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BACKGROUND: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints. METHODS: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms. RESULTS: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms. CONCLUSIONS: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC.
RESUMO
The blood-brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing-models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non-biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L-lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi-porous membranes, these membranes significantly improve the expression of BBB-related proteins in brain endothelial cells. PEA-coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF-2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA-fibronectin membranes. This enables the generation of high-throughput drug permeability models without the need of complicated co-culture conditions.
RESUMO
Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.