scholarly journals In silico dynamics of COVID-19 phenotypes for optimizing clinical management

2021 ◽  
Vol 118 (3) ◽  
pp. e2021642118
Author(s):  
Chrysovalantis Voutouri ◽  
Mohammad Reza Nikmaneshi ◽  
C. Corey Hardin ◽  
Ankit B. Patel ◽  
Ashish Verma ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Management ◽  
Thrombus Formation ◽  
Renin Angiotensin System ◽  
Coagulation Cascade ◽  
Mathematical Framework ◽  
Sustained Response Rate ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Insight Into

Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, incorporating the renin−angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines, and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of comorbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age; comorbidities such as obesity, diabetes, and hypertension; and dysregulated immune response. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment—or combination of treatments—depends on the preinfection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19.

scholarly journals In silico dynamics of COVID-19 phenotypes for optimizing clinical management

2020 ◽  
Author(s):  
Chrysovalantis Voutouri ◽  
Mohammad Reza Nikmaneshi ◽  
C. Corey Hardin ◽  
Ankit B. Patel ◽  
Ashish Verma ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Management ◽  
Thrombus Formation ◽  
Renin Angiotensin System ◽  
Coagulation Cascade ◽  
Mathematical Framework ◽  
Sustained Response Rate ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Insight Into

Abstract Understanding the underlying mechanisms of COVID-19 progression and the impact of various pharmaceutical interventions is crucial for the clinical management of the disease. We developed a comprehensive mathematical framework based on the known mechanisms of the SARS-CoV-2 virus infection, incorporating the renin-angiotensin system and ACE2, which the virus exploits for cellular entry, key elements of the innate and adaptive immune responses, the role of inflammatory cytokines and the coagulation cascade for thrombus formation. The model predicts the evolution of viral load, immune cells, cytokines, thrombosis, and oxygen saturation based on patient baseline condition and the presence of co-morbidities. Model predictions were validated with clinical data from healthy people and COVID-19 patients, and the results were used to gain insight into identified risk factors of disease progression including older age, co-morbidities such as obesity, diabetes, and hypertension, and dysregulated immune response 1,2. We then simulated treatment with various drug classes to identify optimal therapeutic protocols. We found that the outcome of any treatment depends on the sustained response rate of activated CD8+ T cells and sufficient control of the innate immune response. Furthermore, the best treatment –or combination of treatments – depends on the pre-infection health status of the patient. Our mathematical framework provides important insight into SARS-CoV-2 pathogenesis and could be used as the basis for personalized, optimal management of COVID-19.

scholarly journals The Impact of COVID-19 Pandemic on Management and Outcome in Patients with Heart Failure

2021 ◽  
Vol 10 (23) ◽  
pp. 5577
Author(s):  
Zahi Abu Ghosh ◽  
Donna R. Zwas ◽  
Andre Keren ◽  
Gabby Elbaz-Greener ◽  
Vered Israeli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mortality Rate ◽  
Clinical Management ◽  
Respiratory Infections ◽  
Renin Angiotensin System ◽  
Mortality Rates ◽  
High Morbidity ◽  
Patients With Heart Failure ◽  
The Impact ◽  
Diabetes And Obesity

Background: The COVID-19 pandemic has adversely affected the provision of health care and disease management around the world. COVID-19 carries a high morbidity and mortality rate in elderly and people with comorbidities, including heart failure (HF). The present study addressed the clinical management and outcomes of HF patients during the pandemic. Methods: We evaluated the clinical management and survival rate of HF patients during the COVID-19 pandemic in Israel (March 2020–April 2021). Results: The cohort included 6748 patients with a diagnosis of HF during the study period. During this period, 843 HF patients (12.5%) were infected with COVID-19, and 194 died from COVID-19, a 23% mortality rate. Patients infected with COVID-19 had a higher percentage of diabetes and obesity. Predictors of mortality included age, male sex, reduced functional capacity, renal dysfunction, and absence of renin–angiotensin system inhibition. During the pandemic, there was a marked decrease in the usage of medical services in the cohort. Cardiovascular hospitalizations, all hospitalization, and emergency room visits were significantly decreased compared to the two years prior to the pandemic, particularly during the lockdowns. There was also an initial decrease in HF clinic visits. Mortality rates were very similar during the pandemic compared to previous years. There was a decline in non-COVID-19 deaths, which were replaced with deaths due to COVID-19. This may result from competing effects and reduced exposure to respiratory infections and other insults due to social distancing. Conclusions: Mortality rates in HF patients infected with COVID-19 were high. The COVID-19 pandemic resulted in the reduced usage of health services but without increased overall mortality.

scholarly journals Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics

2022 ◽  
Vol 8 ◽  
Author(s):  
Yue Liu ◽  
Jiaqi Wang ◽  
Changxin Wu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Gut Microbiota ◽  
Bioactive Metabolites ◽  
Beneficial Effects ◽  
Complex Microbial Community ◽  
Host Health ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Wall Components

The human gastrointestinal tract harbours a complex microbial community, which interacts with the mucosal immune system closely. Gut microbiota plays a significant role in maintaining host health, which could supply various nutrients, regulate energy balance, modulate the immune response, and defence against pathogens. Therefore, maintaining a favourable equilibrium of gut microbiota through modulating bacteria composition, diversity, and their activity is beneficial to host health. Several studies have shown that probiotics and pre-biotics could directly and indirectly regulate microbiota and immune response. In addition, post-biotics, such as the bioactive metabolites, produced by gut microbiota, and/or cell-wall components released by probiotics, also have been shown to inhibit pathogen growth, maintain microbiota balance, and regulate an immune response. This review summarises the studies concerning the impact of probiotics, pre-biotics, and post-biotics on gut microbiota and immune systems and also describes the underlying mechanisms of beneficial effects of these substances. Finally, the future and challenges of probiotics, pre-biotics, and post-biotics are proposed.

Asymmetrical Attribution of Performance in China

Asian Survey ◽  
2020 ◽  
Vol 60 (5) ◽  
pp. 978-1003
Author(s):  
Jacqueline Chen Chen ◽  
Jun Xiang
Keyword(s):  
Economic Development ◽  
Local Governments ◽  
Central Government ◽  
Cultural Theory ◽  
Political Trust ◽  
Mediation Model ◽  
Multilevel Mediation ◽  
Dual Pathway ◽  
Underlying Mechanisms ◽  
The Impact

Existing studies of the impact of economic development on political trust in China have two major gaps: they fail to explain how economic development contributes to the hierarchical trust pattern, and they do not pay enough attention to the underlying mechanisms. In light of cultural theory and political control theory, we propose adapting performance theory into a theory of “asymmetrical attribution of performance” to better illuminate the case of China. This adapted theory leads to dual pathway theses: expectation fulfillment and local blaming. Using a multilevel mediation model, we show that expectation fulfillment mainly upholds trust in the central government, whereas local blaming undermines trust in local governments. We also uncover a rural–urban distinction in the dual pathway, revealing that both theses are more salient among rural Chinese.

The Renin-Angiotensin System: New Insight into Old Therapies

2013 ◽  
Vol 20 (10) ◽  
pp. 1313-1322 ◽  
Author(s):  
M. Ramirez-Sanchez ◽  
I. Prieto ◽  
R. Wangensteen ◽  
I. Banegas ◽  
A. B. Segarra ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Insight Into

Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension

2019 ◽  
Vol 17 (2) ◽  
pp. 180-190 ◽  
Author(s):  
V. Katsi ◽  
G. Georgiopoulos ◽  
D. Oikonomou ◽  
C. Aggeli ◽  
C. Grassos ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Stenosis ◽  
Aortic Regurgitation ◽  
Antihypertensive Agents ◽  
Renin Angiotensin System ◽  
Aortic Disease ◽  
Review Of The Literature ◽  
Angiotensin System ◽  
The Impact ◽  
Worse Prognosis

Background: Hypertension (HT) is an important risk factor for cardiovascular disease and might precipitate pathology of the aortic valve. </P><P> Objective: To investigate the association of HT with aortic dysfunction (including both aortic regurgitation and stenosis) and the impact of antihypertensive treatment on the natural course of underlying aortic disease. </P><P> Methods: We performed a systematic review of the literature for all relevant articles assessing the correlation between HT and phenotype of aortic disease. </P><P> Results: Co-existence of HT with aortic stenosis and aortic regurgitation is highly prevalent in hypertensive patients and predicts a worse prognosis. Certain antihypertensive agents may improve haemodynamic parameters (aortic jet velocity, aortic regurgitation volume) and remodeling of the left ventricle, but there is no strong evidence of benefit regarding clinical outcomes. Renin-angiotensin system inhibitors, among other vasodilators, are well-tolerated in aortic stenosis. </P><P> Conclusion: Several lines of evidence support a detrimental association between HT and aortic valve disease. Therefore, HT should be promptly treated in aortic valvulopathy. Despite conventional wisdom, specific vasodilators can be used with caution in aortic stenosis.

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

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