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This work provides a method of estimating airway resistance along the bronchial tree in mechanically ventilated patients from time dependent lung volume data from the ventilator. A multi-compartment lung model is developed based on an analogy between electric circuits and the human lungs. A constrained linear least squares optimization method is formulated to solve the inverse problem of estimating the vector of airway resistance values in the alveolar tree with lung volume, compliance, and applied pressure as inputs. The outputs of the model are compared to data from the mechanical ventilator from 32 hospitalized ARDS patients, 12 of which had COVID-19. The solution of the inverse problem resulted in airway resistance vectors consistent with those in the literature, and time dependent lung volume estimates in good agreement with the the ventilator data. No statistically significant difference was found in the resistance vectors from patients with and without COVID-19. However, maximum and minimum pressures and compliance values were found to be of statistically significant difference. The method presented here holds promise for determining the airway resistance along the tree, and could be further developed with the aid of imaging. [ABSTRACT FROM AUTHOR]

Introduction: Post-acute sequelae of COVID-19 affects the quality of life of many COVID-19 survivors, yet the etiology of post-acute sequelae of COVID-19 remains unknown. We aimed to determine if persistent inflammation and ongoing T-cell activation during convalescence were a contributing factor to the pathogenesis of post-acute sequelae of COVID-19. Methods: We evaluated 67 individuals diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction for persistent symptoms during convalescence at separate time points occurring up to 180 days post-diagnosis. Fifty-two of these individuals were evaluated longitudinally. We obtained whole blood samples at each study visit, isolated peripheral blood mononuclear cells, and stained for multiple T cell activation markers for flow cytometry analysis. The activation states of participants' CD4+ and CD8+ T-cells were next analyzed for each of the persistent symptoms. Results: Overall, we found that participants with persistent symptoms had significantly higher levels of inflammation at multiple time points during convalescence when compared to those who fully recovered from COVID-19. Participants with persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of proliferating effector T-cells (CD8+Ki67+), and those with chest pain, joint pain, difficulty concentrating, and forgetfulness had higher levels of regulatory T-cells (CD4+CD25+). Additionally, those with dyspnea had significantly higher levels of CD8+CD38+, CD8+ Granzyme B+, and CD8+IL10+ cells. A retrospective comparison of acute phase inflammatory markers in adults with and without post-acute sequelae of COVID-19 showed that CD8+Ki67+ cells were significantly higher at the time of acute illness (up to 14 days post-diagnosis) in those who developed persistent dyspnea. Discussion: These findings suggest continued CD8+ T-cell activation following SARS-CoV-2 infection in adults experiencing post-acute sequelae of COVID-19 and that the increase in T regulatory cells for a subset of these patients represents the ongoing attempt by the host to reduce inflammation. [ABSTRACT FROM AUTHOR]

Introduction: Post-acute sequelae of COVID-19 affects the quality of life of many COVID-19 survivors, yet the etiology of post-acute sequelae of COVID-19 remains unknown. We aimed to determine if persistent inflammation and ongoing T-cell activation during convalescence were a contributing factor to the pathogenesis of post-acute sequelae of COVID-19., Methods: We evaluated 67 individuals diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction for persistent symptoms during convalescence at separate time points occurring up to 180 days post-diagnosis. Fifty-two of these individuals were evaluated longitudinally. We obtained whole blood samples at each study visit, isolated peripheral blood mononuclear cells, and stained for multiple T cell activation markers for flow cytometry analysis. The activation states of participants' CD4 + and CD8 + T-cells were next analyzed for each of the persistent symptoms., Results: Overall, we found that participants with persistent symptoms had significantly higher levels of inflammation at multiple time points during convalescence when compared to those who fully recovered from COVID-19. Participants with persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of proliferating effector T-cells (CD8 + Ki67 + ), and those with chest pain, joint pain, difficulty concentrating, and forgetfulness had higher levels of regulatory T-cells (CD4 + CD25 + ). Additionally, those with dyspnea had significantly higher levels of CD8 + CD38 + , CD8 + Granzyme B + , and CD8 + IL10 + cells. A retrospective comparison of acute phase inflammatory markers in adults with and without post-acute sequelae of COVID-19 showed that CD8 + Ki67 + cells were significantly higher at the time of acute illness (up to 14 days post-diagnosis) in those who developed persistent dyspnea., Discussion: These findings suggest continued CD8+ T-cell activation following SARS-CoV-2 infection in adults experiencing post-acute sequelae of COVID-19 and that the increase in T regulatory cells for a subset of these patients represents the ongoing attempt by the host to reduce inflammation., Competing Interests: BS is employed by Arcturus Therapeutics which is developing a COVID-19 vaccine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 LaVergne, Dutt, McFann, Baxter, Webb, Berry, Tipton, Stromberg, Sullivan, Dunn, Henao-Tamayo and Ryan.)

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3 + , CD4 + , and CD8 + ) in patients with severe disease and a significant increase in the CD56 + CD14 + Ki67 + IFN-γ + monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45 - CD31 + CD34 + CD146 + ), circulating endothelial progenitors (CD45 - CD31 + CD34 +/- CD146 - ), and neutrophils (CD11b + CD66b + ) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56 + monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination., (Copyright © 2022 by The American Association of Immunologists, Inc.)