Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes DOI Open Access
Mohammad Aminul Islam, Ashlee N. Ford Versypt

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 7, 2022

Abstract Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating effects these factors. Recent evidence shows patient-specific alterations RAS homeostasis concentrations with premorbidity expression level angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting suggests decreases, increases, or no changes peptides after SARS-CoV-2 infection. In addition, detailed mechanisms connecting conditions before infection to infection-induced still unknown. Here, multiscale computational model was developed quantify systemic contribution Three submodels were connected—an agent-based for in-host response tissue, dynamics model, fibrosis investigate patient-group-specific alteration collagen deposition lung. results indicated cell death due inflammatory as major contributor reduction ACE ACE2. contrast, there ACE2 viral-bound internalization explained possible previously published studies. Simulated consistent reported peptide values SARS-CoV-2-negative SARS-CoV-2-positive patients. decreased all virtual patient groups aging both sexes. large variations magnitude observed between male female patients older middle-aged groups. also affected showed feedback signaling renin could restore ANGI concentration but failed downstream ANGI. age significantly altered led slight depending on sex. This may find further applications calibrations tissue models acute chronic diseases develop personalized treatments.

Language: Английский

Mathematical modeling of impacts of patient differences on renin-angiotensin system and applications to COVID-19 lung fibrosis outcomes DOI Creative Commons
Mohammad Aminul Islam, Ashlee N. Ford Versypt

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 186, P. 109631 - 109631

Published: Jan. 2, 2025

Language: Английский

Citations

0
Circulating Autoantibodies Against Vasoactive Biomarkers Related to Orthostatic Intolerance in Long COVID Patients Compared to No-Long-COVID Populations: A Case-Control Study DOI Creative Commons
Emilie Han, Katrin Zlabinger, Ena Hašimbegović

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 300 - 300

Published: Feb. 18, 2025

Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 patients from our prospective POSTCOV registry and three control groups, each consisting 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative antispike protein SARS-CoV-2; Vaccinated healthy no history vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A (ETAR), beta-2 adrenergic (Beta-2 AR), angiotensin II 1 1-7 (Ang1-7) concentrations were measured enzyme-linked immunosorbent assay controls. Orthostatic was defined inappropriate sinus tachycardia, postural hypotonia other dysautonomia symptoms, such dizziness or blurred vision (n 38 patients). Autoantibody compared with routine laboratory parameters quality life questionnaires (EQ-5D). The concentration ETAR significantly higher COVID, Asymptomatic groups to the group. trend plasma Beta-2 AR Ang1-7 patients, not related presence intolerance. autoantibody showed significant positive correlation EQ-5D item "Problems performing usual activities".

Language: Английский

Citations

0
Mathematical Modeling of Impacts of Patient Differences on Renin-Angiotensin System and Applications to COVID-19 Lung Fibrosis Outcomes DOI Open Access
Mohammad Aminul Islam, Ashlee N. Ford Versypt

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 7, 2022

Abstract Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating effects these factors. Recent evidence shows patient-specific alterations RAS homeostasis concentrations with premorbidity expression level angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting suggests decreases, increases, or no changes peptides after SARS-CoV-2 infection. In addition, detailed mechanisms connecting conditions before infection to infection-induced still unknown. Here, multiscale computational model was developed quantify systemic contribution Three submodels were connected—an agent-based for in-host response tissue, dynamics model, fibrosis investigate patient-group-specific alteration collagen deposition lung. results indicated cell death due inflammatory as major contributor reduction ACE ACE2. contrast, there ACE2 viral-bound internalization explained possible previously published studies. Simulated consistent reported peptide values SARS-CoV-2-negative SARS-CoV-2-positive patients. decreased all virtual patient groups aging both sexes. large variations magnitude observed between male female patients older middle-aged groups. also affected showed feedback signaling renin could restore ANGI concentration but failed downstream ANGI. age significantly altered led slight depending on sex. This may find further applications calibrations tissue models acute chronic diseases develop personalized treatments.

Language: Английский

Citations

2