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1. Loss of pulsatility with continuous‐flow left ventricular assist devices and the significance of the arterial endothelium in von‐Willebrand factor production and degradation

   https://doi.org/10.1111/aor.14456  

   Giridharan, Guruprasad A.; Berg, Ian C.; Ismail, Esraa; Nguyen, Khanh T.; Hecking, Jana; Kirklin, James K.; Cheng, Xuanhong; Sethu, Palaniappan (April 2023, Artificial Organs)

   Patients on continuous flow ventricular assist devices (CF-VADs) are at high risk for the development of Acquired von-Willebrand Syndrome (AVWS) and non-surgical bleeding. von Willebrand Factor (vWF) plays an essential role in maintaining hemostasis via platelet binding to the damaged endothelium to facilitate coagulation. In CF-VAD patients, degradation of vWF into low MW multimers that are inefficient in facilitating coagulation occurs and has been primarily attributed to the supraphysiological shear stress associated with the CF-VAD impeller. Methods In this review, we evaluate information from the literature regarding the unraveling behavior of surface-immobilized vWF under pulsatile and continuous flow pertaining to: (A) the process of arterial endothelial vWF production and release into circulation, (B) the critical shear stress required to unravel surface bound versus soluble vWF which leads to degradation, and (C) the role of pulsatility in on the production and degradation of vWF. Results and Conclusion Taken together, these data suggests that the loss of pulsatility and its impact on arterial endothelial cells plays an important role in the production, release, unraveling, and proteolytic degradation of vWF into low MW multimers, contributing to the development of AVWS. Restoration of pulsatility can potentially mitigate this issue by preventing AVWS and minimizing the risk of non-surgical bleeding. 

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2. Understanding Neutrophil Dynamics during COVID-19 Infection

   https://doi.org/10.3390/app13042409  

   Murphy, Quiyana M.; Ciupe, Stanca M. (February 2023, Applied Sciences)

   Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in varied clinical outcomes, with virus-induced chronic inflammation and tissue injury being associated with enhanced disease pathogenesis. To determine the role of tissue damage on immune populations recruitment and function, a mathematical model of innate immunity following SARS-CoV-2 infection has been proposed. The model was fitted to published longitudinal immune marker data from patients with mild and severe COVID-19 disease and key parameters were estimated for each clinical outcome. Analytical, bifurcation, and numerical investigations were conducted to determine the effect of parameters and initial conditions on long-term dynamics. The results were used to suggest changes needed to achieve immune resolution. 

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3. Gut bacterial lactate stimulates lung epithelial mitochondria and exacerbates acute lung injury

   https://doi.org/10.1101/2025.03.24.645052  

   Upadhyay, Vaibhav; Ortega, Edwin F; Ramirez_Hernandez, Luis A; Alexander, Margaret; Kaur, Gagandeep; Trepka, Kai; Rock, Rachel R; Shima, Rafaella T; Cheshire, W Colby; Alipanah-Lechner, Narges; et al (March 2025, bioRxiv)

   ABSTRACT Acute respiratory distress syndrome (ARDS) is an often fatal critical illness where lung epithelial injury leads to intrapulmonary fluid accumulation. ARDS became widespread during the COVID-19 pandemic, motivating a renewed effort to understand the complex etiology of this disease. Rigorous prior work has implicated lung endothelial and epithelial injury in response to an insult such as bacterial infection; however, the impact of microorganisms found in other organs on ARDS remains unclear. Here, we use a combination of gnotobiotic mice, cell culture experiments, and re-analyses of a large metabolomics dataset from ARDS patients to reveal that gut bacteria impact lung cellular respiration by releasing metabolites that alter mitochondrial activity in lung epithelium. Colonization of germ-free mice with a complex gut microbiota stimulated lung mitochondrial gene expression. A single human gut bacterial species,Bifidobacterium adolescentis,was sufficient to replicate this effect, leading to a significant increase in mitochondrial membrane potential in lung epithelial cells. We then used genome sequencing and mass spectrometry to confirm thatB. adolescentisproducesL-lactate, which was sufficient to increase mitochondrial activity in lung epithelial cells. Finally, we found that serum lactate was significantly associated with disease severity in patients with ARDS from the Early Assessment of Renal and Lung Injury (EARLI) cohort. Together, these results emphasize the importance of more broadly characterizing the microbial etiology of ARDS and other lung diseases given the ability of gut bacterial metabolites to remotely control lung cellular respiration. Our discovery of a single bacteria-metabolite pair provides aproof-of-conceptfor systematically testing other microbial metabolites and a mechanistic biomarker that could be pursued in future clinical studies. Furthermore, our work adds to the growing literature linking the microbiome to mitochondrial function, raising intriguing questions as to the bidirectional communication between our endo- and ecto-symbionts. 

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4. Metabolite, protein, and tissue dysfunction associated with COVID-19 disease severity

   https://doi.org/10.1038/s41598-022-16396-9  

   Rahnavard, Ali; Mann, Brendan; Giri, Abhigya; Chatterjee, Ranojoy; Crandall, Keith A. (July 2022, Scientific Reports)

   Abstract Proteins are direct products of the genome and metabolites are functional products of interactions between the host and other factors such as environment, disease state, clinical information, etc. Omics data, including proteins and metabolites, are useful in characterizing biological processes underlying COVID-19 along with patient data and clinical information, yet few methods are available to effectively analyze such diverse and unstructured data. Using an integrated approach that combines proteomics and metabolomics data, we investigated the changes in metabolites and proteins in relation to patient characteristics (e.g., age, gender, and health outcome) and clinical information (e.g., metabolic panel and complete blood count test results). We found significant enrichment of biological indicators of lung, liver, and gastrointestinal dysfunction associated with disease severity using publicly available metabolite and protein profiles. Our analyses specifically identified enriched proteins that play a critical role in responses to injury or infection within these anatomical sites, but may contribute to excessive systemic inflammation within the context of COVID-19. Furthermore, we have used this information in conjunction with machine learning algorithms to predict the health status of patients presenting symptoms of COVID-19. This work provides a roadmap for understanding the biochemical pathways and molecular mechanisms that drive disease severity, progression, and treatment of COVID-19. 

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5. Key Radiological Features of COVID-19 Chest CT Scans with a Focuson Special Subgroups: A Literature Review

   https://doi.org/10.2174/1573405618666220620125332  

   Nouaili, Noor; Garner, Rachael; Salehi, Sana; Rocca, Marianna La; Duncan, Dominique (April 2023, Current Medical Imaging Formerly Current Medical Imaging Reviews)

   Abstract: In 2019, a series of novel pneumonia cases later known as Coronavirus Disease 2019 (COVID-19) were reported in Wuhan, China. Chest computed tomography (CT) has played a key role in the management and prognostication in COVID-19 patients. CT has demonstrated 98%sensitivity in detecting COVID-19, including identifying lung abnormalities that are suggestive of COVID-19, even among asymptomatic individuals. Methods: We conducted a comprehensive literature review of 17 published studies, including focuses on three subgroups, pediatric patients, pregnant women, and patients over 60 years old, to identify key characteristics of chest CT in COVID-19 patients. Results: Our comprehensive review of the 17 studies concluded that the main CT imaging finding is ground glass opacities (GGOs) regardless of patient age. We also identified that crazy paving pattern, reverse halo sign, smooth or irregular septal thickening, and pleural thickening may serve as indicators of disease progression. Lesions on CT scans were dominantly distributed in the peripheral zone with multilobar involvement, specifically concentrated in the lower lobes. In the patients over 60 years old, the proportion of substantial lobe involvement was higher than the controlgroup and crazy paving signs, bronchodilation, and pleural thickening were more commonly present. Conclusion: Based on all 17 studies, CT findings in COVID-19 have shown a predictable pattern of evolution over the disease. These studies have proven that CT may be an effective approach for early screening and detection of COVID-19. 

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