COVID-19 Immunobiology: Lessons Learned, New Questions Arise

There is strong evidence that COVID-19 pathophysiology is mainly driven by a spatiotemporal immune deregulation. Both its phenotypic heterogeneity, spanning from asymptomatic to severe disease/death, and its associated mortality, are dictated by and linked to maladaptive innate and adaptive immune responses against SARS-CoV-2, the etiologic factor of the disease. Deregulated interferon and cytokine responses, with the contribution of immune and cellular stress-response mediators (like cellular senescence or uncontrolled inflammatory cell death), result in innate and adaptive immune system malfunction, endothelial activation and inflammation (endothelitis), as well as immunothrombosis (with enhanced platelet activation, NET production/release and complement hyper-activation). All these factors play key roles in the development of severe COVID-19. Interestingly, another consequence of this immune deregulation, is the production of autoantibodies and the subsequent development of autoimmune phenomena observed in some COVID-19 patients with severe disease. These new aspects of the disease that are now emerging (like autoimmunity and cellular senescence), could offer us new opportunities in the field of disease prevention and treatment. Simultaneously, lessons already learned from the immunobiology of COVID-19 could offer new insights, not only for this disease, but also for a variety of chronic inflammatory responses observed in autoimmune and (auto)inflammatory diseases.

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Pathophysiological and Clinical Aspects of Chronic Rhinosinusitis: Current Concepts

Frontiers in Allergy ◽

10.3389/falgy.2021.741788 ◽

2021 ◽

Vol 2 ◽

Author(s):

Stephan Vlaminck ◽

Frederic Acke ◽

Glenis K. Scadding ◽

Bart N. Lambrecht ◽

Philippe Gevaert

Keyword(s):

Chronic Rhinosinusitis ◽

Inflammatory Responses ◽

Adaptive Immune System ◽

Current Approach ◽

Clinical Aspects ◽

Adaptive Immune ◽

Clinical Observations ◽

Localized Disease ◽

Primary Focus

Adult chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses. According to the latest EPOS guidelines CRS should be regarded as primary or secondary with distinction between diffuse and localized disease. Further pathophysiologic research identified different inflammatory patterns leading to the term “endotyping of CRS.” The primary focus of endotyping is to define a dominant inflammatory type allowing for better orientation of therapy. The current approach proposes the differentiation between type 2 (eosinophilic) and non-type 2 inflammatory responses. In this review pathophysiological concepts of CRS will be discussed, focusing on the different inflammatory endotypes of T cells with special attention to the eosinophilic type 2 inflammatory response. The contribution of innate and adaptive immune system responses is presented. The possibility of endotyping based on sinonasal secretions sampling is brought to attention because it is indicative of corticosteroid responsiveness and available to most ENT surgeons. Furthermore, the clinical aspects of the three distinct phenotypes are analyzed in view of their characteristics, the related endoscopic findings, typical radiological imaging, histopathology findings, their relation toward allergy and obvious therapeutical implications. This overview will enable clinicians to relate pathophysiological patterns with clinical observations by explaining the different inflammatory mechanisms, hence providing a better understanding of therapy.

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Higher Circulating Concentration of Interleukin-38 in Patients with Knee Osteoarthritis: Its Association with Disease Severity

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v20i1.5418 ◽

2021 ◽

Author(s):

Mitra Abassifard ◽

Hossein Khorramdelazad ◽

Shayan Rezaee ◽

Abdollah Jafarzadeh

Keyword(s):

Inflammatory Responses ◽

Severe Disease ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Adaptive Immune ◽

Valuable Marker ◽

Vas Scores ◽

Blood Specimens ◽

Group Serum

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel antiinflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23 newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores>5 were higher than those with WOMAC scores<40, and VAS scores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner. The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

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The molecular basis of immune-based platelet disorders

Clinical Science ◽

10.1042/cs20191101 ◽

2020 ◽

Vol 134 (21) ◽

pp. 2807-2822

Author(s):

Sarah M. Hicks ◽

Christine S.M. Lee ◽

Sidra A. Ali ◽

Philip Y. Choi ◽

Elizabeth E. Gardiner

Keyword(s):

Inflammatory Responses ◽

Adaptive Immune System ◽

Significant Loss ◽

Innate Immune ◽

Predominant Role ◽

Platelet Surface ◽

Adaptive Immune ◽

Molecular Events ◽

Immunological Factors ◽

Platelet Disorders

Abstract Platelets have a predominant role in haemostasis, the maintenance of blood volume and emerging roles as innate immune cells, in wound healing and in inflammatory responses. Platelets express receptors that are important for platelet adhesion, aggregation, participation in inflammatory responses, and for triggering degranulation and enhancing thrombin generation. They carry a cargo of granules bearing enzymes, adhesion molecules, growth factors and cytokines, and have the ability to generate reactive oxygen species. The platelet is at the frontline of a host of cellular responses to invading pathogens, injury, and infection. Perhaps because of this intrinsic responsibility of a platelet to rapidly respond to thrombotic, pathological and immunological factors as part of their infantry role; platelets are susceptible to targeted attack by the adaptive immune system. Such attacks are often transitory but result in aberrant platelet activation as well as significant loss of platelet numbers and platelet function, paradoxically leading to elevated risks of both thrombosis and bleeding. Here, we discuss the main molecular events underlying immune-based platelet disorders with specific focus on events occurring at the platelet surface leading to activation and clearance.

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PPARγAgonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

PPAR Research ◽

10.1155/2013/519724 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Laurindo Ferreira da Rocha Junior ◽

Andréa Tavares Dantas ◽

Ângela Luzia Branco Pinto Duarte ◽

Moacyr Jesus Barreto de Melo Rego ◽

Ivan da Rocha Pitta ◽

...

Keyword(s):

Adaptive Immunity ◽

Inflammatory Diseases ◽

Cell Lineage ◽

Adaptive Immune System ◽

Innate And Adaptive Immunity ◽

Adaptive Immune ◽

Cytokines And Chemokines ◽

Autoimmune And Inflammatory Diseases ◽

Ppar Agonists ◽

T Cell Survival

Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγare members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγis activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγhas also been associated with B cells. The present review addresses these issues by placing PPARγagonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

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Machine learning identifies the immunological signature of Juvenile Idiopathic Arthritis

10.1101/382499 ◽

2018 ◽

Author(s):

Erika Van Nieuwenhove ◽

Vasiliki Lagou ◽

Lien Van Eyck ◽

James Dooley ◽

Ulrich Bodenhofer ◽

...

Keyword(s):

Machine Learning ◽

Juvenile Idiopathic Arthritis ◽

Large Scale ◽

Inflammatory Diseases ◽

Adaptive Immune System ◽

Healthy Children ◽

Adaptive Immune ◽

Systemic Jia ◽

Response Group ◽

Learning Analysis

AbstractJuvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, with a strongly debated pathophysiological origin. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. Here we profiled the adaptive immune system of 85 JIA patients and 43 age-matched controls, identifying immunological changes unique to JIA and others common across a broad spectrum of childhood inflammatory diseases. The JIA immune signature was shared between clinically distinct subsets, but was accentuated in the systemic JIA patients and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and JIA patients, machine learning analysis of the dataset proved capable of diagnosis of JIA patients with ~90% accuracy. These results pave the way for large-scale longitudinal studies of JIA, where machine learning could be used to predict immune signatures that correspond to treatment response group.

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Toll-Like Receptors: General Molecular and Structural Biology

Journal of Immunology Research ◽

10.1155/2021/9914854 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Payam Behzadi ◽

Herney Andrés García-Perdomo ◽

Tomasz M. Karpiński

Keyword(s):

Immune System ◽

Drug Discovery ◽

Structural Biology ◽

English Language ◽

Inflammatory Diseases ◽

Adaptive Immune System ◽

Toll Like Receptors ◽

Adaptive Immune ◽

Molecular Patterns

Background/Aim. Toll-like receptors (TLRs) are pivotal biomolecules in the immune system. Today, we are all aware of the importance of TLRs in bridging innate and adaptive immune system to each other. The TLRs are activated through binding to damage/danger-associated molecular patterns (DAMPs), microbial/microbe-associated molecular patterns (MAMPs), pathogen-associated molecular patterns (PAMPs), and xenobiotic-associated molecular patterns (XAMPs). The immunogenetic molecules of TLRs have their own functions, structures, coreceptors, and ligands which make them unique. These properties of TLRs give us an opportunity to find out how we can employ this knowledge for ligand-drug discovery strategies to control TLRs functions and contribution, signaling pathways, and indirect activities. Hence, the authors of this paper have a deep observation on the molecular and structural biology of human TLRs (hTLRs). Methods and Materials. To prepare this paper and fulfill our goals, different search engines (e.g., GOOGLE SCHOLAR), Databases (e.g., MEDLINE), and websites (e.g., SCOPUS) were recruited to search and find effective papers and investigations. To reach this purpose, we tried with papers published in the English language with no limitation in time. The iCite bibliometrics was exploited to check the quality of the collected publications. Results. Each TLR molecule has its own molecular and structural biology, coreceptor(s), and abilities which make them unique or a complementary portion of the others. These immunogenetic molecules have remarkable roles and are much more important in different sections of immune and nonimmune systems rather than that we understand to date. Conclusion. TLRs are suitable targets for ligand-drug discovery strategies to establish new therapeutics in the fields of infectious and autoimmune diseases, cancers, and other inflammatory diseases and disorders.

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Functional Roles of Syk in Macrophage-Mediated Inflammatory Responses

Mediators of Inflammation ◽

10.1155/2014/270302 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 71

Author(s):

Young-Su Yi ◽

Young-Jin Son ◽

Chongsuk Ryou ◽

Gi-Ho Sung ◽

Jong-Hoon Kim ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Innate Immune ◽

Innate Immune Responses ◽

Adaptive Immune Responses ◽

Functional Roles ◽

Pathogen Invasion ◽

Adaptive Immune ◽

Biological Responses

Inflammation is a series of complex biological responses to protect the host from pathogen invasion. Chronic inflammation is considered a major cause of diseases, such as various types of inflammatory/autoimmune diseases and cancers. Spleen tyrosine kinase (Syk) was initially found to be highly expressed in hematopoietic cells and has been known to play crucial roles in adaptive immune responses. However, recent studies have reported that Syk is also involved in other biological functions, especially in innate immune responses. Although Syk has been extensively studied in adaptive immune responses, numerous studies have recently presented evidence that Syk has critical functions in macrophage-mediated inflammatory responses and is closely related to innate immune response. This review describes the characteristics of Syk-mediated signaling pathways, summarizes the recent findings supporting the crucial roles of Syk in macrophage-mediated inflammatory responses and diseases, and discusses Syk-targeted drug development for the therapy of inflammatory diseases.

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Severe Adaptive Immune Suppression May be Why Patients with Severe COVID-19 Cannot be Discharged From the ICU Even After Negative Viral Tests

10.21203/rs.3.rs-709952/v1 ◽

2021 ◽

Author(s):

Yue Zhou ◽

Xuelian Liao ◽

Xiangrong Song ◽

Min He ◽

Fei Xiao ◽

...

Keyword(s):

Critically Ill ◽

Immune Suppression ◽

Inflammatory Responses ◽

Expression Profiles ◽

Severe Disease ◽

Antifungal Drugs ◽

The Body ◽

Adaptive Immune ◽

Secondary Infections

Abstract Background: During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. In general, continuous negative viral tests are thought to indicate that the virus has been cleared from the body and that the patients can be considered "recovered". However, because these patients were still critically ill, they obviously had not truly recovered from the disease. We sought to investigate why these patients were still critically ill even though they exhibited negative viral tests by analyzing the gene expression profiles of their peripheral immune cells using transcriptome sequencing.Methods: Fourteen severe COVID-19 patients with at least 3 negative virus tests but were still in critical ill and could not be discharged from the ICU were enrolled. Blood samples from 14 patients and 5 healthy donors were collected. Total RNA was extracted from nucleated cells for RNA-Sequencing. FeatureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. Results: All enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. This adaptive immune suppression is unlikely due to classic immune checkpoint molecules such as PD-1 or long-term use of glucocorticoids but may be caused by an unknown mechanism that has not yet been discovered.Conclusions: Our findings strongly suggest that an initial recovery of these severe COVID-19 patients, as indicated by negative viral tests, may not indicate actual recovery. They still suffer from secondary infections for a long period of time because of severe adaptive immunosuppression and need to receive a variety of antibiotics, antifungal drugs, or combination therapies. Appropriate methods should be used to detect their adaptive immune function, and appropriate immunotherapy that can activate the adaptive immune response should be developed. Trial registration: Not applicable (this study does not involve intervention on human participants).

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Severe Adaptive Immune Suppression May Be Why Patients With Severe COVID-19 Cannot Be Discharged From the ICU Even After Negative Viral Tests

Frontiers in Immunology ◽

10.3389/fimmu.2021.755579 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yue Zhou ◽

Xuelian Liao ◽

Xiangrong Song ◽

Min He ◽

Fei Xiao ◽

...

Keyword(s):

Immune Suppression ◽

Inflammatory Responses ◽

Expression Profiles ◽

Severe Disease ◽

Gene Expression Profiles ◽

Severe Infection ◽

Underlying Mechanism ◽

Adaptive Immune ◽

Secondary Infections ◽

Peripheral Immune Cells

During the COVID-19 pandemic, a phenomenon emerged in which some patients with severe disease were critically ill and could not be discharged from the ICU even though they exhibited negative viral tests. To explore the underlying mechanism, we collected blood samples from these patients and analyzed the gene expression profiles of peripheral immune cells. We found that all enrolled patients, regardless of changes in genes related to different symptoms and inflammatory responses, showed universally and severely decreased expression of adaptive immunity-related genes, especially those related to T/B cell arms and HLA molecules, and that these patients exhibited long-term secondary infections. In addition, no significant change was found in the expression of classic immunosuppression molecules including PD-1, PD-L1, and CTLA-4, suggesting that the adaptive immune suppression may not be due to the change of these genes. According to the published literatures and our data, this adaptive immunosuppression is likely to be caused by the “dysregulated host response” to severe infection, similar to the immunosuppression that exists in other severely infected patients with sepsis.

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Panic makes you more susceptible to covid-19 (Preprint)

10.2196/preprints.22053 ◽

2020 ◽

Author(s):

Md Musharraf Hossain ◽

Colin R Dunstan

Keyword(s):

Immune System ◽

Severe Acute Respiratory Syndrome ◽

Innate Immune System ◽

Severe Disease ◽

Adaptive Immune System ◽

Innate Immune ◽

Cytokine Storm ◽

Adaptive Immune ◽

Storm Response ◽

Short Period

UNSTRUCTURED COVID-19 is the official name describing the coronavirus disease causing by the virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). Its higher infection rate has led to worldwide spread making it a more dangerous threat than other coronavirus related diseases. As this virus spreads and responses from governments become more constraining of normal activities, we are seeing levels of anxiety among people increase over a relatively short period of time. When we are stressed the immune system’s ability to defend us from infections is reduced. Stress can suppress the innate immune system that provides the initial defence against viral infection making us more susceptible to Covid-19. In contrast, stress can cause overactivity of the adaptive immune system making a cytokine storm response leading to severe disease and death more likely. Management of stress levels has become an important strategy to reduce the risks of COVID-19.

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