RESUMEN
ObjectiveThe Seraph(R)100 Microbind Affinity Blood Filter(R) (Seraph 100) is an extracorporeal medical countermeasure that can remove many pathogens from blood, including the SARS-CoV-2 virus. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for severe coronavirus disease 2019 (COVID-19). DesignMulticenter retrospective observational cohort study. SettingIntensive care units across four of thirteen participating sites who have completed data extraction. PatientsCritically ill COVID-19 patients treated with Seraph 100 under an Emergency Use Authorization (n=53) and historical control patients who met criteria for treatment (n=46). InterventionExtracorporeal treatment with the Seraph 100 filter. Measurements and Main ResultsAt baseline, the median age was 61 years, 72.7% were male, and 59.6% required mechanical ventilation. The groups were matched in terms of sex, race/ethnicity, body mass index, APACHE II score, need for mechanical ventilation, and other COVID-19 treatments. However, patients in the Seraph 100 group were younger with a median age of 61 years (IQR 42-65) compared to controls who had a median age of 64 (IQR 56-68, p=0.036). The Seraph 100 group also had a lower median Charlson comorbidity index (2, IQR 0-3) compared to control patients (3, IQR 2-4, p=0.006). Mortality was lower in the Seraph 100 treated group compared to the historical controls (37.7% vs 67.4%, respectively, p=0.003). Multivariable logistic regression analysis yielded an odds ratio of 0.27 (95% confidence interval 0.09-0.79, p=0.016). Of the 53 patients treated with Seraph 100, only 1 patient experienced a serious adverse event (transient hypotension at the start of the treatment which required a brief period of vasopressor support). ConclusionsThese data suggest that broad spectrum, pathogen agnostic, extracorporeal blood purification technologies can be safely and effectively deployed to meet new pathogen threats as an adjunct to standard treatments while awaiting the development of directed pharmacologic therapies and/or vaccines.
RESUMEN
We report the first Human Immune System (HIS)-humanized mouse model ("DRAGA": HLA-A2.HLA-DR4.Rag1KO.IL-2R{gamma}cKO.NOD) for COVID-19 research. This mouse is reconstituted with human cord blood-derived, HLA-matched hematopoietic stem cells. It engrafts human epi/endothelial cells expressing the human ACE2 receptor for SARS-CoV-2 and TMPRSS2 serine protease co-localized on lung epithelia. HIS-DRAGA mice sustained SARS-CoV-2 infection, showing deteriorated clinical condition, replicating virus in the lungs, and human-like lung immunopathology including T-cell infiltrates, microthrombi and pulmonary sequelae. Among T-cell infiltrates, lung-resident (CD103+) CD8+ T cells were sequestered in epithelial (CD326+) lung niches and secreted granzyme B and perforin, indicating cytotoxic potential. Infected mice also developed antibodies against the SARS-CoV-2 viral proteins. Hence, HIS-DRAGA mice showed unique advantages as a surrogate in vivo human model for studying SARS-CoV-2 immunopathology and for testing the safety and efficacy of candidate vaccines and therapeutics.