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1.
PLoS One ; 16(12): e0261333, 2021.
Article in English | MEDLINE | ID: covidwho-1779728

ABSTRACT

Allergic airway disease is the most common chronic airway inflammatory disorder in developed countries. House dust mite, cockroach, and mold are the leading allergens in most tropical and subtropical countries, including Taiwan. As allergen avoidance is difficult for patients allergic to these perennial indoor allergens, allergen-specific immunotherapy (ASIT) is the only available allergen-specific and disease-modifying treatment. However, for patients sensitized to multiple allergens, ASIT using each corresponding allergen is cumbersome. In the present study, we developed a recombinant L. lactis vaccine against the three most common indoor aeroallergens and investigated its effectiveness for preventing respiratory allergy and safety in mice. Three recombinant clones of Der p 2 (mite), Per a 2 (roach), and Cla c 14 (mold) were constructed individually in pNZ8149 vector and then electroporated into host strain L.lactis NZ3900. BALB/c mice were fed with the triple vaccine 5 times per week for 4 weeks prior to sensitization. The effectiveness and safety profile were then determined. Oral administration of the triple vaccine significantly alleviated allergen-induced airway hyper-responsiveness in the vaccinated mice. The allergen-specific IgG2a was upregulated. IL-4 and IL-13 mRNA expressions as well as inflammatory cell infiltration in the lungs decreased significantly in the vaccinated groups. No body weight loss or abnormal findings in the liver and kidneys were found in any of the groups of mice. This is the first report to describe a triple-aeroallergen vaccine using a food-grade lactococcal expression system. We developed a convenient oral delivery system and intend to extend this research to develop a vaccination that can be self-administered at home by patients.


Subject(s)
Allergens/chemistry , Asthma/immunology , Desensitization, Immunologic/methods , Hypersensitivity/metabolism , Lactococcus lactis , Vaccines , Animals , Antigens, Dermatophagoides/chemistry , Antigens, Dermatophagoides/immunology , Arthropod Proteins/chemistry , Electroporation , Female , Fermentation , Insect Proteins , Mice , Mice, Inbred BALB C , Pyroglyphidae/immunology , Respiratory Hypersensitivity/prevention & control
2.
Front Immunol ; 12: 796094, 2021.
Article in English | MEDLINE | ID: covidwho-1690446

ABSTRACT

It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2/immunology , Asthma/immunology , COVID-19/immunology , Cytokines/immunology , Gene Expression Regulation/immunology , Lung/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Male , Middle Aged , Serine Endopeptidases/immunology
3.
J Immunol ; 208(6): 1467-1482, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1690085

ABSTRACT

Asthma is a chronic disease of childhood, but for unknown reasons, disease activity sometimes subsides as children mature. In this study, we present clinical and animal model evidence suggesting that the age dependency of childhood asthma stems from an evolving host response to respiratory viral infection. Using clinical data, we show that societal suppression of respiratory virus transmission during coronavirus disease 2019 lockdown disrupted the traditional age gradient in pediatric asthma exacerbations, connecting the phenomenon of asthma remission to virus exposure. In mice, we show that asthmatic lung pathology triggered by Sendai virus (SeV) or influenza A virus is highly age-sensitive: robust in juvenile mice (4-6 wk old) but attenuated in mature mice (>3 mo old). Interestingly, allergen induction of the same asthmatic traits was less dependent on chronological age than viruses. Age-specific responses to SeV included a juvenile bias toward type 2 airway inflammation that emerged early in infection, whereas mature mice exhibited a more restricted bronchiolar distribution of infection that produced a distinct type 2 low inflammatory cytokine profile. In the basal state, aging produced changes to lung leukocyte burden, including the number and transcriptional landscape of alveolar macrophages (AMs). Importantly, depleting AMs in mature mice restored post-SeV pathology to juvenile levels. Thus, aging influences chronic outcomes of respiratory viral infection through regulation of the AM compartment and type 2 inflammatory responses to viruses. Our data provide insight into how asthma remission might develop in children.


Subject(s)
Age Factors , Aging/physiology , Asthma/immunology , COVID-19/immunology , Influenza A virus/physiology , Influenza, Human/immunology , Lung/immunology , Orthomyxoviridae Infections/immunology , Respirovirus Infections/immunology , SARS-CoV-2/physiology , Sendai virus/physiology , Th2 Cells/immunology , Animals , Asthma/epidemiology , COVID-19/epidemiology , Cytokines/metabolism , Humans , Influenza, Human/epidemiology , Mice , Mice, Inbred C57BL , United States/epidemiology
4.
J Allergy Clin Immunol ; 149(2): 455-465, 2022 02.
Article in English | MEDLINE | ID: covidwho-1676782

ABSTRACT

Severe asthma is a heterogeneous disease encompassing different phenotypes and endotypes. Although patients with severe asthma constitute a small proportion of the total population with asthma, they largely account for the morbidity and mortality associated with asthma, indicating a clear unmet need. Being distinct from mild and moderate disease, new insights into the immunopathogenesis of severe asthma are needed. The disease endotypes have provided better insights into the immunopathogenic mechanisms underlying severe asthma. Current stratified approach of treating severe asthma based on phenotypes is met with shortcomings, necessitating unbiased multidimensional endotyping to cope with disease complexity. Therefore, in this review, we explore the distinct endotypes and their mechanistic pathways that characterize the heterogeneity observed in severe asthma.


Subject(s)
Asthma/immunology , Airway Remodeling , Asthma/etiology , Asthma/therapy , Autophagy/physiology , Bronchial Thermoplasty , Humans , Mitochondria/physiology , Obesity/complications , Th17 Cells/immunology , Th2 Cells/immunology
5.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1595807

ABSTRACT

The IL-4 and IL-13 cytokine pathways play integral roles in stimulating IgE inflammation, with the IL-4 cytokine being a major cytokine in the etiology of thunderstorm asthma, atopic dermatitis, and allergic rhinitis. The increasing prevalence of thunderstorm asthma in the younger population and the lessening efficacy of corticosteroids and other anti-inflammatories has created a need for more effective pharmaceuticals. This review summarizes the IL-4 and IL-13 pathways while highlighting and discussing the current pathway inhibitors aimed at treating thunderstorm asthma and atopic dermatitis, as well as the potential efficacy of peptide therapeutics in this field.


Subject(s)
Allergens/adverse effects , Asthma/immunology , Dermatitis, Atopic/immunology , Interleukin-4/metabolism , Allergens/immunology , Asthma/drug therapy , Dermatitis, Atopic/drug therapy , Gene Expression Regulation/drug effects , Humans , Interleukin-13/metabolism , Molecular Targeted Therapy , Signal Transduction/drug effects
7.
J Allergy Clin Immunol ; 149(2): 569-578, 2022 02.
Article in English | MEDLINE | ID: covidwho-1587444

ABSTRACT

Our understanding of risk factors and interventions influencing outcomes from coronavirus disease 2019 (COVID-19) has continued to evolve, revealing advances emerging from hypotheses formed at the start of the pandemic. Epidemiologic studies have shown that asthma control, rather than a diagnosis of asthma, is a determinant of COVID-19 severity. Clinical outcomes in patients with primary immunodeficiencies, even in those with impaired cellular immunity, are variable. IL-6 has emerged as a reliable biomarker of COVID-19 severity, and large clinical trials have shown the potential for improving outcomes through inhibition of IL-6 signaling in some patients. Studies of genetic risk factors for severe COVID-19 have also revealed the importance of interferon homeostasis in the defense against severe acute respiratory syndrome coronavirus 2. Because COVID-19 vaccines constitute the primary tool for ending this pandemic, strategies have been developed to address potential allergic and immune-mediated reactions. Here, we discuss advances in our understanding of COVID-19 risk factors and outcomes within the context of allergic and immunologic mechanisms.


Subject(s)
Antiviral Agents/therapeutic use , Asthma/therapy , Biological Products/therapeutic use , COVID-19/therapy , Immunologic Deficiency Syndromes/therapy , SARS-CoV-2/drug effects , Antibodies, Monoclonal/therapeutic use , Asthma/immunology , Asthma/mortality , Asthma/virology , Azetidines/therapeutic use , Biomarkers/metabolism , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Humans , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/mortality , Immunologic Deficiency Syndromes/virology , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/immunology , Prognosis , Purines/therapeutic use , Pyrazoles/therapeutic use , Risk Factors , SARS-CoV-2/pathogenicity , Sulfonamides/therapeutic use , Survival Analysis , Treatment Outcome
9.
Allergy Asthma Proc ; 42(6): 522-529, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1533596

ABSTRACT

Background: There are conflicting data with regard to the impact of respiratory and allergic comorbidities on the course of novel coronavirus disease 2019 (COVID-19) in children. Objective: This study aimed to investigate the relationship between allergic diseases and COVID-19 severity in pediatric patients. Methods: Seventy-five pediatric patients with COVID-19 were classified according to clinical severity and evaluated in the allergy/immunology and pulmonology departments 1 to 3 months after the infection resolved. Blood was collected from the patients for a complete blood cell count and assessment of immunoglobulin and total immunoglobulin E (IgE) levels, and skin-prick tests and spirometry tests were performed. Results: A total of 75 patients ages 5-18 years were evaluated. COVID-19 was asymptomatic/mild in 44 patients and moderate/severe/critical in 31 patients. Based on allergy evaluation, allergic rhinitis was diagnosed in 19 patients (25.3%), asthma in 10 patients (13%), and atopic dermatitis in 3 patients (4%). Aeroallergen sensitivity was detected in 26 patients (34.7%). COVID-19 infection was asymptomatic/mild in 15 patients with allergic rhinitis (78.9%) and in 21 with aeroallergen sensitivity (80.8%) (p = 0.038 and p = 0.005, respectively). There was no difference in severity between the patients with and without asthma (p = 0.550). The median (interquartile range) total IgE level was significantly higher in the asymptomatic/mild group (71.8 [30.7-211.2]) (p = 0.015). There were no differences in terms of spirometry parameters. Conclusion: Aeroallergen sensitization and allergic rhinitis in children may be associated with a milder course of COVID-19. The knowledge that atopy is associated with less-severe COVID-19 outcomes in children may guide clinical risk classification.


Subject(s)
Allergens/adverse effects , Asthma/diagnosis , COVID-19/complications , Dermatitis, Atopic/diagnosis , Hypersensitivity/diagnosis , Rhinitis, Allergic/diagnosis , Skin Tests/statistics & numerical data , Adolescent , Asthma/epidemiology , Asthma/immunology , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Dermatitis, Atopic/epidemiology , Dermatitis, Atopic/immunology , Female , Humans , Hypersensitivity/epidemiology , Hypersensitivity/immunology , Immunoglobulin E/blood , Male , Respiratory Function Tests , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/immunology , SARS-CoV-2 , Severity of Illness Index , Turkey/epidemiology
10.
Int Immunopharmacol ; 102: 108390, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1525826

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the impact of asthma on the risk for mortality among coronavirus disease 2019 (COVID-19) patients in the United States by a quantitative meta-analysis. METHODS: A random-effects model was used to estimate the pooled odds ratio (OR) with corresponding 95% confidence interval (CI). I2 statistic, sensitivity analysis, Begg's test, meta-regression and subgroup analyses were also performed. RESULTS: The data based on 56 studies with 426,261 COVID-19 patients showed that there was a statistically significant association between pre-existing asthma and the reduced risk for COVID-19 mortality in the United States (OR: 0.82, 95% CI: 0.74-0.91). Subgroup analyses by age, male proportion, sample size, study design and setting demonstrated that pre-existing asthma was associated with a significantly reduced risk for COVID-19 mortality among studies with age ≥ 60 years old (OR: 0.79, 95% CI: 0.72-0.87), male proportion ≥ 55% (OR: 0.79, 95% CI: 0.72-0.87), male proportion < 55% (OR: 0.81, 95% CI: 0.69-0.95), sample sizes ≥ 700 cases (OR: 0.80, 95% CI: 0.71-0.91), retrospective study/case series (OR: 0.82, 95% CI: 0.75-0.89), prospective study (OR: 0.83, 95% CI: 0.70-0.98) and hospitalized patients (OR: 0.82, 95% CI: 0.74-0.91). Meta-regression did reveal none of factors mentioned above were possible reasons of heterogeneity. Sensitivity analysis indicated the robustness of our findings. No publication bias was detected in Begg's test (P = 0.4538). CONCLUSION: Our findings demonstrated pre-existing asthma was significantly associated with a reduced risk for COVID-19 mortality in the United States.


Subject(s)
Asthma/epidemiology , COVID-19/mortality , Asthma/drug therapy , Asthma/immunology , COVID-19/immunology , COVID-19/virology , Humans , Prevalence , Prospective Studies , Protective Factors , Retrospective Studies , SARS-CoV-2/immunology , United States/epidemiology
11.
Acta Med Acad ; 49(2): 130-143, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1414828

ABSTRACT

In this review, we discuss the latest developments in research pertaining to virus-induced asthma exacerbations and consider recent advances in treatment options. Asthma is a chronic disease of the airways that continues to impose a substantial clinical burden worldwide. Asthma exacerbations, characterised by an acute deterioration in respiratory symptoms and airflow obstruction, are associated with significant morbidity and mortality. These episodes are most commonly triggered by respiratory virus infections. The mechanisms underlying the pathogenesis of virus-induced exacerbations have been the focus of extensive biomedical research. Developing a robust understanding of the interplay between respiratory viruses and the host immune response will be critical for developing more efficacious, targeted therapies for exacerbations. CONCLUSION: There has been significant recent progress in our understanding of the mechanisms underlying virus-induced airway inflammation in asthma and these advances will underpin the development of future clinical therapies.


Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antiviral Agents/therapeutic use , Asthma/drug therapy , Respiratory Tract Infections/drug therapy , Virus Diseases/drug therapy , Adenovirus Infections, Human/drug therapy , Adenovirus Infections, Human/immunology , Adenovirus Infections, Human/physiopathology , Administration, Inhalation , Asthma/immunology , Asthma/physiopathology , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Disease Progression , Humans , Influenza, Human/drug therapy , Influenza, Human/immunology , Influenza, Human/physiopathology , Interferon-beta/therapeutic use , Macrolides/therapeutic use , Omalizumab/therapeutic use , Paramyxoviridae Infections/drug therapy , Paramyxoviridae Infections/immunology , Paramyxoviridae Infections/physiopathology , Picornaviridae Infections/drug therapy , Picornaviridae Infections/immunology , Picornaviridae Infections/physiopathology , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Tract Infections/immunology , Respiratory Tract Infections/physiopathology , Virus Diseases/immunology , Virus Diseases/physiopathology
13.
Curr Opin Allergy Clin Immunol ; 21(6): 597-601, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1429314

ABSTRACT

PURPOSE OF REVIEW: As of June 2021, coronavirus disease 2019 (COVID-19) exceeded 180 million reported cases and was responsible for almost 4 million deaths globally. Asthma affects approximately 262 million people worldwide and is an important cause of morbidity and mortality. Presently, it appears asthma is neither associated with an increased risk of contracting COVID-19 nor with a risk of severe COVID-19 or COVID-19 related death. Regarding the severe asthma patients on biologics, questions remain. The purpose of this review is to discuss the evidence regarding the relationship between asthma, biologics and COVID-19. RECENT FINDINGS: The available evidence does not suggest that severe asthmatics on treatment with biologics have a higher risk of severe acute respiratory syndrome coronavirus 2 infection compared to the general population. It does not appear that they have a higher risk of severe disease or COVID-19 related death either. SUMMARY: This review suggests that treatment with biologics for severe asthma is safe and should be maintained during the COVID-19 pandemic. However, more studies are needed to address this question and the role of biological therapy on different asthma phenotypes.


Subject(s)
Asthma/drug therapy , Biological Products/adverse effects , COVID-19/immunology , Immunologic Factors/adverse effects , SARS-CoV-2/immunology , Asthma/diagnosis , Asthma/immunology , Biological Products/administration & dosage , COVID-19/diagnosis , COVID-19/mortality , Humans , Immunologic Factors/administration & dosage , Risk Assessment/statistics & numerical data , Risk Factors , Severity of Illness Index
15.
Clin Exp Allergy ; 50(10): 1122-1126, 2020 10.
Article in English | MEDLINE | ID: covidwho-1388225

ABSTRACT

Human coronaviruses (HCoVs) such as HCoV-229E or OC43 are responsible for mild upper airway infections, whereas highly pathogenic HCoVs, including SARS-CoV, MERS-CoV and SARS-CoV-2, often evoke acute, heavy pneumonias. They tend to induce immune responses based on interferon and host inflammatory cytokine production and promotion of T1 immune profile. Less is known about their effect on T2-type immunity. Unlike human rhinoviruses (HRV) and Respiratory Syncytial Virus (RSV), HCoVs are not considered as a dominant risk factor of severe exacerbations of asthma, mostly T2-type chronic inflammatory disease. The relationship between coronaviruses and T2-type immunity, especially in asthma and allergy, is not well understood. This review aims to summarize currently available knowledge about the relationship of HCoVs, including novel SARS-CoV-2, with asthma and allergic inflammation.


Subject(s)
Asthma/immunology , COVID-19/immunology , Hypersensitivity/immunology , SARS-CoV-2/immunology , Asthma/virology , Coronavirus/immunology , Humans , Hypersensitivity/virology
16.
Front Immunol ; 12: 678661, 2021.
Article in English | MEDLINE | ID: covidwho-1337638

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators. Methods: Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the "COVID-19 Drug and Gene Set Library" and with experimentally tested protein biomarkers of severe COVID-19. Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19. Conclusions: COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.


Subject(s)
Asthma/immunology , COVID-19/immunology , Inflammation Mediators/blood , Pulmonary Disease, Chronic Obstructive/immunology , SARS-CoV-2/physiology , Adult , Aged , Aged, 80 and over , Asthma/diagnosis , Biomarkers/blood , COVID-19/diagnosis , Chemokine CXCL9/blood , Female , Hepatocyte Growth Factor/blood , Humans , Interleukin-6/blood , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/diagnosis , Severity of Illness Index , Up-Regulation
17.
Neurosci Lett ; 760: 136042, 2021 08 24.
Article in English | MEDLINE | ID: covidwho-1262947

ABSTRACT

The airways are constantly exposed to a multitude of inhaled particles and, as such, require a finely tuned discrimination between harmful or potentially threatening stimuli, and discrete responses to maintain homeostasis. Both the immune and nervous systems have the ability to sense environmental (and internal) signals, to integrate the obtained information and to initiate a protective reaction. Lung immunity and innervation are known to be individually involved in these processes, but it is becoming clear that they can also influence one another via a multitude of complex mechanisms. Here, we specifically describe how sensory innervation affects airways immunity with a focus on pathological conditions such as asthma or infections, describing cellular and molecular mechanisms, and highlighting potentially novel therapeutic targets.


Subject(s)
Asthma/immunology , Neuroimmunomodulation , Respiratory System/immunology , Respiratory Tract Infections/immunology , Sensory Receptor Cells/metabolism , Animals , Disease Models, Animal , Humans , Respiratory System/innervation
18.
Viruses ; 12(10)2020 10 17.
Article in English | MEDLINE | ID: covidwho-1305816

ABSTRACT

Accurate detection of human respiratory viral infections is highly topical. We investigated how strongly inflammatory biomarkers (FeNO, eosinophils, neutrophils, and cytokines in nasal lavage fluid) and lung function parameters change upon rhinovirus 16 infection, in order to explore their potential use for infection detection. To this end, within a longitudinal cohort study, healthy and mildly asthmatic volunteers were experimentally inoculated with rhinovirus 16, and time series of these parameters/biomarkers were systematically recorded and compared between the pre- and post-infection phases of the study, which lasted two months and one month, respectively. We found that the parameters'/biomarkers' ability to discriminate between the infected and the uninfected state varied over the observation time period. Consistently over time, the concentration of cytokines, in nasal lavage fluid, showed moderate to very good discrimination performance, thereby qualifying for disease progression monitoring, whereas lung function and FeNO, while quickly and non-invasively measurable using cheap portable devices (e.g., at airports), performed poorly.


Subject(s)
Asthma/immunology , Asthma/virology , Inflammation/diagnosis , Picornaviridae Infections/diagnosis , Respiratory Tract Infections/virology , Adult , Biomarkers/analysis , Cytokines/immunology , Female , Humans , Inflammation/virology , Longitudinal Studies , Male , Nose/immunology , Picornaviridae Infections/immunology , Picornaviridae Infections/virology , Prospective Studies , Respiratory Function Tests , Respiratory Tract Infections/diagnosis , Rhinovirus , Young Adult
19.
Int J Mol Sci ; 22(13)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288907

ABSTRACT

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.


Subject(s)
Eosinophils/physiology , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Asthma/immunology , Asthma/pathology , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/immunology , Eosinophilic Esophagitis/pathology , Eosinophils/cytology , Eosinophils/immunology , Exosomes/metabolism , Extracellular Traps/metabolism , Humans , Plasma Cells/cytology , Plasma Cells/metabolism , SARS-CoV-2/isolation & purification
20.
Viruses ; 13(6)2021 06 05.
Article in English | MEDLINE | ID: covidwho-1259626

ABSTRACT

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate, and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location, and disease endotype. We found sexual dimorphism in the expression of SARS-CoV-2-related genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2, and TMPRSS4, were highly upregulated in both sexes. Overall, changes in SARS-CoV-2-related gene expression were specific to the Th2 high molecular endotype of asthma and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors wascorrelated with loss of club and ciliated cells in Th2 high asthma. Meanwhile, the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) was associated with increased goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype, and changes in epithelial heterogeneity as potential factors underlying asthmatic susceptibility, or lack thereof, to SARS-CoV-2.


Subject(s)
Asthma/immunology , COVID-19/immunology , Coronavirus Infections/immunology , Epithelial Cells/virology , Gene Expression , Host Microbial Interactions , Influenza, Human/immunology , Severity of Illness Index , Asthma/genetics , Asthma/virology , COVID-19/genetics , Coronavirus 229E, Human/genetics , Coronavirus 229E, Human/immunology , Coronavirus Infections/genetics , Epithelial Cells/classification , Female , Gene Expression Profiling , Host Microbial Interactions/genetics , Host Microbial Interactions/immunology , Humans , Influenza, Human/genetics , Male , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/immunology , Orthomyxoviridae/genetics , Orthomyxoviridae/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sex Characteristics
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