Multiparametric MRI Changes Persist Beyond Recovery in Concussed Adolescent Hockey Players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial

OBJECTIVES:. To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19). DESIGN:. Double-blind, randomized clinical trial. SETTING:. Two ICUs at an academic medical center. PATIENTS/SUBJECTS:. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support. INTERVENTIONS:. SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days. MEASUREMENTS AND MAIN RESULTS:. We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial. LIMITATIONS:. The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial. CONCLUSIONS:. Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis

Detection and Profiling of Human Coronavirus Immunoglobulins in Critically Ill Coronavirus Disease 2019 Patients

Objectives:. Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response. Design:. Blood was collected at predetermined ICU days to measure immunoglobulin G with a research multiplex assay against four severe acute respiratory syndrome coronavirus 2 proteins/subunits and against all six additionally known human coronaviruses. Setting:. Tertiary care ICU and academic laboratory. Subjects:. ICU patients suspected of being infected with severe acute respiratory syndrome coronavirus 2 had blood collected until either polymerase chain reaction testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until death or discharge if the patient tested polymerase chain reaction positive (coronavirus disease 2019 positive). Interventions:. None MEASUREMENTS AND MAIN RESULTS:. Age- and sex-matched healthy controls and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients had greater body mass indexes, presented with bilateral pneumonias more frequently, and suffered lower Pao2:Fio2 ratios, when compared with coronavirus disease 2019 negative patients (p < 0.05). Mortality rate for coronavirus disease 2019 positive patients was 50%. On ICU days 1–3, anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G was significantly elevated in coronavirus disease 2019 positive patients, as compared to both healthy control subjects and coronavirus disease 2019 negative patients (p < 0.001). Weak severe acute respiratory syndrome coronavirus immunoglobulin G serologic responses were also detected, but not other coronavirus subtypes. The four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G were maximal by ICU day 3, with all four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G providing excellent diagnostic potential (severe acute respiratory syndrome coronavirus 2 Spike 1 protein immunoglobulin G, area under the curve 1.0, p < 0.0005; severe acute respiratory syndrome coronavirus receptor binding domain immunoglobulin G, area under the curve, 0.93–1.0; p ≤ 0.0001; severe acute respiratory syndrome coronavirus 2 Spike proteins immunoglobulin G, area under the curve, 1.0; p < 0.0001; severe acute respiratory syndrome coronavirus 2 Nucleocapsid protein immunoglobulin G area under the curve, 0.90–0.95; p ≤ 0.0003). Anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G increased and/or plateaued over 10 ICU days. Conclusions:. Critically ill coronavirus disease 2019 patients exhibited anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G, whereas serologic responses to non–severe acute respiratory syndrome coronavirus 2 antigens were weak or absent. Detection of human coronavirus immunoglobulin G against the different immunogenic structural proteins/subunits with multiplex assays may be useful for pathogen identification, patient cohorting, and guiding convalescent plasma therapy