What Is Baseline? Collegiate Students In High-Stress Settings: A Concussion Policy Analysis

Background: Concussion symptoms are nonspecific and may be related to other causes. Recovery expectations and timing of return to activity after a concussion are areas of the literature with lack of concrete, reproducible data. Symptom scores and timeline of return to activity at many institutions are based on having no symptoms at baseline with the current measurement tools. This assumption in the diagnosis and treatment of concussions may lead to prolonged return to activity, compounded concussion symptoms, and have unintended psychological and social sequelae. More baseline data is needed, according to the CARE Consortium Study which had over 27,000 collegiate participants, especially in military academies. Local problem: During the high-stress initial training period at one mid-Atlantic military college, a no-symptom baseline is unlikely for first-year cadets. The potential overlap of concussion and typical baseline symptoms make diagnosis and release to activity a challenge for providers. On average, it takes two to three weeks longer for a first-year cadet to be fully cleared from a concussion in comparison to the rest of the student body. While it is typical to err in the overtreatment of concussions, prolonged diagnosis and delayed return to activities during this training period anecdotally correlates with psychological distress and higher attrition rates. Methods: A baseline survey of first-year, non-concussed cadets was distributed in fall of 2018 over seven consecutive days to gather normative data for the symptom portion of the Sport Concussion Assessment Tool (SCAT 5). The goal for sample size was a 20% participation rate from first-year cadets. Data will be used to develop the status quo of baseline at the college which will inform a policy analysis using Bardach’s Eight-fold Path. Policies from similar institutions will be compared using the Development Assistance Committee (DAC) evaluation criteria. If 50% of first year cadets have symptoms at baseline, policy change will be considered. Results: 139 cadets responded to all seven days of the baseline survey, and the day of highest participation received 214 responses. Data analysis will continue throughout the spring of 2019. Implications: Pending the results of the survey and policy analysis, it is likely that a policy change will be considered. Further research is warranted to assure safety and efficacy. This military college’s baseline results are likely not isolated. Other military institutions and collegiate settings may want to consider development of normative baseline symptomatology to better inform their policy decisions

Best Paper Finalist Session 2 Recording

Discussant: Adam Vanhove, James Madison University Chair: Brian Smallwood, James Madison University Through the Fire Again: Using Derailment Research to Lead Change in the COVID-19 Era Jeff Strietzel, Baylor University Ryan Erck, Baylor University Presentation Slides A Rural Perspective on COVID Responses: Access, Interdependence, and Community Margaret F. Sloan, James Madison University Laura Hunt Trull, James Madison University Maureen Malomba, James Madison University Emily Akerson, James Madison University Kelly Atwood, James Madison University Melody Eaton, James Madison University University Administrators Serving International Students During Social and Organizational Change Luda Patokina, Hofstra University Presentation Slide

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56dimCD57+ natural killer (NK) cells and exhausted CD8+ T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8+ T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health