SARS-CoV-2 Vaccine-Elicited Immunity after B Cell Depletion in Multiple Sclerosis.

The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

Patterns of on-scene and healthcare system trauma deaths in the Western Cape of South Africa.

BACKGROUND: Injuries account for 8% or 4.4 million deaths annually worldwide, with 90% of injury deaths occurring in low- and middle-income countries. Inter-personal violence and road traffic injuries account for most injury deaths in South Africa, with rates among the highest globally. Understanding the location, timing, and factors of trauma deaths can identify opportunities to strengthen care. METHODS: This is a retrospective cross-sectional secondary analysis of trauma deaths from 2021 to 2022 in the Western Cape of South Africa. Healthcare system trauma deaths were identified from a multicenter study paired with a dataset for on-scene (i.e., prior to ambulance or hospital) trauma deaths in the same jurisdictions. We describe locations, timing, injury factors, and cause of death. We assess associations between those factors. RESULTS: There were 2418 deaths, predominantly young men, with most (2274, 94.0%) occurring on-scene. The most frequent mechanism of injury for all deaths was firearms (32.6%), followed by road traffic collisions (17.8%). On-scene deaths (33.2%) were significantly more likely to be injured by firearms compared to healthcare system deaths (23.6%) (p-value <0.01). Most healthcare system deaths within 4-24 h of injury occurred in a hospital emergency center. Among healthcare system decedents, half died in the emergency unit. CONCLUSIONS: We identified a large burden of deaths from interpersonal violence and road traffic collisions, mostly on-scene. In addition to primary prevention, shortening delays to care can improve mortality outcomes especially for deaths occurring within 4-24 h in emergency centers.

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed-Methods Study.

OBJECTIVE: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods. METHODS: Individuals with ACPA positivity without IA were provided information regarding their risk for future RA, were provided a description of a clinical prevention trial using hydroxychloroquine, and were asked if they would participate in the trial. After agreeing to or declining participation, they were surveyed on what influenced their decision using Likert scales and open-response questions. RESULTS: Thirty-nine individuals who agreed to trial participation (enrollees) and 31 individuals who declined (nonenrollees) completed surveys. Enrollees expressed greater perceived risk for RA and greater perception of benefit to themselves or others than nonenrollees. Nonenrollees expressed greater concern about medication effects and less personal or family experience with RA than enrollees. There was a higher proportion of first-degree relatives (FDRs) of people with RA in enrollees versus nonenrollees (54% vs. 23%, P = 0.01). CONCLUSION: Enrollees were more likely than nonenrollees to be FDRs, exhibit stronger concern for personal risk for RA, and have less concern about adverse effects. Further exploration is needed to determine why these differences were present, including exploration of symptoms and the role of family history. Understanding these issues will better inform researchers and individuals who are candidates for prevention.