Background: Diagnostic tests for allergy rely on detecting allergen-specific IgE. Component-resolved diagnostics incorporate multiple defined allergen components to improve the quality of diagnosis and patient care. Objective: To develop a new approach for determining sensitization to specific allergen components that utilizes fluorescent protein tetramers for direct staining of IgE on blood basophils by flow cytometry. Methods: Recombinant forms of Lol_p_1 and Lol_p_5 proteins from ryegrass pollen (RGP) and Api_m_1 from honeybee venom (BV) were produced, biotinylated and tetramerized with streptavidin-fluorophore conjugates. Blood samples from 50 RGP-allergic, 41 BV-allergic and 26 controls were incubated with fluorescent protein tetramers for flow cytometric evaluation of basophil allergen binding and activation. Results: Allergen tetramers bound to and activated basophils from relevant allergic patients but not controls. Direct fluorescence staining of Api_m_1 and Lol_p_1 tetramers had greater positive predictive values than basophil activation for BV and RGP allergy, respectively, as defined with receiver operator characteristics (ROC) curves. Staining intensities of allergen tetramers correlated with allergen-specific IgE levels in serum. Inclusion of multiple allergens coupled with distinct fluorochromes in a single tube assay enabled rapid detection of sensitization to both Lol_p_1 and Lol_p_5 in RGP-allergic patients and discriminated between controls, BV-allergic and RGP-allergic patients. Conclusion: Our novel flow cytometric assay, termed CytoBas, enables rapid and reliable detection of clinically relevant allergic sensitization. The intensity of fluorescent allergen tetramer staining of basophils has a high positive predictive value for disease and the assay can be multiplexed for a component-resolved and differential diagnostic test for allergy.
Background Specific IgE against a peanut 2S albumin (Ara h2 or 6) is the best predictor of clinically relevant peanut sensitization. However, sIgE levels of peanut allergic and those of peanut sensitized but tolerant patients partly overlap, highlighting the need for improved diagnostics to prevent incorrect diagnosis and consequently unnecessary food restrictions. Thus, we sought to explore differences in V(D)J gene transcripts coding for peanut 2S albumin-specific monoclonal antibodies (mAbs) from allergic and sensitized but tolerant donors Methods 2S albumin-binding B-cells were single-cell sorted from peripheral blood of peanut allergic (n=6) and tolerant (n=6) donors sensitized to Ara h2 and/or 6 (≥ 0.1 kU/l) and non-atopic controls (n=5). Corresponding heavy and light chain gene transcripts were heterologously expressed as mAbs and tested for specificity to native Ara h2 and 6. HCDR3 sequence motifs were identified by Levenshtein distances and hierarchically clustering. Results The frequency of 2S albumin-binding B-cells was increased in allergic (median: 0.01%) compared to tolerant (median: 0.006%) and non-atopic donors (median: 0.0015%, p=0.008). The majority of mAbs (74%, 29/39) bound specifically to Ara h2 and/or 6. Non-specific mAbs (9/10) were mainly derived from non-atopic controls. In allergic donors, 89% of heavy chain gene transcripts consisted of VH3-family genes, compared with only 54% in sensitized but tolerant and 63% of non-atopic donors. Additionally, certain HCDR3 sequence motifs were associated with allergy or tolerance upon hierarchical clustering of their Levenshtein distances. Conclusions HCDR3 sequence motifs associated with allergy or tolerance may support correct diagnosis of patients with suspected peanut allergy.
Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629)
Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 on childhood asthma outcomes. Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4-18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent.
Mast cells are (in)famous for their role in allergic diseases, but the physiological and pathophysiological roles of this ingenious cell are still not fully understood. Mast cells are important for homeostasis and surveillance of the human system, recognizing both endogenous and exogenous agents, which induce release of a variety of mediators acting on both immune and non-immune cells, including nerve cells, fibroblasts, endothelial cells, smooth muscle cells and epithelial cells. During recent years, clinical and experimental studies on human mast cells as well as experiments using animal models have resulted in many discoveries that help decipher the function of mast cells in health and disease. In this review we focus particularly on new insights into mast cell biology, with a focus on mast cell development, recruitment, heterogeneity and reactivity. We also highlight the development in our understanding of mast cell driven-diseases and discuss the development of novel strategies to treat such conditions.
Treatment of Chronic Spontaneous Urticaria With Benralizumab: Report of Primary Endpoint Per Protocol Analysis, and Exploratory EndpointsStandard treatments for chronic spontaneous urticaria (CSU) including the second-generation H1-antihistamines (SGAH) are often ineffective even with four-times the FDA-recommended dose.1,2Eosinophilic infiltrates and an abundance of interleukin-5 (IL5) in CSU lesions (hives) support a role for IL5 in the pathomechanism of CSU.3 Thus, the use of biologic therapies, e.g. benralizumab targeting IL5-receptor-α, in treating SGAH-resistant CSU was hypothesized.A repeated-measures, 24-week study was designed and conducted at an urticaria clinic to determine clinical efficacy of benralizumab in CSU. Twelve SGAH-unresponsive CSU patients (3 males, 9 females; 2 blacks, 10 whites; between ages 32-65 years) having a median daily Urticaria Activity Score (UAS7)4 of 4, and pruritus severity ≥2 were enrolled. After a baseline run-in period, subjects were treated with a subcutaneous placebo dose followed by benralizumab 30mg subcutaneously every month (×3 doses) followed by two off-medication monthly-visits. Subject-reported responses to UAS7 and CU-QoL questionnaires were recorded at the monthly visits. The primary and exploratory endpoints were the change in UAS7 and Chronic Urticaria Quality-of-Life Total Score (CUQoLTS) respectively, from 4 weeks after placebo dose (visit 2) to 4 weeks after last dose of benralizumab (visit 5). Nine subjects completed the study; three withdrew after the first benralizumab dose. An intent-to-treat (ITT) analysis (n=12) of the primary endpoint has been reported previously.5Per-protocol (PP) analysis (n=9) of the primary endpoint, and PP vs. ITT of the exploratory endpoint are reported here. It was presumed that lesions were not self-limiting, and any improvement in outcomes during the study were because of intervention. Non-responders to benralizumab were identified if at any time during the 16 weeks after the first benralizumab dose there was <40% improvement in UAS7 from baseline vs. responders if UAS7 was ≤6.The average duration of urticarial symptoms was 7.0 years. Baseline UAS7 and CUQoLTS ranged between 22-42 and 36-95 respectively. Both outcomes significantly improved at visit 5 vs. visit 2 in 7 of 9 (78%) subjects completing the study. The average difference (95% CL) between visit 2 and visit 5 for UAS7, was -15.5 (-4.1, -26.8, p=0.003) and for CUQoLTS, using ITT analysis, was-13.2 (-2.4, -24.0, p=0.0005) or, using PP analysis, was -11.6 (-0.8, -22.4, p=0.03) (Figure-1 ). Five responders reported no hives/pruritus (UAS7=0) at visit 5 or 6.Between responders and non-responders, the average age (51.6 vs. 53, p=0.9) and symptom duration (5 vs. 9 years, p=0.5) did not differ significantly. However, the adjusted mean UAS7 percentage difference, adjusted for symptom duration, age, and blood eosinophils (eos%), from visit 2 till visit 5 was -84% for responders and +7.5% for non-responders, p=0.0009 (Table-1) . The average baseline UAS7 was not statistically significant (27 vs. 37.5, p=0.5) between groups however, the baseline mean difference for eos% was -6±1 (p=0.001), and for basophil% was -1.2±0.2, p=0.02), which were not observed at visit 5 (eos%: 0±1, p=0.9; basophil%: 0.2±0.2, p=0.8) (Table-1 ). Thus, clinical improvement among responders was independent of baseline disease severity. Non-responsiveness to benralizumab, measured by changes in UAS7, are likely due to other mechanistic factors unrelated to eos% which are eliminated by blocking IL-5R with benralizumab(S-Figure-1) .UAS7 and CU-QoLTS values were significantly correlated (r2=0.9, p<0.0001) (S-Table-3) . CU-QoL components that improved significantly were the pruritus/wheal scores, urticarial interference with physical activities, sleep and spare time (S-Table-4) .This study supports the use of benralizumab for treatment of SGAH-unresponsive CSU. Benralizumab-related improvements in UAS7 and CUQoLTS reported here are similar to the efficacy of omalizumab in CSU reported in a previous study (S-Table-5) .6The sustained significant improvement in urticarial lesions based on subject-reported outcomes by benralizumab warrants further investigation of underlying biologic pathways to better elucidate the role of IL-5 in CSU.
Background: Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil-associated proteins to identify EoE diagnosis and predict esophageal eosinophilia. Methods: Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein-1 (MBP-1), galectin-10 (CLC/GAL-10), Eotaxin-2 and Eotaxin-3, and urine osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Results: 183 specimens were collected from 56 EoE patients and 15 non-EoE patient controls; 33 EoE patients had paired pre- and post-treatment specimens. Plasma (CLC/GAL-10, ECP, EDN, Eotaxin-3, MBP-1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL-10, Eotaxin-3, ECP, EDN, MBP-1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL-10, ECP, and MBP-1 were significantly decreased in patients with a good response to treatment compared to patients with a poor response. AEC, CLC/GAL-10, ECP, EDN, OPN, and MBP-1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment and atopy; AEC combined with MBP-1 best predicted the counts. Conclusions: We identified novel panels of eosinophil-associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from control and predicting esophageal eosinophil counts.
To the Editor,We appreciate the interest and comments of Soriano and Ancochea1 regarding our papers 2. Further to the suggestion that “it would be of interest to repeat their statistics conducted during the first wave of COVID-19, again with the current estimates during the ongoing second wave, or later ones”, we would like to emphasize that our geographical observation was a type of anecdotal evidence that contributed to formulating a hypothesis. In a previous paper, we found that after adjusting for potentially relevant country-level confounders, there was a negative ecological association between COVID-19 mortality and the consumption of cabbage and cucumber in European countries 3. In this study, we acknowledged that “As in any ecological study, any inference from the observed association should be made at the country level, as the possibility of ecological fallacy precludes inferences at the individual level; and that further testing in properly designed individual studies would be of interest”. Indeed, what would be useful is testing the hypothesis in robust observational studies and/or clinical trials.Regarding our observation that COVID-19 could be considered as a disease of the Anthropocene 4 , other authors have recently provided a more complete description of the links between the disruption of the natural ecosystems that characterize the Anthropocene and the occurrence of zoonosis 5 6.1. Soriano J and Ancochea J. Saved by cabbage, killed by cabbage, and COVID-19. Allergy 2020; in press.2. Bousquet J, Anto JM, Czarlewski W, et al. Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19. Allergy 2020. DOI: 10.1111/all.14549.3. Fonseca S, Rivas I, Romaguera D, et al. Association between consumption of vegetables and COVID-19 mortality at a country level in Europe. MedRix 2020; 10.1101/2020.07.17.201558464. O’Callaghan C and Anto J. COVID-19: The Disease of the Anthropocene.Env Res 2020; 187: 109683.doi: 109610.101016/j.envres.102020.109683. Epub 102020 May 109615.5. Morens DM and Fauci AS. Emerging Pandemic Diseases: How We Got to COVID-19. Cell 2020; 182: 1077-1092. 2020/08/28. DOI: 10.1016/j.cell.2020.08.021.6. Roche B, Garchitorena A, Guegan JF, et al. Was the COVID-19 pandemic avoidable? A call for a ”solution-oriented” approach in pathogen evolutionary ecology to prevent future outbreaks. Ecol Lett 2020 2020/09/02. DOI: 10.1111/ele.13586.JM AntoISGlobAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. IMIM (Hospital del Mar Research Institute), Barcelona, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Spain. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.J BousquetCharité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Berlin, Germany. MACVIA-France, Montpellier, France.
Groundbreaking Discoveries in ImmunologyTitle : IgE sialylation: unravelling a key anaphylactic mediatorAuthors : Beatriz Moyaa, Chiara Tontinib and Alexandra Santosc, d, e, fa. Allergy Service. Hospital Universitario 12 de Octubre, Madrid, Spainb. Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UKc. Department of Women and Children’s Health (Paediatric Allergy), School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UKd. Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, London, UKe. Children’s Allergy Service, Guy’s and St Thomas’ Hospital, London, UKf. Asthma UK Centre of Allergic Mechanisms of Asthma, London, UKCorrespondence to : Beatriz Moya. Allergy Service. Hospital Universitario 12 de Octubre, Madrid, SpainEmail: email@example.comAbbreviations: Ig, Immunoglobulin; Fab, antigen-binding fragments; Fc, fragment crystallizable region; FcεRI, Fc epsilon receptor I; MC, mast cells.Word count: 637/1000
Association between asthma and clinical mortality/morbidity in COVID-19 patients using clinical epidemiologic data from Korean Disease Control & PreventionHyo-Geun Choi1, Jee Hye Wee2, So Young Kim2, Joo-Hee Kim3, Hwan Il Kim3, Ji-Young Park3, Sunghoon Park3, Yong Il Hwang3, Seung Hun Jang3, and Ki-Suck Jung31 Departments of Otorhinolaryngology-Head & Neck Surgery, Hallym UniversitySacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea2 Department of Otorhinolaryngology-Head & Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea3 Division of Pulmonary, Allergy, and Critical Care Medicine, Department ofMedicine, Hallym University Sacred Heart Hospital, Hallym University Collegeof Medicine, Anyang, Korea
The coronavirus disease 2019 pandemic (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global social and economic impact, and numerous deaths. Many risk factors have been identified in the progression of COVID-19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung disease, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type-I interferon secretion capacity, and pregnancy. Possible complications include acute respiratory distress syndrome, shock, disseminated coagulopathy, acute kidney injury, pulmonary embolism, and secondary bacterial pneumonia. The development of lymphopenia and eosinopenia are laboratory indicators of COVID-19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high-sensitivity C-reactive protein, proinflammatory cytokines such as interleukin (IL)-6, IL-1, Krebs von den Lungen-6 (KL-6) and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of COVID-19.
The role of eosinophils in allergic inflammation is well recognized. In homeostasis these cells are found in multiple healthy tissues including the lung parenchyma, but the function of these resident eosinophils is unknown. Circulating eosinophils are easily quantifiable and have been used to define “eosinophilic phenotype”, and to select patients who are likely to respond to anti-eosinophil and anti-Th2—directed therapies. However, presence of eosinophils in circulation may not necessarily indicate that the eosinophils are key effector cells for an airway disease such as asthma and this may be reason for not all patients responding well to anti-IL5 therapies despite normalization of blood eosinophils. This pro-con commentary examines the role of enumerating circulating vs luminal (sputum) eosinophils (and their activation status) not only to initiate therapies with monoclonal antibodies, but to monitor their clinical response while on therapy.
IgE, the key molecule in atopy has been shown to bind two receptors, FcRI, the high affinity receptor and FcεRII (CD23), mostly found on B cells and that binds IgE with lower affinity. Whereas cross-linking of IgE on FcRI triggers allergic reaction, binding of IgE to CD23 is known to play an important role in both IgE synthesis and presentation. Thus, targeting IgE-immune complexes on B cells has shown to enhance antibody and T cell responses in mice and humans. However, the mechanisms that regulate the targeting of the two receptors and the respective function of the two pathways in inflammation or homeostasis are still matter of debate. Here, we discuss several mechanisms related to IgE and IgE binding to both receptors, as well as the influence of the antigen binding on different immune cells expressing the receptors. One recent paper has shown that free IgE preferentially binds to FcRI whereas IgE immune complexes (IgE-ICs) are preferentially captured by CD23. Binding of IgE-ICs to CD23 on B cells can on one hand regulate serum IgE and prevent effector cell activation and on the other hand facilitate the antigen presentation by delivering antigen to dendritic cells. The data suggest that CD23 play a multifunctional role in regulating the allergic response pathway.
Background: Breastfeeding is associated with long-term health benefits, such as a lower incidence of allergy, asthma, diabetes or celiac disease. However, little is known regarding how the maternal and neonatal immune systems interact after parturition when the neonate receives nutrition from maternal breastmilk. Methods: We undertook a comparative analysis of immune repertoire and function at birth and 3 weeks of age in a cohort of 38 term neonates born by caesarean section grouped according to feeding method (breastmilk versus formula). We used flow cytometry to study the immune phenotype in neonatal and maternal blood samples and mixed lymphocyte reactions to establish the proliferation response of neonatal versus maternal lymphocytes and vice versa. The microbiome of neonatal stool samples was also investigated using 16S rRNA sequencing. Results: We show that the proportion of regulatory T cells (Tregs) increases in this period and is nearly two-fold higher in exclusively breastfed neonates compared to those who received formula milk only. Moreover, breastfed neonates show a specific and Treg-dependent reduction in proliferative T cell responses to non-inherited maternal antigens (NIMA), associated with a reduction in inflammatory cytokine production. Conclusions: These data indicate that exposure of the neonate to maternal cells through breastfeeding acts to drive the maturation of Tregs and ‘tolerizes’ the neonate towards NIMA.
Purpose Tear fluid N-Glycome from patients affected with vernal (VKC) and atopic keratoconjunctivitis (AKC) was investigated to identify specific changes in tears and to recognize possible glyco-biomarkers. Methods The analysis of N-glycans was performed using matrix-assisted laser desorption ionization mass spectrometry on single tear samples. Tears from control normal subjects (CTRL), VKC and AKC patients were processed and treated with peptide N-glycosidase F (PNGase F) to deglycosylate N-glycoproteins. Released N-glycans were purified, permethylated and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry and tandem Mass Spectrometry (MALDI-TOF MS and MALDI-TOF MS/MS). Results More than 150 complex N-glycans, including highly fucosylated biantennary, triantennary, tetraantennary and bisecting species, were observed in our spectra. Three distinct patterns for CTRL, VKC and AKC patients were identified in terms of relative intensities for some N-glycans structures. Major variations involved bisecting and hyperfucosylated glycoforms. The most intense ions were associated to species at m/z 1907.0 (asialo, agalacto, bisected, biantennary structure – NGA2B) in CTRL MS profiles, at m/z 2605.3 and 2966.5 in VKC, and at m/z 2792.4 in AKC corresponding to a well-known biantennary, disialylated N-glycan. Several peaks were associated to structures bearing one or two Lewis X epitopes. Structures were confirmed by MS/MS analysis. Quantitative differences among the three groups were statistically significant. Conclusions Tear MS profiles are rich in specific glycoforms, particularly those with a high fucosylation degree, indicating both core and peripheral decoration. Tear N-glycome analysis provided important information for a better comprehension of VKC and AKC alterations at the molecular level
Background: Many arguments suggest that neutrophils could play a prominent role in COVID-19. However, the role of key components of neutrophil innate immunity in severe forms of COVID-19 has deserved insufficient attention. We aimed to evaluate the involvement of Neutrophil Elastase, histone-DNA, and DNases in systemic and multi-organ manifestations of COVID-19. Methods: We performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center (ambulatory subjects), local hospitals, and two regional university hospitals. The case were evaluated according to clinical and biological markers of severity and multi-organ manifestations and compared to 35 healthy controls. Results: Blood Neutrophil Elastase, histone-DNA, myeloperoxidase-DNA and free dsDNA were dramatically increased, and DNase activity decreased by 10-fold, compared to controls. Neutrophil Elastase and histone-DNA were associated with intensive care admission, body temperature, lung damage and markers of cardiovascular outcomes, renal failure and increased IL-6, IL-8 and CXCR2. Neutrophil Elastase was an independent predictor of the computed tomography score of COVID-19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease of blood DNase activity. Conclusion: Our results point out the key role of neutrophil innate immunity exacerbation in COVID-19. Neutrophil Elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID-19.
Adequate nasal breathing is indispensable for athletes and nasal symptoms have been shown to inter-fere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease and therefore adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symp-toms are more prevalent in athletes compared to the general population and certain sport environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on un-met needs for the management and prevention of these symptoms in athletes within the concept of precision medicine.