scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Whole Blood ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Target Prediction ◽  
Data Driven ◽  
Host Responses ◽  
Drug Candidates ◽  
Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2020 ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Nikolaos Antonakos ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Whole Blood ◽  
Distress Syndrome ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Molecular Phenotype ◽  
Drug Candidates ◽  
Clinical Presentations ◽  
Patient Groups ◽  
Severe Patient

SUMMARYThe SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

scholarly journals Chronic microbial infections: Manipulation of host immunity as interventional approach

1970 ◽  
Vol 1 (1) ◽  
pp. 13-19
Author(s):  
Sheikh Mohammad Fazle Akbar ◽  
Md Sakirul Islam Khan ◽  
Shunji Mishiro
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Acute Infection ◽  
Immune Surveillance ◽  
Host Immune System ◽  
Related Factors ◽  
Chronic Viral Infections ◽  
Microbial Infections

Chronic viral infections represent major challenges in contemporary medicine, virology and pharmacology. The virus-bearing hosts are commonly found in every parts of the world and it is extremely difficult to manage these patients. In addition, considerable numbers of these patients develop progressive diseases and severe complications. Finally, most of these patients act as permanent reservoirs of virus. Understandings of viral life cycle during the last decade of 20th century and the first decade of 21st century have allowed development of hundreds of antiviral agents for different diseases. But, the clinical efficacy of these drugs is not yet satisfactory. In addition, virologists have provided conclusive evidences suggesting that eradication of most chronic virus from infected hosts may an unachievable goal. In this context, it is essential to develop alternative, novel, and evidence-based therapeutic maneuver for these patients. Manipulation of host immune system may be one of these approaches. We would discuss about scopes, limitations, and strategies for manipulation for controlling of chronic viral infections. The primary function of the host's immune system is to mount responses that protect the individual from various microbial infections including viruses. Host's immune responses also control the spread and virulence of the viruses [1]. This is applicable to viruses that cause acute infection. After entering the hosts, these viruses are localized in host's tissues, proliferate and induce antiviral immunity. These cellular events may cause damage and destruction of tissues and the host exhibit features of acute inflammatory diseases. However, the viruses are either almost completely eliminated from the hosts or adequately controlled in situ by host's immune systems. However, chronic infection is established by many viruses because the hosts induce improper and uncoordinated immune responses against these viruses. Most viruses cause persistent infection by evading the host immune surveillance mechanism. Both virus-related factors and host-dependent factors are primarily responsible for viral persistency in subjects with chronic viral infections.    doi: 10.3329/blj.v1i1.2620 Bangladesh Liver Journal Vol.1(1) 2009 p.13-19 

scholarly journals Immunomodulatory Role of Nutrients: How Can Pulmonary Dysfunctions Improve?

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Cristina Gozzi-Silva ◽  
Franciane Mouradian Emidio Teixeira ◽  
Alberto José da Silva Duarte ◽  
Maria Notomi Sato ◽  
Luana de Mendonça Oliveira
Keyword(s):  
Fatty Acids ◽  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Dietary Factors ◽  
Chronic Inflammatory Diseases ◽  
Anti Inflammatory ◽  
Lung Health

Nutrition is an important tool that can be used to modulate the immune response during infectious diseases. In addition, through diet, important substrates are acquired for the biosynthesis of regulatory molecules in the immune response, influencing the progression and treatment of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). In this way, nutrition can promote lung health status. A range of nutrients, such as vitamins (A, C, D, and E), minerals (zinc, selenium, iron, and magnesium), flavonoids and fatty acids, play important roles in reducing the risk of pulmonary chronic diseases and viral infections. Through their antioxidant and anti-inflammatory effects, nutrients are associated with better lung function and a lower risk of complications since they can decrease the harmful effects from the immune system during the inflammatory response. In addition, bioactive compounds can even contribute to epigenetic changes, including histone deacetylase (HDAC) modifications that inhibit the transcription of proinflammatory cytokines, which can contribute to the maintenance of homeostasis in the context of infections and chronic inflammatory diseases. These nutrients also play an important role in activating immune responses against pathogens, which can help the immune system during infections. Here, we provide an updated overview of the roles played by dietary factors and how they can affect respiratory health. Therefore, we will show the anti-inflammatory role of flavonoids, fatty acids, vitamins and microbiota, important for the control of chronic inflammatory diseases and allergies, in addition to the antiviral role of vitamins, flavonoids, and minerals during pulmonary viral infections, addressing the mechanisms involved in each function. These mechanisms are interesting in the discussion of perspectives associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its pulmonary complications since patients with severe disease have vitamins deficiency, especially vitamin D. In addition, researches with the use of flavonoids have been shown to decrease viral replication in vitro. This way, a full understanding of dietary influences can improve the lung health of patients.

scholarly journals COVID-19 and Crosstalk With the Hallmarks of Aging

2020 ◽  
Vol 75 (9) ◽  
pp. e34-e41 ◽  
Author(s):  
Shabnam Salimi ◽  
John M Hamlyn
Keyword(s):  
Older Adults ◽  
Immune System ◽  
Viral Infections ◽  
Kidney Injury ◽  
Severe Pneumonia ◽  
Biological Aging ◽  
Telomere Attrition ◽  
Drug Candidates ◽  
Severity Of The Disease ◽  
Health Complications

Abstract Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.

scholarly journals COVID-19 and Crosstalk With the Hallmarks of Aging

2020 ◽  
Author(s):  
Shabnam Salimi ◽  
John M. Hamlyn
Keyword(s):  
Older Adults ◽  
Immune System ◽  
Viral Infections ◽  
Kidney Injury ◽  
Severe Pneumonia ◽  
Biological Aging ◽  
Telomere Attrition ◽  
Drug Candidates ◽  
Severity Of The Disease ◽  
Health Complications

Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.

scholarly journals Neue Krankheiten mit Bluttranskriptomik entschlüsseln

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 372-375
Author(s):  
Thomas Ulas ◽  
Anna C. Aschenbrenner
Keyword(s):  
Immune Response ◽  
Data Driven ◽  
Host Responses ◽  
Specific Drug ◽  
Molecular Phenotype ◽  
Systemic Immune Response ◽  
Patient Subgroup ◽  
Drug Candidates ◽  
The World

AbstractThe COVID-19 pandemic is leading to increasing numbers of patients all over the world. Reports on a dysregulated immune system in the severe cases calls for a better characterization of the ongoing changes. To dissect COVID-19-driven immune host responses, we profiled whole blood transcriptomes enabling a data-driven stratification based on molecular phenotype. This analysis allowed prediction of patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

Infection, Immunodeficiency, and Inflammatory Diseases in Autoimmune Neurology

2018 ◽  
Vol 38 (03) ◽  
pp. 379-391 ◽  
Author(s):  
Stacey Clardy ◽  
Amanda Piquet
Keyword(s):  
Differential Diagnosis ◽  
Immune System ◽  
Physical Examination ◽  
Neurological Disease ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Critical Aspect ◽  
Immune Mediated ◽  
Comprehensive History

AbstractWhen patients present with neurological syndromes, such as encephalopathy/encephalitis, meningitis, and/or myelopathy/myelitis, the differential diagnosis is often broad, including infectious, inflammatory, autoimmune, vascular, and neoplastic etiologies. Just with inflammatory and autoimmune etiologies alone, there are numerous causative diseases. A comprehensive history and physical examination investigating for extraneurologic manifestations of immune-mediated disease is often necessary. Moreover, evaluating for an underlying infection and/or immunodeficiency becomes a critical aspect to the workup. This article will focus on the association of viral infections and dysregulation of the immune system as triggers of autoimmunity, in addition to various systemic inflammatory diseases that can cause neurological disease either with or without an established rheumatological disorder.

Rapid COVID-19 Prognostic Blood Test for Disease Severity Using Epigenetic Immune System Biomarkers

2020 ◽  
Vol 6 (2) ◽  
pp. 26-29
Author(s):  
Adam G. Marsh ◽  
G. Mark Anderson ◽  
Erich J. Izdepski
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Blood Test

Role of Rasayana in Prevention of COVID-19 - A Review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 716-722
Author(s):  
Sneha Dhakite ◽  
Sadhana Misar Wajpeyi
Keyword(s):  
Immune System ◽  
Respiratory System ◽  
Viral Infections ◽  
Cost Effective ◽  
The Body ◽  
Healthy Life ◽  
Vital Functions ◽  
Healthy Life Style ◽  
And Control

The “Coronavirus disease 19 (COVID-19)” is caused by “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, a newly discovered member of the Coronaviridae family of viruses which is a highly communicable. There is no effective medical treatment till date for Coronavirus disease hence prevention is the best way to keep disease away. Rasayana proved to be highly efficacious and cost effective for the Prevention and Control of viral infections when vaccines and standard therapies are lacking. Rasayana Chikitsa is one of the eight branches of Ashtanga Ayurveda which helps to maintain healthy life style. Rasayana improves immunity and performs many vital functions of human body. Vyadhikshamatva that is immune mechanism of the body is involved in Prevention of the occurrence of a new disease and it also decreases the virulence and progression of an existing disease. In COVID-19 the Respiratory system mainly get affected which is evident from its symptoms like cold, cough and breathlessness. Here the drugs help in enhancing immune system and strengthening functions of Respiratory system can be useful. For this purpose, the Rasayana like Chyavanprasha, Agastya Haritaki, Pippali Rasayana, Guduchi, Yashtimadhu, Haridra, Ashwagandha, Tulsi are used. Rasayana working on Respiratory system are best for Prevention of Coronavirus and boosting immune system. Rasayana Chikitsa can be effective in the Prevention as well as reducing symptoms of COVID-19.

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