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1.
Chest ; 162(4):A602, 2022.
Article in English | EMBASE | ID: covidwho-2060644

ABSTRACT

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: We present two cases of symptomatic post-COVID eosinophilic pneumonia responsive to steroids. CASE PRESENTATION: Case 1: A 73-year-old gentleman with underlying asymptomatic rheumatoid arthritis (RA), was admitted with COVID pneumonia for which he received tocilizumab, remdesivir, and 12 days of dexamethasone. His course was complicated by MRSA pneumonia and bacteremia, so was discharged on IV Vancomycin. Six days post discharge, he redeveloped respiratory distress. Labs showed a WBC 18,000 and proBNP 2828. A chest CT revealed bilateral ground-glass opacities, worsening right upper lung airspace disease and bilateral pleural effusions. Despite receiving Furosemide, Vancomycin, and Ceftazidime, he required high-flow nasal cannula oxygenation (HFNC). Bronchoscopy demonstrated thick right bronchial secretions. BAL fluid revealed 7% eosinophils and grew MRSA. Case 2: A 70-year-old gentleman with extensive smoking history, emphysema, psoriasis, Guillain-Barré syndrome and a recent hospitalization for COVID pneumonia was discharged on a steroid taper. He returned 23 days post discharge in respiratory distress requiring HFNC, 5 days after discontinuing steroids. The chest CT revealed worsening fibrosis and bronchiectasis. Intravenous Levofloxacin and Vancomycin resulted in no clinical improvement. Bronchoscopy showed inflamed bronchi with secretions and BAL analysis revealed 6% eosinophils. For both patients, BAL was negative for fungi and PJP and CTA ruled out PE. Both patients were started on Prednisone with a prolonged taper. They improved clinically with decreased oxygen requirements to 4L nasal cannula and dramatic decrease in subjective dyspnea within 48 hours of starting steroids. DISCUSSION: The differential diagnosis for the clinical deterioration and worsening radiographs in both patients includes bacterial/fungal superinfection, PE, post-COVID-ILD and eosinophilic pneumonia. For the first patient, his RA was inactive. His BAL was positive for MRSA but did not improve until steroids were initiated. Neither of the patients were stable for VATS biopsy. Eosinophilic pneumonia is defined as pulmonary infiltrates with peripheral blood eosinophilia =500/ml, BAL eosinophils > 5% or eosinophilic infiltration on lung biopsy [1]. Both of our patients had >5% BAL eosinophils. Potentially, prolonged COVID-ILD stimulates T-Helper-2 cells, causing the release of IL-4/5/13 with recruitment of eosinophils. Studies report post-COVID-ILD biopsies show organizing pneumonia and fibrosis but have not yet been associated with eosinophilia. In both patients, we observed eosinophilia on BAL. It can be hypothesized that a delayed inflammatory response mediated by eosinophils play a role. CONCLUSIONS: Pulmonary eosinophilic pneumonia is a complication of post-COVID-ILD and can be successfully managed with steroids. Reference #1: De Giacomi F, Vassallo R, Yi ES, Ryu JH. Acute Eosinophilic Pneumonia. Causes, Diagnosis, and Management. Am J Respir Crit Care Med. 2018 Mar 15;197(6):728-736. doi: 10.1164/rccm.201710-1967CI. PMID: 29206477. DISCLOSURES: No relevant relationships by farrukh ahmad No relevant relationships by Deborah Markowitz No relevant relationships by Dhiraj Shah No relevant relationships by Garima Singh No relevant relationships by Aakriti Soni

2.
Drug Safety ; 45(10):1156-1157, 2022.
Article in English | ProQuest Central | ID: covidwho-2044974

ABSTRACT

Introduction: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is characterized by a type 2 pattern of inflammation resulting in the production of some cytokines such as interleukin (IL)-4, IL5, and IL13. Options for treatment-resistant CRSwNP include aspirin desensitization, recurrent topic and systemic corticosteroid use, and functional endoscopic sinus surgery (FESS). However, frequent relapses after medical and surgical treatment have been observed. Thus, dupilumab, a human recombinant monoclonal IgG4 antibody, changes radically the treatment of CRSwNP because of its binding effects on major drivers of human type 2 inflammatory processes [1-3]. Considering its recent approval, it may be useful to evaluate its safety profile. Objective: The aim of this study was to describe better adverse drug reactions (ADRs) related to dupilumab in the treatment of CRSwNP analyzing all individual case safety reports (ICSRs) collected into the European Spontaneous Reporting System (SRS) database. Methods: All ICSRs recorded starting from the drug approval up to 31 December 2021 with dupilumab reported as suspected and having the specific indication of CRSwNP were considered. A descriptive analysis was conducted to assess demographic characteristics and dupilumab-related variables. Results: Out of 10,400 ICSRs related to dupilumab, only 481 (4.6%) had CRSwNP indication, of which 68.2% were related to adults and 54.3% to females. The 68.4% were serious;however, ICSRs mainly led to a completely or partial recovering (25.4%) and 8 cases were fatal (1.7%). The time to onset (TTO) of ADRs was 25 (1-84.75) days while the time to resolution (TTR) was 5 (1.75-15.75) days. Analyzing ADRs by System Organ Classes (SOCs), the most reported were general and administration site conditions (36.4%) followed by injuries (21.6%), infections (21.2%), respiratory (19.1%), skin (16.6%), and nervous system disorders (16.4%). Looking at Preferred Terms (PTs), arthralgia (7.3%), eosinophilia (6.9%), COVID-19 (6.0%), pyrexia (5.8%), asthenia (5.6%), rash (5.4%), and dyspnoea (5.2%) were the most reported. The 7.5% of ICSRs described an aggravated condition with persistent nasal polyps: in 4 cases (0.8%) a nasal polypectomy was required. Considering fatal ICSRs, two cases were related to progression of COVID-19, one to road traffic accident, one to accidental death and the others were not fully specified. Conclusion: These results showed that dupilumab-related ICSRs are not commonly reported in CRSwNP. However, given the good treatment response and the minimal adverse effects observed, clinicians should consider treating CRSwNP with dupilumab. Moreover, additional analyses are necessary to better outline the safety profile of dupilumab in this particular setting.

3.
Front Immunol ; 13: 945063, 2022.
Article in English | MEDLINE | ID: covidwho-2032774

ABSTRACT

Type 2 helper T (Th2) cells, a subset of CD4+ T cells, play an important role in the host defense against pathogens and allergens by producing Th2 cytokines, such as interleukin-4 (IL-4), IL-5, and IL-13, to trigger inflammatory responses. Emerging evidence reveals that Th2 cells also contribute to the repair of injured tissues after inflammatory reactions. However, when the tissue repair process becomes chronic, excessive, or uncontrolled, pathological fibrosis is induced, leading to organ failure and death. Thus, proper control of Th2 cells is needed for complete tissue repair without the induction of fibrosis. Recently, the existence of pathogenic Th2 (Tpath2) cells has been revealed. Tpath2 cells produce large amounts of Th2 cytokines and induce type 2 inflammation when activated by antigen exposure or tissue injury. In recent studies, Tpath2 cells are suggested to play a central role in the induction of type 2 inflammation whereas the role of Tpath2 cells in tissue repair and fibrosis has been less reported in comparison to conventional Th2 cells. In this review, we discuss the roles of conventional Th2 cells and pathogenic Th2 cells in the sequence of tissue inflammation, repair, and fibrosis.


Subject(s)
Cytokines , Th2 Cells , Allergens , Fibrosis , Humans , Inflammation
4.
Annals of the Rheumatic Diseases ; 81:927-928, 2022.
Article in English | EMBASE | ID: covidwho-2008837

ABSTRACT

Background: Comorbidities, particularly cardio-metabolic disorders, are highly prevalent in patients with psoriatic arthritis (PsA) and they were associated with an increased risk of atherosclerotic cardiovascular disease, which have been associated with higher morbidity and mortality. Whether PsA enhances the risk of SARS-CoV-2 infection or affects the disease outcome remains to be ascertained. Objectives: To describe the sociodemographic, clinical and treatment characteristics of patients with PsA with confrmed SARS-CoV-2 infection from the SAR-COVID registry and to identify the variables associated with poor COVID-19 outcomes, comparing them with those with rheumatoid arthritis (RA). Methods: Cross-sectional observational study including patients ≥18 years old, with diagnosis of PsA (CASPAR criteria) and RA (ACR/EULAR 2010 criteria), who had confrmed SARS-CoV-2 infection (RT-PCR or serology) from the SAR-COVID registry. Recruitment period was between August 13, 2020 and July 31, 2021. Sociodemographic variables, comorbidities, and treatments were analyzed. To assess the severity of the infection, the ordinal scale of the National Institute of Allergy and Infectious Diseases (NIAID)1 was used, and it was considered that a patient met the primary outcome, if they presented criteria of categories 5 or higher on the severity scale. For this analysis, Chi2 test, Fisher's test, Student's test or Wilcoxon test, and binomial logistic regression using NIAID>=5 as dependent variable were performed. Results: A total of 129 PsA patients and 808 with RA were included. Clinical characteristics are shown in Table 1. Regarding PsA treatment, 12.4% of PsA were receiving IL-17 inhibitors, 5.4% IL12-23 inhibitors, one patient apremilast and one abatacept. The frequency of NIAID≥5 was comparable between groups (PsA 19.5% vs RA 20.1%;p=0.976). (Figure 1). PsA patients with NIAID≥5 in comparison with NIAID<5 were older (58.6±11.4 vs 50±12.5;p=0.002), had more frequently hypertension (52.2% vs 23%;p=0.011) and dyslipidemia (39.1% vs 15%;p=0.017). In the multivariate analysis, age (OR 1.06;95% CI 1.02-1.11) was associated with a worse outcome of the COVID-19 (NIAID≥5) in patients with PsA, while those who received methotrexate (OR 0.34;95% CI 0.11-0.92) and biological DMARDs (OR 0.28;95% CI 0.09-0.78) had a better outcome. Conclusion: Although PsA patients have a higher frequency of cardiovascular and metabolic comorbidities than those with RA, the COVID-19 severity was similar. Most of the patients had mild SARS-CoV-2 infection and a low death rate.

5.
Pediatrics ; 149, 2022.
Article in English | EMBASE | ID: covidwho-2003414

ABSTRACT

Background: Most children exposed to SARS-CoV-2 virus present with mild symptoms, but some may experience severe illnesses such as Multisystem inflammatory syndrome (MISC) or respiratory failure. Currently there are no established biomarkers to predict progression to severe disease. Although specific serum cytokines have been found to be higher in adults with severe COVID-19, their role as predictors of severe disease in children remains unclear. Further, the role of salivary cytokines in COVID-19 associated inflammation is unknown. Our objective was to compare cytokine levels in saliva of children with and without severe disease due to SARS-CoV-2 infection. Methods: This prospective observational study, conducted at two tertiary children's hospitals, was supported by a grant from the National Institute of Health RADx Program. Children ≤ 18 years of age with symptoms due to SARS-CoV-2 infection (positive PCR test, serology or immunological link) were enrolled after informed consent. Severe cases were defined as the occurrence of any of the following within 30 days of testing: diagnosis of MISC or Kawasaki disease, requirement for >2L oxygen, inotropes, mechanical ventilation or ECMO, or death. A saliva sample was obtained through passive drool using MicroSAL kits (Oasis Diagnostics) and a viral transport medium (VTM-C19, Biomed). Abundance levels of six cytokines (TNFR1, IL13, IL-15, CCL7, CXCL10 and CXCL9) were measured in triplicate using microfluidic immunoassays (Ella, Protein Simple). Mean concentrations for each sample were determined against a standard curve and corrected for dilution. Levels of the six cytokines were compared between those with severe or nonsevere SARS-CoV-2 symptoms using a non-parametric t-test. The relationship between salivary levels of individual cytokines was assessed among children with severe and non-severe SARS-CoV2 using a Pearson correlation analysis Results: A total of 150 children were enrolled from 03/29/2021 to 05/30/2021 (mean age of 7.1 years ± 5.7 years, 54.6% females). Of the total, 38 (25.3%) children met criteria for severe SARS-CoV-2 infection. CXCL10 displayed significantly (fold change>2, p < 0.05) elevated levels in the saliva of children with severe SARS-CoV-2 (Figure 1). The relationship between levels of CXCL9 (MIG) and CXCL10 showed greater levels association (R2 = 0.93) in children with severe SARS-CoV-2 than in peers with non-severe SARS-CoV-2 (R2 = 0.65;Figure 2). Conclusion: In this preliminary analysis of salivary cytokines among children with SARS-CoV-2 infection, we found CXCL10 displayed differential expression with severe symptoms. These findings may provide critical information about the pathophysiology of severe SARS-CoV-2. Confirmation in further studies is necessary. Saliva concentrations of CXCL10 in children with severe SARSCoV-2 symptoms. The whisker box plots display salivary concentrations of CXCL10 in children with severe (green) and non-severe (red) SARS-CoV-2 infection as measured with next generation enzyme linked immunosorbent assay. Levels of CXCL10 (p < 0.01;fold change = 3.04) were elevated in children with severe SARS-CoV-2 symptoms on Wilcoxon testing. .

6.
Laryngo- Rhino- Otologie ; 101:S180, 2022.
Article in English | EMBASE | ID: covidwho-1967655

ABSTRACT

Introduction The use of biologics has been described as an effective therapy in phase 3 studies in severe CRSwNP. Relatively unexplored is the post-covid syndrome in CRSwNP patients. Method Case presentation. Results Presentation of a 75-year-old patient with CRSwNP, asthma, ASA intolerance and eosinophilic granulomatosis with polyangiitis. Drug therapy with daily 1-5 mg prednisolone oral and inhalation therapy with formoterol/ beclomethasone. In February 2021, the patient was diagnosed with SARS-CoV-2 infection. For four days, the patient was admitted to a hospital with pronounced physical weakness without respiratory insufficiency. Anosmia has long been known because of CRSwNP. After Covid-19 illness, the patient reported severe sleep impairment and a severe state of exhaustion compatible with a post-covid syndrome. In addition, the patient was impaired by a severe nasal obstruction. At presentation in the rhinological consultation 7 months after Covid-19 illness, severe nasal polyps (NP overall score 8) and anosmia were detected. Dupilumab therapy (anti IL-4/IL-13 antibody) was initiated for severe CRSwNP. In the course of 2 months, an improved quality of life with less nasal obstruction as well as a reduced NP overall score of 6 were shown. Furthermore, the sleep impairment and exhaustion of the patient did not improve. Conclusion Dupilumab therapy improves quality of life in patients with severe CRSwNP, which may be especially important in post-covid syndrome.

7.
Gastroenterology ; 162(7):S-1101-S-1102, 2022.
Article in English | EMBASE | ID: covidwho-1967409

ABSTRACT

Introduction: Increased inflammatory cytokines has been observed in COVID-19 patients and there is evidence showing an alteration in gut-microbiota composition. SARS-CoV-2 can cause gastrointestinal symptoms, such as diarrhea. Evidence of an altered gut-microbiota composition and cytokines levels in COVID-19 diarrhea patients is lacking. Objectives: To compare serum cytokine levels and gut microbiota between COVID-19 diarrhea (D-COVID- 19) and non-diarrhea (NonD-COVID-19) patients and non- COVID-19 controls (HC). Material and methods: We included 143 hospitalized COVID-19 patients (positive quantitative reverse transcription PCR) in a single University Hospital, and 53 ambulatory HC (negative rapid serological test) were included. Blood and stool samples were collected at hospital admission in COVID-19 patients and at the time of HC recruitment. 27- pro and anti-inflammatory cytokines (Bio-Plex Pro™, Bio- Rad) were measured. Gut microbiota composition and diversity profiles were characterized by sequencing the 16S rRNA gene V3-V4 region amplified using DNA extracted from stool samples. Bioinformatics analysis was performed with QIIME2 software. First, we compare cytokine levels between COVID- 19 and HC and then COVID-19 with and without diarrhea. All comparisons were adjusted for age, sex, and BMI with linear regression. Results: The mean age in COVID-19 patients was 54 +/- 15 years (F=50%) and 52 +/- 8 (F=62%) for HC. Diarrhea was present in 19 (13.29%) of COVID-19 patients. COVID-19 patients had significative higher levels of: IL- 1ra, IL-2, IL-6, IL-7, IL-8, IL-13, IP-10 and PDGF-bb. Significant lower values of: IL-9, FGF -basic, MIP-1β, TNF-α were observed in D-COVID-19 compared to NonD-COVID-19. COVID-19 patients had a significant reduction of bacterial species (p=0.0001), and diversity and complexity of the bacterial community (Shannon's index) (p=0.0001) compared to the HC. There was no difference between D-COVID-19 and NonD-COVID-19. There were also changes in the composition of the microbiota associated with COVID-19. At the phylum level, COVID-19 patients showed a significant decrease in Actinobacteria and Firmicutes, and an increase in Bacteroidetes. At species level, an increase of 4 species of the genus Bacteroides was observed in COVID-19 patients. 31 very diverse bacterial species were found, all decreased in D-COVID-19. Conclusions: An alteration in serum cytokine levels was observed between COVID-19 and HC. D-COVID-19 had a decrease in some proinflammatory cytokines. A significant decrease in richness and species diversity of gutmicrobiota was observed in COVID-19 patients compared to HC, but no significant differences were observed between D-COVID-19 and NonD-COVID-19. However, in D-COVID- 19, a decrease in some bacterial species was observed.(Table Presented)(Figure Presented)

8.
Anti-Infective Agents ; 20(2), 2022.
Article in English | EMBASE | ID: covidwho-1938561

ABSTRACT

Coronavirus disease-2019 (COVID-19) has gained much popularity not only in the Wuhan city of China but internationally also;in January 2020, the corona rapidly spread to many countries like the USA, Italy, Russia, India, Singapore, Pakistan, Thailand, Canada, Australia, England, and so on through passengers traveling to other countries. Corona patients can be cured with synthetic drugs, traditional herbal medicines (THM), use of Vitamin D and the quarantine approach. Different allopathic medicines, herbal extracts, and vitamin D have been observed to be useful in the treatment of novel coronavirus, like Remdesivir, hydroxychloroquine, Teicoplanin, Lopinavir+ Ritonavir, Ribavirin + corticosteroids, Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. Various antiviral drugs are used to treat COVID-19, alone or in combination with other medications like Interferon-α, Lopinavir + Ritonavir, Arbidol, corticosteroids, etc., and some herbal extracts;also quarantine approach and Vitamin D are used that not only cure the infection but also boost up our immunity. For this review article, different papers were searched on Google Scholar, Scopus, WHO’s website, PubMed, clinicaltrials.gov and other relevant scientific research websites. In this review article, we have discussed the current strategies that are being used to treat COVID-19. Along with allopathic drugs, some herbal extracts can also be used to treat this novel coronavirus, like Glycyrrhizin, Sanguisorbae radix, Acanthopanacis cortex, Sophorae radix, etc. and even vitamin D.

9.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927846

ABSTRACT

Introduction:Dupilumab is an anti-IL4R monoclonal antibody (mAb) with proven efficacy in severe eosinophilic asthma (SEA). We have previously identified that a suboptimal response to the eosinophil targeting anti-IL5/5R mAbs mepolizumab and benralizumab is seen in 27% and 14% of patients with SEA respectively1,2. The mechanism of this is not well-understood. It is unknown whether such patients respond in a clinically meaningful way following a switch to dupilumab. Methods:We performed a retrospective analysis of the clinical effectiveness of dupilumab (minimum 6 months treatment) in patients with SEA at our tertiary severe asthma centre who had failed to adequately respond to at least one of the anti-IL-5/5R mAbs. Change in the annualised exacerbation rate (AER), maintenance oral corticosteroids (mOCS) requirements, ACQ-6 and mAQLQ was recorded. Results:Thirty-two patients (mean age 41.2, 68.8% female, 71.9% atopic) were included in the analysis. 13/32(40.6%) had co-morbid nasal polyposis and 5/32(15.6%) had eczema. The baseline FeNO was 60ppb(IQR 39.6-87.5) and peak eosinophil count prior to any mAb was 0.6(IQR 0.5-0.9). 23/32(71.8%) were switched from benralizumab, of whom, 12/23(52.2%) had also failed to respond to at least one other anti-IL5 mAb previously. At six months, the daily median mOCS dose in those requiring mOCS at baseline (n=18) fell from 10mg(IQR 5-25mg) to 3mg(IQR 0-5mg), p≤0.001. 4/18(22%) were able to stop mOCS completely. Mean(SD) AER improved from 2.34(1.89) to 0.44(0.95), p≤0.001. There were also significant improvements in ACQ6 and mAQLQ that exceeded twice the MCID for both measures: mean (SD) ACQ6 improved from 3.04(1.26) to 1.82(1.28), p≤0.001;mAQLQ improved from 3.90(SD 1.40) to 5.36(SD 1.05), p≤0.001. Due to the COVID-19 pandemic, FEV1 data was only available for 8 patients. However, there was nonetheless a significant rise in FEV1 (%predicted) from 55.6% (9.78) to 68.5%(16.9), p=0.011. One patient discontinued dupilumab during the follow-up period. Conclusion: A minority of individuals with SEA have a suboptimal response to eosinophil targeted therapy with an anti-IL5/5R mAb. In these patients, we report significant clinical improvements following initiation with dupilumab suggesting an important role for the IL-4/-13 pathway in these patients. Further research is required to understand whether these patients represent a distinct subphenotype of T2-high asthma.

10.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927706

ABSTRACT

Rationale We have previously reported blocking the IL-25 receptor (IL-17RB) prevented viral increased allergic airways inflammation and this was associated with reduced lung viral load. To investigate IL-25 regulation of airway anti-viral immunity we hypothesised that IL-25 directly inhibits airway epithelial cell (AEC) type I/III interferon expression and antibody blockade of IL-25 in vivo boosts lung interferon expression and reduces lung viral load in parallel with reduced type 2 airway inflammation. Methods In vitro Immunofluorescence was used to visualise epithelial IL-25 and IL- 17RB proteins in endobronchial biopsies from patients with asthma and healthy subjects and in AEC differentiated at ALI. AEC from n = 14 donors with asthma were differentiated at the air-liquid interface (ALI) and infected with RV-A1, MOI=0.1. A subset of AECs was treated with anti-IL-25 mAb (LNR125) before infecting with RV-A1 or human coronavirus 229E. Differentiated AEC from healthy donors were treated with recombinant IL-25 protein and infected with RV-A1. Nanostring immune transcriptomic data expressed as digital mRNA counts for exact copy number or was expressed as log2 fold change ratio against -log10 Bejamini-Yekutieli-corrected p-values. In vivo 6- 8-week-old, BALB/c mice sensitised and intranasally challenged daily for 3 days with ovalbumin to induced allergic airways disease. A single subcutaneous injection of 250 μg LNR125 was administered during ovalbumin challenge. Mice were then infected i.n. with RV-A1, 6 hours after final allergen challenge. On day 1 and day 7 post-infection, BAL were collected, lung lobe tissue was collected for viral RNA and cytokine expression. Results IL-25 and IL-17RB were constitutively expressed at the apical surface of airway epithelium in biopsies and AEC cultures. RV infection increased IL-25 expression by AEC from asthmatic donors. LNR125 treatment reduced IL-25 mRNA and significantly increased RV induced IFN-β a and IFN-λ protein expression and this was confirmed by Nanostring transcriptomic analyses which also identified down-regulated type-2 immune genes CCL26 (eotaxin 3) and IL1RL1(IL-33 receptor). LN125 treatment also increased IFN-λ expression by 229E-infected differentiated AECs. IL-25 treatment increased viral load associated with 50% reduced expression of IFN-β and CXCL10 and 75% reduced IFN-λ. Allergen challenged, RV-infected mice treated with LNR125 had significantly increased BAL IFN-β protein and 60% reduction in lung viral load associated with reduced IL-25, IL-4, IL-5 and IL-13 BAL proteins compared to controls. Conclusion IL-25-induced inflammation combined with suppression of AEC anti-viral immunity identify IL-25 as a central mediator of viral asthma exacerbations and therefore a target for mAb-based treatment.

11.
Journal of Allergy and Clinical Immunology ; 149(2):525-530, 2022.
Article in English | EMBASE | ID: covidwho-1676783
12.
Comput Biol Med ; 143: 105297, 2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1670371

ABSTRACT

BACKGROUND: Interleukin 13 (IL-13) is an immunoregulatory cytokine, primarily released by activated T-helper 2 cells. IL-13 induces the pathogenesis of many allergic diseases, such as airway hyperresponsiveness, glycoprotein hypersecretion, and goblet cell hyperplasia. In addition, IL-13 inhibits tumor immunosurveillance, leading to carcinogenesis. Since elevated IL-13 serum levels are severe in COVID-19 patients, predicting IL-13 inducing peptides or regions in a protein is vital to designing safe protein therapeutics particularly immunotherapeutic. OBJECTIVE: The present study describes a method to develop, predict, design, and scan IL-13 inducing peptides. METHODS: The dataset experimentally validated 313 IL-13 inducing peptides, and 2908 non-inducing homo-sapiens peptides extracted from the immune epitope database (IEDB). A total of 95 key features using the linear support vector classifier with the L1 penalty (SVC-L1) technique was extracted from the originally generated 9165 features using Pfeature. These key features were ranked based on their prediction ability, and the top 10 features were used to build machine learning prediction models. Various machine learning techniques were deployed to develop models for predicting IL-13 inducing peptides. These models were trained, tested, and evaluated using five-fold cross-validation techniques; the best model was evaluated on an independent dataset. RESULTS: Our best model based on XGBoost achieves a maximum AUC of 0.83 and 0.80 on the training and independent dataset, respectively. Our analysis indicates that certain SARS-COV2 variants are more prone to induce IL-13 in COVID-19 patients. CONCLUSION: The best performing model was incorporated in web-server and standalone package named 'IL-13Pred' for precise prediction of IL-13 inducing peptides. For large dataset analysis standalone package of IL-13Pred is available at (https://webs.iiitd.edu.in/raghava/il13pred/) webserver and over GitHub link: https://github.com/raghavagps/il13pred.

13.
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
14.
Allergy: European Journal of Allergy and Clinical Immunology ; 76(SUPPL 110):449-450, 2021.
Article in English | EMBASE | ID: covidwho-1570373

ABSTRACT

Background: Asthma is a chronic respiratory disease, and respiratory viruses are well-known triggers for asthma exacerbations. The novel coronavirus named SARS-CoV-2, which causes COVID-19, can present with pulmonary symptoms. Several studies suggest that IL-13, an allergic asthma mediator, should prevent asthma exacerbations by SARS-CoV-2. The objective of this study was to evaluate the clinical behavior of patients with asthma during the COVID-19 pandemic. Asthma is a chronic respiratory disease, and respiratory viruses are well-known triggers for asthma exacerbations.The novel coronavirus named SARS-CoV-2, which causes COVID-19, can present with pulmonary symptoms.Several studies suggest that IL-13, an allergic asthma mediator, should prevent asthma exacerbations by SARS-CoV-2. The objective of this study was to evaluate the clinical behavior of patients with asthma during the COVID-19 pandemic. Method: This was a retrospective study of electronic medical records of adult asthmatic patients, being followed up in a tertiary service and who received telephone calls for rescheduling the face-to-face consultations, during the COVID-19 pandemic period.Demographic data, asthma symptoms, frequency of atopy, presence of comorbidities and symptoms related to coronavirus infection were analyzed. Patients were classified according to their history of asthma attacks. Results: Two hundred and seven patients were included, and of them, 165 patients (79.7%) were female, with a mean age of 53.3 years and asthma duration of 35 years. Atopy was confirmed in 156 patients (81.7%). The main comorbidities were obesity (32.9%), high blood pressure (47.3%), diabetes mellitus (17.4%) and emotional stress (68.1%). Of the total, 87 patients (42%) had acute symptoms, of which 20 (9.7%) sought emergency care and 15 of 20 patients (75%) were investigated for Covid-19, all of which were negative. Of the total, only 7 patients (3.4%) exacerbated and required systemic corticosteroids. During this study, the more frequent complaints among asthmatic patients with acute respiratory symptoms were dyspnea, cough, asthenia and headache when compared to those without a crisis (p < 0.05). Conclusion: This study found that asthmatic patients had a low prevalence of asthma exacerbation during the coronavirus pandemic period. Patients with acute symptoms may have been underdiagnosed for COVID-19, due to the low demand for emergency care. Previous atopy may act as a protective factor for COVID-19 in asthmatic patients.

15.
Journal of Cystic Fibrosis ; 20:S183, 2021.
Article in English | EMBASE | ID: covidwho-1554123

ABSTRACT

Background: Chronic lung inflammation affects the response to respiratory viruses such as SARS-CoV-2 in airway epithelia. Based on the pattern associated with disease endotype, airway inflammation can be simplified into type 2 and type 17. Half of asthmatics have type 2 high endotype driven by IL-13/IL-4 cytokine signaling that induces goblet cell metaplasia. Other inflammatory diseases such as cystic fibrosis, chronic bronchitis, and sarcoidosis are associated with the type 17 cytokines IL-17 and TNF-α. Recent case-control studies have suggested that asthma may protect against or at least not worsen SARS-CoV-2 infection. However, the effect of inflammation on COVID-19 outcomes is unclear. Although interferons and cytokine-driven inflammation may modulate antiviral response, epithelial remodeling might also affect susceptibility to viruses.We applied a singlecell RNA-seq approach to investigate responses to SARS-CoV-2 in primary human airway epithelia treated with inflammatory cytokines. We hypothesized that IL-13-induced type 2 inflammation and IL-17-induced type 17 inflammation would respond differently to SARS-CoV-2-infected human airway epithelia and that IL-13 would protect the epithelia from SARS-CoV-2 infection through goblet cell-secreted factors Methods: We infected primary human airway epithelia (n = 3 donors) grown at the air–liquid interface with 0.1 multiplicity of infection of SARSCoV- 2 and obtained viral titers and single-cell suspensions at 6 and 72 hours after infection. The epitheliawere pretreated with IL-13 or IL-17 plus TNF-α for a short (4 days) or long (56 days) course to differentiate the early effects of cytokine response from late goblet cell metaplasia that develops over weeks. We then performed single-cell RNA-seq to analyze viral transcripts Results: We found that IL-13, but not IL17 plus TNF-α, protected epithelia from SARS-CoV-2 at 72 hours after infection. Moreover, the protection seemed to be independent of interferons because interferon-stimulated genes, induced by short IL-13 exposure, failed to protect the epithelia from viral infection. Our analysis shows that the genes with the largest expression change in long-course IL-13-treated epithelia were mediated by the appearance of goblet cells andwere goblet-specific genes. Using our single-cell RNA-seq data, we analyzed how cytokines change response in each cell type after viral infection. We found that, when cells become infected, their response is not abnormal. Conclusion: IL-13 protects human airway epithelia from SARS-CoV-2 infection in vitro;the protective mechanism may involve secreted products from goblet cells. IL-13-treated airway epithelial cells have an otherwise normal response to SARS-CoV-2. Our findings suggest that products secreted by goblet cells may have potential therapeutic applications for respiratory viral diseases.

16.
Gene Rep ; 22: 101012, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1002539

ABSTRACT

Recently an outbreak that emerged in Wuhan, China in December 2019, spread to the whole world in a short time and killed >1,410,000 people. It was determined that a new type of beta coronavirus called severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) was causative agent of this outbreak and the disease caused by the virus was named as coronavirus disease 19 (COVID19). Despite the information obtained from the viral genome structure, many aspects of the virus-host interactions during infection is still unknown. In this study we aimed to identify SARS-CoV-2 encoded microRNAs and their cellular targets. We applied a computational method to predict miRNAs encoded by SARS-CoV-2 along with their putative targets in humans. Targets of predicted miRNAs were clustered into groups based on their biological processes, molecular function, and cellular compartments using GO and PANTHER. By using KEGG pathway enrichment analysis top pathways were identified. Finally, we have constructed an integrative pathway network analysis with target genes. We identified 40 SARS-CoV-2 miRNAs and their regulated targets. Our analysis showed that targeted genes including NFKB1, NFKBIE, JAK1-2, STAT3-4, STAT5B, STAT6, SOCS1-6, IL2, IL8, IL10, IL17, TGFBR1-2, SMAD2-4, HDAC1-6 and JARID1A-C, JARID2 play important roles in NFKB, JAK/STAT and TGFB signaling pathways as well as cells' epigenetic regulation pathways. Our results may help to understand virus-host interaction and the role of viral miRNAs during SARS-CoV-2 infection. As there is no current drug and effective treatment available for COVID19, it may also help to develop new treatment strategies.

17.
World Allergy Organ J ; 13(5): 100126, 2020 May.
Article in English | MEDLINE | ID: covidwho-380025

ABSTRACT

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.

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