Conectar
by Vijeeth Guggilla, Jennifer A. Pacheco, Alexandre M. Carvalho, Grant R. Whitmer, Anna E. Pawlowski, Jodi L. Johnson, Catherine A. Gao, Chad J. Achenbach, Theresa L. Walunas
BackgroundAdults with immunosuppression are more likely to develop severe COVID-19 than adults without immunosuppression. Less is known about differences in outcomes for adults with immunosuppression who are hospitalized with COVID-19.
MethodsA retrospective cohort study of adults hospitalized with COVID-19 at Northwestern Medicine hospitals between 03/01/2020 and 05/31/2022 was performed. Regression analyses were performed comparing in-hospital mortality, intensive care unit (ICU) admission, oxygenation requirements, and hospital/ICU length of stay among patients without immunosuppression (n = 9079) and patients with immunosuppression (n = 873).
ResultsPatients with immunosuppression had significantly higher mortality than patients without immunosuppression (OR: 1.33, 95% CI: 1.11–1.60). This effect was even stronger when controlling for age at admission, diabetes, obesity, SARS-CoV-2 variant era, and COVID-19 medication use (adjusted OR: 1.78, 95% CI: 1.46–2.16). ICU admission (adjusted OR: 1.64, 95% CI: 1.41–1.90) and invasive ventilation (adjusted OR: 1.68, 95% CI: 1.36–2.06) were also significantly higher in patients with immunosuppression. Hospitalization length (median: 7 days) and ICU length of stay (median: 2.5 days) were longer in patients with immunosuppression compared to patients without immunosuppression (median: 5 days, adjusted p Conclusions
Patients with immunosuppression had worse outcomes than patients without immunosuppression. Subgroup analyses showed that patients with solid organ transplant had the worst outcomes overall. Patients with HIV had similar outcomes as patients without immunosuppression unless CD4 cell count was low.
by Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson
Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via intracerebroventricular (ICV) injections and received 3, 30, or 200 μg rhGNS in 4 doses over 2 weeks or vehicle. Twenty-four hours after the final dose, HS in brain and CSF showed dose-dependent reductions, reaching carrier levels in the higher dose groups. Furthermore, the proteomic perturbations that we described were corrected by rhGNS treatment. Next, Gns KO or carrier adult mice were treated via ICV and received 3, 30 or 200 μg rhGNS or vehicle once every two weeks (Day 1, 15, 29, 43, 57, 71, 85) and were euthanized on day 91. Following treatment, total HS and MPS IIID-specific HS (GlcNAc6S) showed dose-dependent reductions in brain and CSF and markers of neuroinflammation were substantially reduced. ICV enzyme replacement therapy with rhGNS restores CNS pathology of adult MPS IIID mice even with treatment at 14-day intervals, demonstrating preclinical efficacy for MPS IIID.by Gabriel Dumitrescu, Jovan Antovic, Nida Soutari, Charlotte Gran, Aleksandra Antovic, Kais Al-Abani, Jonathan Grip, Olav Rooyackers, Apostolos Taxiarchis
Complement and extracellular vesicles (EVs) association with thrombogenic tendencies is acknowledged, but limited evidence exists for their link to COVID-19 venous thromboembolism. This study aims to examine the relationship between pulmonary embolism and the expression of complement and other proteins related to thrombogenesis in severe Covid-19 patients. We included prospectively 207 severe COVID-19 patients and retrospectively screened for pulmonary embolism (PE). This analysis comprises 20 confirmed PE cases and 20 matched patients without PE. Blood samples taken at the admission in the intensive care unit were analyzed for complement using ELISA. EVs derived from neutrophils, endothelium, or platelets, as well carrying complement or tissue factor were analyzed using flow cytometry. Complement levels were markedly elevated, with a notable increase in C3a and Terminal Complement Complex. The most prevalent EV population was identified as tissue factor (TF)-carrying EVs which peaked in patients with PE during ICU days 4–9. However, for both the complement and analyzed EV populations, no statistically significant differences were found between the patients who developed pulmonary embolism and those who did not. In conclusion, complement factors and EVs expressing tissue factor, along with EVs derived from endothelial cells and platelets, are elevated in severe COVID-19 patients, regardless of the presence of pulmonary embolism. However, the involvement of complement and procoagulant EVs in peripheral plasma in the development of pulmonary embolism is still unclear and requires further investigation.
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