Von Willebrand factor (vWF): marker of endothelial damage and thrombotic risk in COVID-19?

BACKGROUND: COVID-19 infection is characterised, among other features, by a prothrombotic state with high rate of venous thromboembolism (VTE), D-dimer, and fibrinogen levels. Clinical observations have also highlighted that these patients have elevated von Willebrand factor (vWF) and factor VIIIc. METHODS: 24 consecutive COVID-19 positive patients were selected from the intensive care unit (ICU) or the high acuity ward of Brighton and Sussex University Hospitals NHS Trust. RESULTS: The rate of VTE was 25% and mortality rate was 16.7%. Fibrinogen and D-Dimers were elevated, 7.9 (1.6) g/L and 2.4 (2.02) ug/ml respectively. Factor VIIIc and von vWF antigen levels were both extremely elevated at 279 (148) u/dL and 350 (131) % respectively, which are comparable to levels seen in ICU patients with severe sepsis. vWF levels were significantly higher in patients that died (p=0.017) and showed a positive correlation with age. There was a statistically significant association between COVID-19 disease and non-O blood group (p=0.02); 80% (4/5) of COVID-19 patients with VTE were blood group A. CONCLUSION: Very high levels of vWF and factor VIIIc are common in COVID-19 patients, comparable to levels in severely septic non-COVID ICU patients. This could contribute to the hypercoagulable state and increased VTE rate in COVID-19. Further studies are needed to evaluate the use of vWF for stratifying thrombotic risk in COVID-19 and to determine if elevated vWF is contributing to disease pathogenesis.

Management of suspected paediatric meningitis: a multicentre prospective cohort study.

OBJECTIVE: To quantify delays during management of children with suspected meningitis. DESIGN: Multicentre prospective cohort study. SETTING: Three UK tertiary paediatric centres; June 2011-June 2012 PATIENTS: 388 children aged <16 years hospitalised with suspected meningitis or undergoing lumbar puncture (LP) during sepsis evaluation. MAIN OUTCOME MEASURES: Time of prehospital and in-hospital assessments, LP, antibiotic treatment and discharge; types of prehospital medical assessment and microbiological results. Data collected from hospital records and parental interview. RESULTS: 220/388 (57%) children were seen by a medical professional prehospitalisation (143 by a general practitioner). Median times from initial hospital assessment to LP and antibiotic administration were 4.8 hours and 3.1 hours, respectively; 62% of children had their LP after antibiotic treatment. Median time to LP was shorter for children aged <3 months (3.0 hours) than those aged 3-23 months (6.2 hours, P<0.001) or age ≥2 years (20.3 hours, P<0.001). In meningitis of unknown cause, cerebrospinal fluid (CSF) PCR was performed for meningococcus in 7%, pneumococcus in 10% and enterovirus in 76%. When no pathogen was identified, hospital stay was longer if LP was performed after antibiotics (median 12.5 days vs 5.0 days, P=0.037). CONCLUSIONS: Most children had LP after antibiotics were administered, reducing yield from CSF culture, and PCRs were underused despite national recommendations. These deficiencies reduce the ability to exclude bacterial meningitis, increasing unnecessary hospital stay and antibiotic treatment.

Natural immunity against capsular group X N. meningitidis following an outbreak in Togo, 2007.

BACKGROUND: Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in individuals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy individuals (100 aged 3-5 years, 100 aged 13-19 years and 100 aged 20-25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. METHODS: MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. RESULTS: The proportion of Togolese individuals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18-41) among those aged 3-5 years, 34% (95% CI 9-60) among those aged 13-19 years and 32% (95% CI 24-40) among those aged 20-25 years. These were significantly higher than observed in the control populations from the U.K (range 13-16%) and Burkina Faso (range 2-6%). CONCLUSION: In Togolese individuals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.