We characterized virus-neutralization and spike-binding antibody profiles in myeloma patients following monovalent or bivalent-SARS-CoV-2 booster vaccination. Vaccination improves the breadth of binding antibodies but not neutralization activity against current variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.

Blood based traumatic brain injury (TBI) biomarkers offer additional diagnostic, therapeutic, and prognostic utility. While adult studies are robust, the pediatric population is less well studied. We sought to determine whether plasma osteopontin (OPN) and S100B alone or in combination predict mortality, head Computed tomography (CT) findings, as well as 6-month functional outcomes after TBI in children. This is a prospective, observational study between March 2017 and June 2021 at a tertiary pediatric hospital. The sample included children with a diagnosed head injury of any severity admitted to the Emergency Department. Control patients sustained trauma-related injuries and no known head trauma. Serial blood samples were collected at admission, as well as at 24, 48, and 72 h. Patient demographics, acute clinical symptoms, head CT, and 6-month follow-up using the Glasgow outcome scale, extended for pediatrics (GOSE-Peds), were also obtained. The cohort included 460 children (ages 0 to 21 years) and reflected the race and sex distribution of the population served. Linear mixed effect models and logistic regressions were utilized to evaluate the trajectory of biomarkers over time and predictors of dichotomous outcomes. Both OPN and S100B correlated with injury severity based on GCS. S100B and OPN showed lower AUC values (0.59) in predicting positive head CT. S100B had the largest AUC (0.87) in predicting mortality, as well as 6-month outcomes (0.85). The combination of the two biomarkers did not add meaningfully to the model. Our findings continue to support the utility of OPN as a marker of injury severity in this population. Our findings also show the importance of S100B in predicting mortality and 6-month functional outcomes. Continued work is needed to examine the influence of age-dependent neurodevelopment on TBI biomarker profiles in children.

Individuals who are immunocompromised, including patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL), often mount ineffective antibody responses after SARS-CoV-2 vaccination1, 2, 3 and remain at a high risk of severe COVID-19.4 Several monoclonal antibodies against the SARS-CoV-2 spike protein have been developed for prophylaxis or treatment against infection.5 AZD7442 is a combination of 2 such antibodies (tixagevimab and cilgavimab) with a half-life of ∼90 days.6 It received emergency use authorization (EUA) for use as preexposure prophylaxis in patients who are immunocompromised based on the PROVENT trial, which showed a reduced risk of symptomatic infection among patients deemed at risk of inadequate vaccine response or increased viral exposure.7 However, only 7.2% of the participants had cancer, and 3.2% received immunosuppressive therapy. Importantly, PROVENT was conducted before the emergence of the B.1.1.529 (Omicron) variant. Using purified antibodies and/or pseudoviruses, some studies showed that many antibody formulations developed against the original SARS-CoV-2, including AZD7442, lost significant in vitro activity against Omicron variants.8 Additionally, sera from patients who received AZD7442 blocked the binding between the wild-type spike receptor binding domain (RBD) and plates coated with its receptor ACE2 but had minimal efficacy at blocking the binding between Omicron BA.1 RBD and ACE2.9 Reduced efficacy against Omicron variants was observed in patients treated with half-dose AZD7442,10 and ∼10% of AZD7442-treated kidney transplant recipients developed COVID-19 afterwards, with 35.9% of them requiring hospitalization.11 Although these reports raise concerns that AZD7442 has limited efficacy against Omicron variants, the neutralizing activity of full dose AZD7442 against live, contemporary Omicron variants after administration to patients who are immunocompromised remains unknown. We measured the antibody binding and neutralizing activities of plasma from AZD7442-treated patients with NHL/CLL for several live SARS-CoV-2 variants, including Omicron BA.2.75, BA.5, BQ.1.1, and XBB, which are currently in circulation.

Maintaining blood-brain barrier integrity and minimizing neuronal injury are critical components of any therapeutic intervention following ischemic stroke. However, a low level of vitamin D hormone is a risk factor for many vascular diseases including stroke. The neuroprotective effects of 1,25(OH)2D3 (vitamin D) after ischemic stroke have been studied, but it is not known whether it prevents ischemic injury to brain endothelial cells, a key component of the neurovascular unit. We analyzed the effect of 1,25(OH)2D3 on brain endothelial cell barrier integrity and tight junction proteins after hypoxia/reoxygenation in a mouse brain endothelial cell culture model that closely mimics many of the features of the blood-brain barrier in vitro. Following hypoxic injury in bEnd.3 cells, 1,25(OH)2D3 treatment prevented the decrease in barrier function as measured by transendothelial electrical resistance and permeability of FITC-dextran (40 kDa), the decrease in the expression of the tight junction proteins zonula occludin-1, claudin-5, and occludin, the activation of NF-kB, and the increase in matrix metalloproteinase-9 expression. These responses were blocked when the interaction of 1,25(OH) )2D3 with the vitamin D receptor (VDR) was inhibited by pyridoxal 5'-phosphate treatment. Our findings show a direct, VDR-mediated, protective effect of 1,25(OH) )2D3 against ischemic injury-induced blood-brain barrier dysfunction in cerebral endothelial cells.

Objective: To examine levels of plasma osteopontin (OPN), a recently described neuroinflammatory biomarker, in children with abusive head trauma (AHT) compared with children with other types of traumatic brain injury (TBI). Study design: The study cohort comprised children aged <4 years diagnosed with TBI and seen in the intensive care unit in a tertiary children's hospital. Patients were classified as having confirmed or suspected AHT or TBI by other mechanisms (eg, motor vehicle accidents), as identified by a Child Protection Team clinician. Serial blood samples were collected at admission and at 24, 48, and 72 hours after admission. Levels of OPN were compared across groups. Results: Of 77 patients identified, 24 had confirmed AHT, 12 had suspected AHT, and 41 had TBI. There were no differences in the Glasgow Coma Scale score between the patients with confirmed AHT and those with suspected AHT and those with TBI (median score, 4.5 vs 4 and 7; P =.39). At admission to the emergency department, OPN levels were significantly higher in children with confirmed AHT compared with the other 2 groups (mean confirmed AHT, 471.5 ng/mL; median suspected AHT, 322.3 ng/mL; mean TBI, 278.0 ng/mL; P =.03). Furthermore, the adjusted mean trajectory levels of OPN were significantly higher in the confirmed AHT group compared with the other 2 groups across all subsequent time points (P = <.01). Conclusions: OPN is significantly elevated in children with confirmed AHT compared with those with suspected AHT and those with other types of TBI. OPN expression may help identify children with suspected AHT to aid resource stratification and triage of appropriate interventions for children who are potential victims of abuse.