Suchergebnisse

BACKGROUND: While the majority of illness due to COVID-19 does not require hospitalization, little has been described about the host inflammatory response in the ambulatory setting. Differences in the levels of inflammatory signaling proteins between outpatient and hospitalized populations could identify key maladaptive immune responses during COVID-19. METHODS: Samples were collected from 76 participants (41% female, mean 46.8 years of age) enrolled at five military treatment facilities between March 20, 2020 and June 17, 2020 in an ongoing prospective COVID-19 cohort. This analysis was restricted to those with positive SARS-CoV-2 (severe acute respiratory syndrome–coronavirus 2) RT-PCR testing and included hospitalized (N=29; 10 requiring an ICU stay) and non-hospitalized (N=43) participants. Severity markers (IL6, D-dimer, procalcitonin, ferritin, ICAM-1, IL5, lipocalin, RAGE, TNFR, VEGFA, IFNγ, IL1β) were measured in plasma (mg/dL) using the Ella immunoassay and natural log transformed. Univariate negative binomial regression was performed to determine relative risk of hospitalization. Using the full marker panel, we performed a Principal Component Analysis (PCA) to determine directions of maximal variance in the data. Pearson's correlation coefficient was determined between analytes and each axis. RESULTS: Participants requiring ambulatory-, hospital-, and ICU-level care had samples collected at 44.0 (IQR: 35.0–51.0), 40.0 (13.0–51.0), and 47.5 (21.0–54.0) days, respectively. Higher unadjusted levels of IL6, D-dimer, procalcitonin, or ferritin were each associated with hospitalization (Table 1). The PCA showed a separation along axes between level of care and duration of symptoms (Fig 1). While significant correlations were noted with a number of biomarkers, PC1 most correlated with TNFR1 (r=0.88) and PC2 most correlated with IL6Ra (r=0.95). PC1 axis variation accounted for 36.5% of variance and the PC2 axis accounted for 20.0% of variance. Figure 1. Principal Component Analysis (PCA) of biomarkers by level ...

Following the 2013–2016 Ebola virus outbreak in West Africa, numerous groups advocated for the importance of executing clinical trials in outbreak settings. The difficulties associated with obtaining reliable data to support regulatory approval of investigational vaccines and therapeutics during that outbreak were a disappointment on a research and product development level, as well as on a humanitarian level. In response to lessons learned from the outbreak, the United States Department of Defense established a multi-institute project called the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC). JMEDICC's primary objective is to establish the technical capability in western Uganda to execute clinical trials during outbreaks of high-consequence pathogens such as the Ebola virus. A critical component of clinical trial execution is the establishment of laboratory operations. Technical, logistical, and political challenges complicate laboratory operations, and these challenges have been mitigated by JMEDICC to enable readiness for laboratory outbreak response operations.