scholarly journals Molecular and cellular biomarkers in COVID-19 prognosis: design and methods – a prospective cohort TARGET protocol. (Preprint)

2020 ◽  
Author(s):  
Patricia Kurizky ◽  
Otávio Toledo Nóbrega ◽  
Alexandre Anderson Sousa Munhoz Soares ◽  
Rodrigo Barbosa Aires ◽  
Cleandro Pires de Albuquerque ◽  
...  

BACKGROUND Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relations between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation and haemostasis, comparing mild and severe forms of COVID-19. OBJECTIVE : In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation and haemostasis, comparing mild and severe forms of COVID-19. METHODS To accomplish these aims, we will analyse demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile and neutrophil function (ROS and NET production, phagocytosis, migration, gene expression and proteomics). Two hundred RT-PCR confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. RESULTS No data collection. CONCLUSIONS We believe that this information will provide more knowledge for ensuing studies that will provide more robust and useful clinical information that may allow for better decisions at the frontlines of health assistance. CLINICALTRIAL RBR-62zdkk


10.2196/24211 ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. e24211
Author(s):  
Patricia Kurizky ◽  
Otávio T Nóbrega ◽  
Alexandre Anderson De Sousa Munhoz Soares ◽  
Rodrigo Barbosa Aires ◽  
Cleandro Pires De Albuquerque ◽  
...  

Background Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. Methods To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction–confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. Results The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. Conclusions This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). Trial Registration Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk International Registered Report Identifier (IRRID) DERR1-10.2196/24211



mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Peter Jorth ◽  
Marvin Whiteley

ABSTRACTNatural transformation by competent bacteria is a primary means of horizontal gene transfer; however, evidence that competence drives bacterial diversity and evolution has remained elusive. To test this theory, we used a retrospective comparative genomic approach to analyze the evolutionary history ofAggregatibacter actinomycetemcomitans, a bacterial species with both competent and noncompetent sister strains. Through comparative genomic analyses, we reveal that competence is evolutionarily linked to genomic diversity and speciation. Competence loss occurs frequently during evolution and is followed by the loss of clustered regularly interspaced short palindromic repeats (CRISPRs), bacterial adaptive immune systems that protect against parasitic DNA. Relative to noncompetent strains, competent bacteria have larger genomes containing multiple rearrangements. In contrast, noncompetent bacterial genomes are extremely stable but paradoxically susceptible to infective DNA elements, which contribute to noncompetent strain genetic diversity. Moreover, incomplete noncompetent strain CRISPR immune systems are enriched for self-targeting elements, which suggests that the CRISPRs have been co-opted for bacterial gene regulation, similar to eukaryotic microRNAs derived from the antiviral RNA interference pathway.IMPORTANCEThe human microbiome is rich with thousands of diverse bacterial species. One mechanism driving this diversity is horizontal gene transfer by natural transformation, whereby naturally competent bacteria take up environmental DNA and incorporate new genes into their genomes. Competence is theorized to accelerate evolution; however, attempts to test this theory have proved difficult. Through genetic analyses of the human periodontal pathogenAggregatibacter actinomycetemcomitans, we have discovered an evolutionary connection between competence systems promoting gene acquisition and CRISPRs (clustered regularly interspaced short palindromic repeats), adaptive immune systems that protect bacteria against genetic parasites. We show that competentA. actinomycetemcomitansstrains have numerous redundant CRISPR immune systems, while noncompetent bacteria have lost their CRISPR immune systems because of inactivating mutations. Together, the evolutionary data linking the evolution of competence and CRISPRs reveals unique mechanisms promoting genetic heterogeneity and the rise of new bacterial species, providing insight into complex mechanisms underlying bacterial diversity in the human body.



2018 ◽  
Vol 34 (12) ◽  
pp. 2007-2014 ◽  
Author(s):  
Rhys D R Evans ◽  
Marilina Antonelou ◽  
Scott Henderson ◽  
Stephen B Walsh ◽  
Alan D Salama

AbstractSalt intake as part of a western diet currently exceeds recommended limits, and the small amount found in the natural diet enjoyed by our Paleolithic ancestors. Excess salt is associated with the development of hypertension and cardiovascular disease, but other adverse effects of excess salt intake are beginning to be recognized, including the development of autoimmune and inflammatory disease. Over the last decade there has been an increasing body of evidence demonstrating that salt affects multiple components of both the innate and adaptive immune systems. In this review we outline the recent laboratory, animal and human data, highlighting the effect of salt on immunity, with a particular focus on the relevance to inflammatory kidney disease.



2019 ◽  
Author(s):  
Adair L. Borges ◽  
Bardo Castro ◽  
Sutharsan Govindarajan ◽  
Tina Solvik ◽  
Veronica Escalante ◽  
...  

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulatingPseudomonas aeruginosavirulence and biofilm establishment, as a regulator of the biogenesis and activity of the Type I-F CRISPR-Cas system. Downstream of the KinB/AlgB system, activators of biofilm production AlgU (a σEorthologue) and AlgR, act as repressors of CRISPR-Cas activity during planktonic and surface-associated growth. AmrZ, another biofilm activator, functions as a surface-specific repressor of CRISPR-Cas immunity.Pseudomonasphages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ, which are functional CRISPR-Cas repressors. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.



2021 ◽  
Author(s):  
Hélène Chabas ◽  
Viktor Müller ◽  
Sebastian Bonhoeffer ◽  
Roland R. Regoes

AbstractAdaptive immune systems face a control challenge: they should react with enough strength to clear an infection while avoiding to harm their organism. CRISPR-Cas systems are adaptive immune systems of prokaryotes that defend against fast evolving viruses. Here, we explore the CRISPR-Cas control challenge and look how its reactivity, i.e. its probability to acquire a new resistance, impacts the epidemiological outcome of a phage outbreak and the prokaryote’s fitness. We show that in the absence of phage evolution, phage extinction is driven by the probability to acquire at least one resistance. However, when phage evolution is fast, phage extinction is driven by an epidemiological critical threshold: any reactivity below this critical threshold leads to phage survival whereas any reactivity above it leads to phage extinction. We also show that in the absence of autoimmunity, high levels of reactivity evolve. However, when CRISPR-Cas systems are prone to autoimmune reactions, intermediate levels of reactivity are evolutionarily optimal. These results help explaining why natural CRISPR-Cas systems do not show high levels of reactivity.



Author(s):  
Yihan Li ◽  
Simon M. Laws ◽  
Luke A. Miles ◽  
James S. Wiley ◽  
Xin Huang ◽  
...  


2021 ◽  
Vol 71 (2) ◽  
pp. 61-64
Author(s):  
Indah Bachti Setyarini ◽  
Nurul Ratna ◽  
Ninik Mudjihartini

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, affecting millions of people worldwide due to its ease of transmission. Despite limited information on effective therapeutic options, vitamin D has been regularly reported to exert beneficial immunomodulatory effects affecting both innate and adaptive immune systems. As it is synthesized in the skin under ultraviolet radiation, population living in equatorial countries are presumed to have adequate vitamin D, however several studies have shown otherwise. This article is aimed to give an insight on the different mechanisms by which vitamin D affects our immune system in COVID-19, as well as discussing correlation of having sunlight all year round by being near the equator towards vitamin D adequacy.



2019 ◽  
pp. 2-20
Author(s):  
Bibiana Bielekova

The chapter begins with a short introduction to the components of the immune system, outlining both the innate and adaptive components. It discusses the role of the immune system in protecting against infections and abnormal tissues. It describes the concepts of self-antigens, antigen presentation, and immune synapse. It then examines immune tolerance and the differing functions and capacities of the innate and adaptive immune systems. Finally, the chapter considers infections and autoimmune phenomena and how the immune system responds to these challenges.





2001 ◽  
Vol 44 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Kenneth J. Warrington ◽  
Seisuke Takemura ◽  
J�rg J. Goronzy ◽  
Cornelia M. Weyand


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