological manifestations involving the central, peripheral, and autonomic nervous system have been reported in the acute phase of coronavirus disease 2019 (COVID-19) and have been shown to persist in a proportion of patients after recovery. In this cross-sectional study, we assessed pupillary light reflex responses using dynamic pupillometry in patients after COVID-19. Methods: Thirty patients recovered from COVID-19 and 25 healthy control participants were studied using an infrared dynamic pupillometry system (MonPack One;Metrovision, France) to quantify pupillary responses to white light stimulation (light intensity 100 cd/m2, on/off time 200/3300 ms) (Figure 1). A questionnaire in accord with the long-COVID guideline developed by the National Institute for Health and Care Excellence (NICE) was used to identify persisting symptoms more than 4 weeks. Patients with diabetes mellitus or any other systemic disease that might cause autonomic dysfunction were excluded. Results: Post-COVID-19 patients and control participants were matched for age (P=0.179) and gender (P=0.522). The mean time after the diagnosis of COVID-19 was 3.6 ± 1.6 months. There was no significant difference in the initial pupil diameter, amplitude and velocity of pupil contraction, and latency, duration and velocity of pupil dilation, but the latency of pupil contraction was increased (P <0.001) and the duration of pupil contraction was reduced (P=0.029) in post-COVID-19 patients compared to healthy controls. Amongst patients with COVID-19, 16/30 (53%) had at least one persisting neurological symptom beyond 4 weeks after infection. Compared to controls, the latency of pupil contraction was increased in both subgroups of patients with (P=0.014) and without (P <0.001) persisting neurological symptoms. However, the duration of contraction was reduced only in the subgroup of subjects with neurological symptoms (P=0.025). NICE questionnaire score correlated with the duration of contraction (p=-0.366;P=0.030), the latency of dilation (p=-0.411;P=0.024), and the duration of dilation (p=0.381;P=0.038). Conclusions: Dynamic pupillometry demonstrates significant alterations in pupillary light responses in post-COVID-19 patients, particularly those with persisting neurological symptoms.

COVID-19 infection is related to differences in the use of personal protective equipment by orthopaedic specialist trainees caring for hip fracture patients during the second surge of COVID-19 in the North West of England.

INTRODUCTION: Personal protective equipment (PPE) may protect health-care workers from COVID-19 infection and limit nosocomial spread to vulnerable hip fracture patients. METHODS: We performed a cross-sectional survey amongst orthopaedic trainees to explore PPE practice in 19 hospitals caring for hip fracture patients in the North West of England. RESULTS: During the second wave of the pandemic, 14/19 (74%) hospitals experienced an outbreak of COVID-19 amongst staff or patients on the orthopaedic wards. An FFP3 respirator mask was used by doctors in only 6/19 (32%) hospitals when seeing patients with COVID-19 and a cough and in 5/19 (26%) hospitals when seeing asymptomatic patients with COVID-19. A COVID-19 outbreak was reported in 11/13 (85%) orthopaedic units where staff wore fluid resistant surgical masks compared to 3/6 (50%) units using an FFP3 respirator mask (RR 1.69, 95% CI 0.74-3.89) when caring for symptomatic patients with COVID-19. Similarly, a COVID-19 outbreak was reported in more orthopaedic units caring for asymptomatic patients with COVID-19 where staff wore fluid resistant surgical masks (12/14 (86%)) as compared to an FFP3 respirator mask (2/5 (40%)) (RR 2.14, 95% CI 0.72-6.4). CONCLUSION: Urgent re-evaluation of PPE use is required to reduce nosocomial spread of COVID-19, amongst highly vulnerable patients with hip fracture.

Limited implementation of measures to reduce nosocomial spread of COVID-19 in hip-fracture patients in the North West of England.

Hip-fracture patients are vulnerable to the outcomes of COVID-19. We performed a cross-sectional survey to determine measures employed to limit nosocomial spread of COVID-19 in 23 orthopaedic trauma departments in the North-West of England. Nineteen (87%) hospitals admitted patients to a ward prior to a negative swab, and only 9 (39%) patients were barrier nursed. Hip-fracture patients were operated in non-COVID-19-free theatres in 21 (91%) hospitals. Regular screening of doctors working in trauma and elective areas for COVID-19 was undertaken in three (13%) and five (22%) hospitals, respectively. Doctors moved freely between trauma and elective areas in 22 (96%) hospitals.