Humoral and Cellular Immune Response to Covid-19 Vaccination in Patients with Chronic Graft-versus-Host Disease on Immunosuppression.

Chronic graft-versus-host disease (cGVHD) and its management with immunosuppressive therapies increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as progression to severe Coronavirus 19 disease (COVID-19). Vaccination against COVID-19 is strongly recommended, but efficacy data are limited in this patient population. In this study, responses to COVID-19 vaccination were measured at 3 time points-after the initial vaccine series, before the third dose, and after the third dose-in adults with cGVHD receiving immunosuppressive therapy. Humoral response was measured by quantitative anti-spike antibody and neutralizing antibody levels. Anti-nucleocapsid antibody levels were measured to detect natural infection. T cell response was evaluated by a novel immunosequencing technique combined with immune repertoire profiling from cryopreserved peripheral blood mononuclear cell samples. Present or absent T cell responses were determined by the relative proportion of unique SARS-CoV-2-associated T cell receptor sequences ("breadth") plus clonal expansion of the response ("depth") compared with those in a reference population. Based on both neutralizing antibody and T cell responses, patients were categorized as vaccine responders (both detected), nonresponders (neither detected), or mixed (one but not both detected). Thirty-two patients were enrolled for the initial series, including 17 (53%) positive responders, 7 (22%) mixed responders, and 8 (25%) nonresponders. All but one patient categorized as mixed responders had humoral responses while lacking T cell responses. No statistical differences were observed in patient characteristics among the 3 groups of patients categorized by immune response, although sample sizes were limited. Significant positive correlations were observed between the robustness of cellular and humoral responses after the initial series. Among the 20 patients with paired samples (pre- and post-third dose), a third vaccination resulted in increased neutralizing antibody titers. cGVHD worsened in 10 patients (26%; 6 after the initial series and 4 after the third dose), necessitating escalation of immunosuppressive doses in 5 patients, although 4 had been tapering immunosuppression and 5 had already worsening cGVHD at the time of vaccination, and a clear association between COVID-19 vaccination and cGVHD could not be drawn. Among the patients with cGVHD on immunosuppressive therapy, 72% demonstrated a neutralizing antibody response after a 2-dose primary COVID-19 vaccination, two-thirds of whom also developed a T cell response; 25% had neither a humoral nor a T cell response. A third dose further amplified the antibody response.

A Computerized Cognitive Test Battery for Detection of Dementia and Mild Cognitive Impairment: Instrument Validation Study.

BACKGROUND: Early detection of dementia is critical for intervention and care planning but remains difficult. Computerized cognitive testing provides an accessible and promising solution to address these current challenges. OBJECTIVE: The aim of this study was to evaluate a computerized cognitive testing battery (BrainCheck) for its diagnostic accuracy and ability to distinguish the severity of cognitive impairment. METHODS: A total of 99 participants diagnosed with dementia, mild cognitive impairment (MCI), or normal cognition (NC) completed the BrainCheck battery. Statistical analyses compared participant performances on BrainCheck based on their diagnostic group. RESULTS: BrainCheck battery performance showed significant differences between the NC, MCI, and dementia groups, achieving 88% or higher sensitivity and specificity (ie, true positive and true negative rates) for separating dementia from NC, and 77% or higher sensitivity and specificity in separating the MCI group from the NC and dementia groups. Three-group classification found true positive rates of 80% or higher for the NC and dementia groups and true positive rates of 64% or higher for the MCI group. CONCLUSIONS: BrainCheck was able to distinguish between diagnoses of dementia, MCI, and NC, providing a potentially reliable tool for early detection of cognitive impairment.