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  • Immune cells in bronchoalveolar lavage fluid of Ugandan adults who resist versus those who develop latent Mycobacterium tuberculosis infection
    medRxiv. Allergy Immunol. Pub Date : 2021-01-26
    Bonnie A Thiel; William Worodria; Sophie Nalukwago; Mary Nsereko; Ingvar Sanyu; Lalitha Rejani; Josephine Zawedde; David H Canaday; Catherine a Stein; Keith A Chervenak; LaShaunda L Malone; Ronald Kiyemba; Richard F Silver; John L Johnson; Harriet Mayanja-Kizza; W Henry Boom

    Background: The search for immune correlates of protection against Mycobacterium tuberculosis (MTB) infection in humans is limited by the focus on peripheral blood measures. Bronchoalveolar lavage (BAL) can safely be done and provides insight into cellular function in the lung where infection is first established. In this study, blood and lung samples were assayed to determine if heavily MTB exposed

  • Total predicted MHC-I epitope load is inversely associated with mortality from SARS-CoV-2
    medRxiv. Allergy Immunol. Pub Date : 2021-01-25
    Eric Wilson; Gabrielle Hirneise; Abhishek Singharoy; Karen S Anderson

    Polymorphisms in MHC-I protein sequences across human populations significantly impacts viral peptide binding capacity and thus alters T cell immunity to infection. Consequently, allelic variants of the MHC-I protein have been found to be associated with patient outcome to various viral infections, including SARS-CoV. In the present study, we assess the relationship between observed SARS-CoV-2 population

  • IL-1 and IL-6 inhibitor hypersensitivity link to common HLA-DRB1*15 alleles
    medRxiv. Allergy Immunol. Pub Date : 2021-01-17
    Jill A. Hollenbach; Michael J. Ombrello; Adriana H. Tremoulet; Gonzalo Montero-Martin; Sampath Prahalad; Scott Canna; Chisato Shimizu; Gail Deutsch; Serena Tan; Elaine F. Remmers; Dimitri Monos; Omkar K. Phadke; Jianpeng Xu; Jaime S Rosa Duque; Gilbert T Chua; Vamsee Mallajosyula; Ann Marie Szymanski; Danielle Rubin; Debopam Ghosh; Jane C Burns; Marcelo Fernandez-Vina; Elizabeth D Mellins; Vivian Saper

    Background: Drug reaction with eosinophilia and systemic symptoms (DRESS), a severe, delayed hypersensitivity reaction (DHR), is underrecognized, particularly in patients with inflammatory diseases. Atypical features arising during interleukin 1 (IL-1) and interleukin 6 (IL-6) inhibitor treatment of systemic onset juvenile arthritis (sJIA) and adult onset Stills disease (AOSD) suggested this serious

  • Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2021-01-15
    Jorge A. Masso-Silva; Alexander Moshensky; Michael T. Y. Lam; Mazen Odish; Arjun Patel; Le Xu; Emily Hansen; Samantha Trescott; Celina Nguyen; Roy Kim; Katherine Perofsky; Samantha Perera; Lauren Ma; Josephine Pham; Mark Rolfsen; Jarod Olay; John Shin; Jennifer M. Dan; Robert Abbott; Sydney Ramirez; Thomas H. Alexander; Grace Y. Lin; Ana Lucia Fuentes; Ira N. Advani; Deepti Gunge; Victor Pretorius;

    Background: Increased inflammation is a hallmark of COVID-19, with pulmonary and systemic inflammation identified in multiple cohorts of patients. Definitive cellular and molecular pathways driving severe forms of this disease remain uncertain. Neutrophils, the most numerous leukocytes in blood circulation, can contribute to immunopathology in infections, inflammatory diseases and acute respiratory

  • The Effect of Short Message Service (SMS)-Reminders on Child Health in Parents of Newborns: A Pilot Randomised Controlled Trial
    medRxiv. Allergy Immunol. Pub Date : 2021-01-13
    Mudra Shah; Jessica A Ramsay; Michael Dymock; Julie Marsh; Nelly Newall; Carly McCallum; Jonathan Davis; Thomas Snelling

    Background Incomplete vaccination in Australia is greatly due to vaccine hesitancy, which is driven by multiple factors. Studies analysing the effect of behavioural 'nudges' on vaccine uptake have shown promising results. Although there is some evidence for positively framed SMS vaccine messages, evidence is lacking for loss-based framed messages which may be highly effective but may paradoxically

  • Multi-organ complement deposition in COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2021-01-08
    Paolo Macor; Paolo Durigutto; Alessandro Mangogna; Rossana Bussani; Stefano D'Errico; Martina Zanon; Nicola Pozzi; Pier Luigi Meroni; Francesco Tedesco

    Background: Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at tissue level. The mechanisms and pathways of local complement activation remain unclear. Methods: We performed immunofluorescence analyses of autopsy specimens of lungs, kidney and liver from nine COVID-19 patients

  • Risk of acute arterial and venous thromboembolic events in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)
    medRxiv. Allergy Immunol. Pub Date : 2021-01-06
    Alessandra Bettiol; Italian EGPA Consortium

    Background and objective: Systemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based

  • Probabilistic approaches for classifying highly variable anti-SARS-CoV-2 antibody responses
    medRxiv. Allergy Immunol. Pub Date : 2021-01-06
    Xaquin Castro Dopico; Leo Hanke; Daniel J Sheward; Sandra Muschiol; Soo Aleman; Nastasiya F Grinberg; Murray Christian; Monika Adori; Laura Perez Vidakovics; Kim Chang Il; Sharesta Khoenkhoen; Pradeepa Pushparaj; Ainhoa Moliner Morro; Marco Mandolesi; Marcus Ahl; Mattias Forsell; Jonathan Coquet; Martin Corcoran; Joanna Rorbach; Joakim Dillner; Gordana Bogdanovic; Gerald Mcinerney; Tobias Allander;

    Antibody responses vary widely between individuals1, complicating the correct classification of low-titer measurements using conventional assay cut-offs. We found all participants in a clinically diverse cohort of SARS-CoV-2 PCR+ individuals (n=105), and n=33 PCR+ hospital staff, to have detectable IgG specific for pre-fusion-stabilized spike (S) glycoprotein trimers, while 98% of persons had IgG specific

  • Modelling Decay of Population Immunity With Proposed Second Dose Deferral Strategy
    medRxiv. Allergy Immunol. Pub Date : 2021-01-06
    Graham T Jurgens

    A second dose deferred strategy has been proposed to increase initial population immunity as an alternative to the default two dose vaccine regimen with spacing of 21 or 28 days between vaccine doses for the mRNA vaccines from Pfizer and Moderna. This increased initial population immunity is only of value if one dose immunity does not decay so fast as to nullify the benefit. Because decay rates of

  • Phenome-wide HLA association landscape of 235,000 Finnish biobank participants
    medRxiv. Allergy Immunol. Pub Date : 2020-12-29
    Jarmo Ritari; Satu Koskela; Kati Hyvarinen; FinnGen; Jukka Partanen

    The human leukocyte antigen (HLA) system is the single most important genetic susceptibility factor for many autoimmune diseases and immunological traits. However, in a range of clinical phenotypes the impact of HLA alleles or their combinations on the disease risk are not comprehensively understood. For systematic population-level analysis of HLA-phenotype associations we imputed the alleles of classical

  • Seropositivity in blood donors and pregnant women during 9-months of SARS-CoV-2 transmission in Stockholm, Sweden
    medRxiv. Allergy Immunol. Pub Date : 2020-12-26
    Xaquin C Dopico; Sandra Muschiol; Murray Christian; Leo Hanke; Daniel J Sheward; Nastasiya F Grinberg; Gordana Bogdanovic; Gerald Mcinerney; Tobias Allander; Chris Wallace; Ben Murrell; Jan Albert; Gunilla B Karlsson Hedestam

    Public health strategies to contain the pandemic continue to vary markedly across the world. In Sweden, compared to most advanced economies, social restrictions have primarily relied upon voluntary adherence to a set of recommendations and strict lockdowns have not been enforced. To better understand the development of humoral immunity to SARS-CoV-2 in the Stockholm population before the start of mass

  • Kinetics of antibody responses dictate COVID-19 outcome
    medRxiv. Allergy Immunol. Pub Date : 2020-12-22
    Carolina Lucas; Jon Klein; Maria Sundaram; Feimei Lu; Patrick Wong; Julio Silva; Tianyang Mao; Ji Eun Oh; Maria Tokuyama; Peiwen Lu; Arvind Venkataraman; Annsea Park; Benjamin Israelow; Anne Wyllie; Chantal Vogels; M. Catherine Muenker; Arnau Casanovas-Massana; Wade Schulz; Joseph Zell; Melissa Campbell; John Fournier; Nathan Grubaugh; Charles Dela Cruz; Shelli Farhadian; Adam Wisnewski; Saad Omer;

    Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and

  • Immune Cell Profiles and Cytokine Levels of Patients with Interstitial Cystitis/Bladder Pain Syndrome.
    medRxiv. Allergy Immunol. Pub Date : 2020-12-19
    Robert M. Moldwin; Vishaan Nursey; Oksana Yaskiv; Siddhartha Dalvi; Michael Funaro; William DeGouveia; Marina Ruzimovsky; Horacio R. Rilo; Edmund J. Miller; Souhel Najjar; Inna Tabansky; Joel N.H. Stern

    Aims: To quantify the number of immune cells in the bladder urothelium and concentrations of urinary cytokines in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). To identify differences in these measures in IC/BPS patients with Hunner's lesions (IC/BPS-HL) and without Hunner's lesions (IC/BPS-NHL). Methods: Bladder tissue biopsies were obtained from 48 patients with IC/BPS-HL and

  • CD177, a specific marker of neutrophil activation, is a hallmark of COVID-19 severity and death
    medRxiv. Allergy Immunol. Pub Date : 2020-12-14
    Yves Levy; Aurelie Wiedemann; Boris P Hejblum; Melany Durand; Cecile Lefebvre; Mathieu Surenaud; Christine Lacabaratz; Matthieu Perreau; Emile Foucat; Marie Dechenaud; Pascaline Tisserand; Fabiola Blengio; Benjamin Hivert; Marine Gautier; Minerva Cervantes; Delphine Bachelet; Cedric Laouenan; lila Bouadma; Jean-Francois Timsit; Yazdan Yazdanpanah; Giuseppe Pantaleo; Hakim Hocini; Rodolphe Thiebaut;

    COVID-19 SARS-CoV-2 infection exhibits wide inter-individual clinical variability, from silent infection to severe disease and death. The identification of high-risk patients is a continuing challenge in routine care. We aimed to identify factors that influence clinical worsening. We analyzed 52 cell populations, 71 analytes, and RNA-seq gene expression in the blood of severe patients from the French

  • Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins
    medRxiv. Allergy Immunol. Pub Date : 2020-12-11
    Yang Li; Zhaowei Xu; Qing Lei; Danyun Lai; Hongyan Hou; Hewei Jiang; yunxiao Zheng; Xuening Wang; Jiaoxiang Wu; Mingliang Ma; Bo Zhang; Hong Chen; Caizheng Yu; Junbiao Xue; Nainang Zhang; Huan Qi; Shujuan Guo; Yandi Zhang; Xiaosong Lin; Zongjie Yao; Huiming Sheng; Ziyong Sun; Feng Wang; Xionglin Fan; Sheng-ce Tao

    The immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp

  • An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis
    medRxiv. Allergy Immunol. Pub Date : 2020-12-08
    Kan Zhang; Yuchen Feng; Yuxia Liang; Wenliang Wu; Chenli Chang; Dian Chen; Shengchong Chen; Jiali Gao; Gongqi Chen; Lingling Yi; Dan Cheng; Guohua Zhen

    Introduction: Epithelial cell-derived cytokines IL-25, IL-33 and TSLP initiate type 2 inflammation in allergic diseases. However, the signaling pathway regulating these cytokines expression remains elusive. We examined the role of epithelial microRNAs in the expression of IL-25, IL-33 and TSLP in asthma. Methods: Differentially expressed epithelial microRNAs between type 2-low and type 2-high asthma

  • Distinct impact of IgG subclass and Fc-FcγR interaction on autoantibody pathogenicity in different IgG4-mediated diseases
    medRxiv. Allergy Immunol. Pub Date : 2020-12-08
    Yanxia Bi; Jian Su; Shengru Zhou; Yingjie Zhao; Yan Zhang; Huihui Zhang; Mingdong Liu; Aiwu Zhou; Meng Pan; Yiming Zhao; Fubin Li

    IgG4 is the least potent human IgG subclass for the FcγR-mediated antibody effector function and is considered anti-inflammatory in the context of prolonged inflammation and allergic responses. Paradoxically, IgG4 is also the dominant IgG subclass of pathogenic autoantibodies in IgG4-mediated diseases. Here we show that the IgG subclass and Fc-FcγR interaction have a distinct impact on the pathogenic

  • Seroconversion stages COVID19 into distinct pathophysiological states
    medRxiv. Allergy Immunol. Pub Date : 2020-12-07
    Matthew D. Galbraith; Kohl T. Kinning; Kelly D Sullivan; Ryan Baxter; Paula Araya; Kimberly R Jordan; Seth Russell; Keith P Smith; Ross E Granrath; Jessica R Shaw; Monika Dzieciatkowska; Tusharkanti Ghosh; Andrew A Monte; Angelo D'Alessandro; Kirk C Hansen; Tellen D Bennett; Elena W.Y. Hsieh; Joaquin M Espinosa

    COVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results

  • Impact of the COVID-19 pandemic on infant and pediatric asthma: a multi-center survey using an administrative database in Japan
    medRxiv. Allergy Immunol. Pub Date : 2020-12-07
    Seiko Bun; Kenji Kishimoto; Jung-ho Shin; Daisuke Takada; Tetsuji Morishita; Susumu Kunisawa; Yuichi Imanaka

    Background Limited data are available on the relationship between infant and pediatric asthma and severe acute respiratory syndrome coronavirus 2 (COVID-19). Political limitations such as school closure may affect the treatment behavior of pediatric asthma. To investigate the trends of treatment behavior in the field of pediatrics during the COVID-19 pandemic. Methods This is a retrospective observational

  • Can serum biomarkers predict the outcome of systemic therapy for atopic dermatitis?
    medRxiv. Allergy Immunol. Pub Date : 2020-12-04
    Guillem Hurault; Evelien Roekevisch; Mandy E Schram; Krisztina Szegedi; Sanja Kezic; Maritza A Middelkamp-Hup; Phyllis I Spuls; Reiko J Tanaka

    Background: Atopic dermatitis (AD or eczema) is a most common chronic skin disease. Designing personalised treatment strategies for AD based on patient stratification, rather than the one-size-fits-all treatments, is of high clinical relevance. It has been hypothesised that the measurement of biomarkers could help predict therapeutic response for individual patients. Objective: We aim to assess whether

  • SARS-CoV-2 serology in 4000 health care and administrative staff across seven sites in Lombardy, Italy
    medRxiv. Allergy Immunol. Pub Date : 2020-12-02
    Maria Teresa Sandri; Elena Azzolini; Valter Torri; Sara Carloni; Chiara Pozzi; Michela Salvatici; Michele Tedeschi; Massimo Castoldi; Alberto Mantovani; Maria Rescigno

    Lombardy is the Italian region most affected by COVID-19. We tested the presence of plasma anti-SARS-CoV-2 IgG antibodies in 3985 employees across 7 healthcare facilities in areas of Lombardy with different exposure to the SARS-CoV-2 epidemic. Subjects filled a questionnaire to self-report on COVID-19 symptoms, co-morbidities, smoking, regular or smart-working, and the exposure to COVID-infected individuals

  • Impact of environmental factors in predicting daily severity scores of atopic dermatitis
    medRxiv. Allergy Immunol. Pub Date : 2020-12-02
    Guillem Hurault; Valentin Delorieux; Young-Min Kim; Kangmo Ahn; Hywel C. Williams; Reiko J Tanaka

    Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 20% of children worldwide. Although environmental factors including weather and air pollutants have been shown to be associated with AD symptoms, the time-dependent nature of such a relationship has not been adequately investigated. Objective: This paper aims to assess the short-term impact of weather and air pollutants

  • A two-arm, randomized, controlled, multi-centric, open-label Phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19
    medRxiv. Allergy Immunol. Pub Date : 2020-12-02
    Suresh Kumar; Rosemarie de Souza; Milind Nadkar; Randeep Guleria; Anjan Trikha; Shashank R Joshi; Subramanian Loganathan; Sivakumar Vaidyanathan; Ashwani Marwah; Sandeep N Athalye

    An uncontrolled increase in cytokine production may lead to systemic hyperinflammation, vascular hypo-responsiveness, increased endothelial permeability, hypercoagulation, multi-organ dysfunction and eventually death in moderate to severely ill COVID-19 patients. Targeting T-cells, an important driver of the hyperinflammatory response, in the treatment of COVID-19, could potentially reduce mortality

  • CDH26 amplifies airway epithelial IL-4 receptor α signaling in asthma
    medRxiv. Allergy Immunol. Pub Date : 2020-12-02
    Yuchen Feng; Shengchong Chen; Chenli Chang; Wenliang Wu; Dian Chen; Jiali Gao; Gongqi Chen; Lingling Yi; Guohua Zhen

    Background: Activation of interleukin (IL)-4 receptor (R) signaling in airway epithelial cells leads to airway hyperresponsiveness and mucus overproduction in asthma. Cadherin-26 (CDH26), a cadherin implicated in polarization of airway epithelial cells, is upregulated in asthma. However, the role of CDH26 in asthma remains unknown. We hypothesize that CDH26 plays a role in airway epithelial IL-4R signaling

  • Cytokine ranking via mutual information algorithm correlates cytokine profiles with disease severity in patients with COVID-19
    medRxiv. Allergy Immunol. Pub Date : 2020-11-27
    Kelsey Huntington; Anna Louie; Chun Geun Lee; Jack A. Elias; Eric A. Ross; Wafik S. El-Deiry

    Although the range of immune responses to COVID-19 infection is variable, cytokine storm is observed in many affected individuals. Here we utilize a mutual information algorithm that classifies the information gain for COVID-19 Severity Score (CSS) prediction provided by cytokine expression levels and clinical variables. We found a small number of clinical and cytokine expression variables are predictive

  • BCG vaccine derived peptides induce SARS-CoV-2 T cell cross-reactivity
    medRxiv. Allergy Immunol. Pub Date : 2020-11-23
    Peter J Eggenhuizen; Boaz H Ng; Janet Chang; Ashleigh L Fell; Wey Y Wong; Poh-yi Gan; Stephen R Holdsworth; Joshua D Ooi

    Epidemiological studies suggest that the Bacillus Calmette-Guerin (BCG) vaccine may have protective effects against coronavirus disease 2019 (COVID-19); and, there are now more than 15 ongoing clinical trials seeking to determine if BCG vaccination can prevent or reduce the severity of COVID-19 (1). However, the mechanism by which BCG vaccination can induce a severe acute respiratory syndrome coronavirus

  • Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence
    medRxiv. Allergy Immunol. Pub Date : 2020-11-20
    Gemma E. Hartley; Emily S.J. Edwards; Pei M. Aui; Nirupama Varese; Stephanie Stojanovic; James McMahon; Anton Y. Peleg; Irene Boo; Heidi E. Drummer; P. Mark Hogarth; Robyn E. O'Hehir; Menno C. van Zelm

    Background: Lasting immunity to SARS-CoV-2 following infection is questioned because serum antibodies decline in convalescence. However, functional immunity is mediated by long-lived memory T and B (Bmem) cells. Objective: To determine the longevity and immunophenotype of SARS-CoV-2-specific Bmem cells in COVID-19 patients. Methods: Recombinant spike receptor binding domain (RBD) and nucleocapsid protein

  • Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response
    medRxiv. Allergy Immunol. Pub Date : 2020-11-16
    Adrian M Shields; Sian E Faustini; Marisol Perez-Toledo; Sian Jossi; Joel D Allen; Saly Al-Taei; Claire Backhouse; Lynsey Dunbar; Daniel Ebanks; Beena Emmanuel; Aduragbemi A Faniyi; Mark A Garvey; Annabel Grinbergs; Golaleh McGinnell; Joanne O'Neill; Yasunori Watanabe; Max Crispin; David C Wraith; Adam F Cunningham; Mark T Drayson; Alex G Richter

    Objective To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19. Design A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19. Setting University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT). Participants 956 health care workers were recruited by open invitation

  • SARS-CoV-2 antigens expressed in plants detect antibody responses in COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2020-11-13
    Mohau S Makatsa; Marius B Tincho; Jerome M Wendoh; Sherazaan D Ismail; Rofhiwa Nesamari; Francisco Pera; Scott de Beer; Anura David; Sarika Jugwanth; Maemu P Gededzha; Nakampe Mampeule; Ian Sanne; Wendy Stevens; Lesley Scott; Jonathan Blackburn; Elizabeth S Mayne; Roanne S Keeton; Wendy A Burgers

    Background: The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods, with over 16 million confirmed cases and at least 650 000 deaths from COVID-19 in the first 7 months of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived

  • Quantitative measurement of IgG to SARS-CoV-2 proteins using ImmunoCAP
    medRxiv. Allergy Immunol. Pub Date : 2020-11-12
    Behnam Keshavarz; Joesph R. Wiencek; Lisa J. Workman; Matthew D. Straesser; Lyndsey M. Muehling; Glenda Canderan; Fabrizio Drago; Catherine A. Bonham; Jeffrey M. Sturek; Chintan Ramani; Coleen A. McNamara; Judith A. Woodfolk; Alexandra Kadl; Thomas A.E. Platts-Mills; Jeffrey M. Wilson

    Background: Detailed understanding of the immune response to SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), has been hampered by a lack of quantitative antibody assays. Objective: To develop a quantitative assay for IgG to SARS-CoV-2 proteins that could readily be implemented in clinical and research laboratories. Methods: The biotin-streptavidin technique was used to conjugate SARS-CoV-2

  • Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2
    medRxiv. Allergy Immunol. Pub Date : 2020-11-06
    Peter Sieling; Lise Zakin; Annie Shin; Brett Morimoto; Helty Adisetiyo; Hermes Garban; Philip Liu; Adrian Rice; Justin Taft; Roosheel Patel; Sofija Buta; Marta Martin-Fernandez; Dusan Bogunovic; Elizabeth Gabitzsch; Jeffrey T. Safrit; Lennie Sender; Patricia Spilman; Shahrooz Rabizadeh; Kayvan Niazi; Patrick Soon-Shiong

    To address the need for a safe, efficacious vaccine against SARS-CoV-2 infection with the critical properties of enabling both blocking viral entry into cells and clearing virus from cells already infected, we have developed a bivalent, human adenovirus serotype 5 (hAd5) SARS-CoV-2 S-Fusion + N-ETSD vaccine that is currently in clinical testing. This vaccine uses the next-generation hAd5 [E1-, E2b-

  • Caspases in COVID-19 Disease and Sequela and the Therapeutic Potential of Caspase Inhibitors
    medRxiv. Allergy Immunol. Pub Date : 2020-11-04
    Matthew Plassmeyer; Oral Alpan; Michael Corley; Kimberleigh Lillard; Paige Coatney; Tina Vaziri; Suzan Michalski; Thomas A Premeaux; Alina P.S. Pang; Zaheer Bukhari; Stephen Y Yueng; Teresa Evering; Gail Naughton; Martin Latterich; Philip A Mudd; Alfred Spada; Nicole Rindone; Denise Loizou; Lishomwa Ndhlovu; Raavi Gupta

    At present, there are is no effective vaccine and only one FDA approved early-stage therapy against infection with the SARS-CoV-2 virus to prevent disease progression. The excessive inflammation and tissue damage associated with COVID-19 can lead to immediate (i.e. respiratory failure, sepsis, and ultimately, death) or long-term health problems (i.e. fatigue, dyspnea, cough, joint pain, anosmia) and

  • Maternal late-pregnancy serum unmetabolized folic acid concentrations are not associated with infant allergic disease - A prospective cohort study
    medRxiv. Allergy Immunol. Pub Date : 2020-11-03
    Karen Best; Tim J Green; Dian Sulistyoningrum; Thomas R Sullivan; Susanne Aufreiter; Susan Prescott; Maria Makrides; Monika Skubisz; Deborah L O'Connor; Debra J Palmer

    Background: The increase in childhood allergic disease in recent decades has coincided with increased folic acid intakes during pregnancy. Circulating unmetabolized folic acid (UMFA) has been proposed as a biomarker of excessive folic acid intake. Objective: We aimed to determine if late-pregnancy serum UMFA and total folate concentrations were associated with allergic disease risk in the offspring

  • Characterization of Mycobacterium tuberculosis-specific Th22 cells and the effect of tuberculosis disease and HIV co-infection
    medRxiv. Allergy Immunol. Pub Date : 2020-10-26
    Mohau S. Makatsa; F. Millicent A. Omondi; Rubina Bunjun; Robert J. Wilkinson; Catherine Riou; Wendy A. Burgers

    The development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4+ T cells producing IL-22, a distinct subset termed Th22 cells, may contribute to protective immunity to TB. Thus, we characterized Mycobacterium tuberculosis (Mtb)-specific Th22 (and Th1 and Th17) cells

  • BCG vaccination induces enhanced frequencies of memory T and B cells and dendritic cell subsets in elderly individuals
    medRxiv. Allergy Immunol. Pub Date : 2020-10-26
    Nathella Pavan Kumar; Chandrasekaran Padmapriyadarsini; Anuradha Rajamanickam; Perumal Kannabiran Bhavani; Arul Nancy; Bharathi Jayadeepa; Nandhini Selvaraj; Dinesh Kumar; Rachel Mariam Renji; Vijayalakshmi Venkataramani; Tripathy SP; Subash Babu

    Background: BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional innate and adaptive immune cells subsets is not well characterized. Methods: We investigated the impact of BCG vaccination on the frequencies of T cell, B cell, monocyte and dendritic cell subsets as well as total antibody

  • COVID-19 adaptive humoral immunity models: non-neutralizing versus antibody-disease enhancement scenarios
    medRxiv. Allergy Immunol. Pub Date : 2020-10-23
    Antoine Danchin; Oriane Pagani-Azizi; Gabriel Turinici; Ghozlane Yahiaoui

    The interplay between the virus, infected cells and the immune ressponses to SARS-CoV-2 is still under debate. Extending the basic model of viral dynamics we propose here a formal approach to describe the neutralizing versus non-neutralizing scenarios and compare with the possible effects of antibody-dependent enhancement (ADE). The theoretical model is consistent with data available from the literature

  • Percentage HScore confirms low incidence of secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2020-10-21
    Michael R Ardern-Jones; Matt Stammers; Hang T.T. Phan; Florina Borca; Anastasia Koutalopoulou; Ying Teo; James Batchelor; Trevor Smith; Andrew S Duncombe

    Objective: It has been assumed that a significant proportion of COVID-19 patients show evidence of hyperinflammation of which secondary haemophagocytic lymphohistiocytosis (sHLH) is the most severe manifestation. To facilitate diagnosis of sHLH the HScore has been developed and validated. We set out to examine the prevalence of sHLH-like hyperinflammation in COVID-19. Methods: We retrospectively examined

  • Prevalence and risk factors of chronic kidney disease in a populated area with highly moving populations
    medRxiv. Allergy Immunol. Pub Date : 2020-10-21
    Mohammad Khajedaluee; Sanaz Ahmadi Ghezeldasht; Arman Mosavat; Reza Hekmat; Seyed Abdolrahim Rezaee; Tahereh Hassannia

    Background:Chronic kidney disease (CKD) is a major public health problem worldwide. Prevalence and associated risk factors of CKD was evaluated in the greater Mashhad, a highly populated pilgrimage city, in 2018 on 2,976 subjects. Methods:This study was carried out in the greater Mashhad, a highly populated pilgrimage city, in 2018 on 2,976 subjects. For each participant a standard questionnaire, a

  • Novel SARS-CoV-2 specific antibody and neutralization assays reveal wide range of humoral immune response during COVID-19.
    medRxiv. Allergy Immunol. Pub Date : 2020-10-14
    Mikail Dogan,Lina Kozhaya,Lindsey Placek,Courtney Gunter,Mesut Yigit,Rachel Hardy,Matt Plassmeyer,Paige Coatney,Kimberleigh Lillard,Zaheer Bukhari,Michael Kleinberg,Chelsea Hayes,Moshe Arditi,Ellen Klapper,Noah Merin,Bruce T Liang,Raavi Gupta,Oral Alpan,Derya Unutmaz

    Development of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n=115) and were absent in the negative controls

  • Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave
    medRxiv. Allergy Immunol. Pub Date : 2020-10-14
    Catherine J. Reynolds; Leo Swadling; Joseph M. Gibbons; Corinna Pade; Melanie Jensen; Mariana O. Diniz; Nathalie M. Schmidt; David K. Butler; Oliver E. Amin; Sasha N. L. Bailey; Stephen Talyor; Jessica Jones; Meleri Jones; Wing Yiu Jason Lee; Joshua Rosenheim; Aneesh Chandran; George Joy; Cecilia Di Genova; Nigel J. Temperton; Jonathan Lambourne; Teresa Cutino-Moguel; Mervyn Andiapen; Marianna Fontana;

    Studies of adaptive immunity to SARS-CoV-2 include characterisation of lethal, severe and mild cases. Understanding how long immunity lasts in people who have had mild or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed to and infected by SARS-CoV-2 during the early stages of the pandemic are an invaluable resource to study this question. The UK COVIDsortium is a longitudinal

  • Sex Differences in the Impact of Childhood Socioeconomic Status on Immune Function
    medRxiv. Allergy Immunol. Pub Date : 2020-10-05
    Jeffrey Gassen; Jordon White; Julia Peterman; Summer Mengelkoch; Randi Proffit Leyva; Marjorie Prokosch; Micah Eimerbrink; Kelly Brice; Dennis Cheek; Gary Boehm; Sarah Hill

    We examined relationships between multiple sources of early life stress and adult immune function in humans. Adult participants provided retrospective information about their childhood a) socioeconomic status, b) household unpredictability, and c) exposure to adverse experiences. Peripheral blood mononuclear cells were then isolated for use in functional assays: a) tumor cell lysis by natural killer

  • Different innate and adaptive immune response to SARS-CoV-2 infection of asymptomatic, mild and severe cases
    medRxiv. Allergy Immunol. Pub Date : 2020-09-28
    Rita Carsetti; Salvatore Zaffina; Eva Piano Mortari; Sara Terreri; Francesco Corrente; Claudia Capponi; Patrizia Palomba; Mattia Mirabella; Simona Cascioli; Paolo Palange; Ilaria Cuccaro; Cinzia Milito; Alimuddin Zumla; Markus Maeurer; Vincenzo Camisa; Maria Rosaria Vinci; Annapaola Santoro; Eleonora Cimini; Luisa Marchioni; Emanuele Nicastri; Fabrizio Palmieri; Chiara Agrati; Giuseppe Ippolito; Ottavia

    SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focussed on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ

  • Predictors of Incident Viral Symptoms Ascertained in the Era of Covid-19
    medRxiv. Allergy Immunol. Pub Date : 2020-09-25
    Gregory Marcus; Jeffrey E Olgin; Noah Peyser; Eric Vittinghoff; Vivian Yang; Sean Joyce; Robert Avram; Geoffrey Tison; David Wen; Xochitl Butcher; Helena Eitel; Mark Pletcher

    Background: In the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission. Methods: We conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a

  • Microfluidic Affinity Profiling reveals a Broad Range of Target Affinities for Anti-SARS-CoV-2 Antibodies in Plasma of Covid Survivors
    medRxiv. Allergy Immunol. Pub Date : 2020-09-23
    Matthias M. Schneider; Marc Emmenegger; Catherine K. Xu; Itzel Condado Morales; Priscilla Turelli; Manuela R. Zimmermann; Beat M. Frey; Sebastian Fiedler; Viola Denninger; Georg Meisl; Vasilis Kosmoliaptsis; Heike Fiegler; Didier Trono; Tuomas P. J. Knowles; Adriano AA Aguzzi

    The clinical outcome of SARS-CoV-2 infections can range from asymptomatic to lethal, and is thought to be crucially shaped by the quality of the immune response which includes antibody titres and affinity for their targets. Using Microfluidic Antibody Affinity Profiling (MAAP), we determined the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive

  • Developing a machine learning environmental allergy prediction model from real world data through a novel decentralized mobile study platform.
    medRxiv. Allergy Immunol. Pub Date : 2020-09-23
    Chethan Sarabu; Sandra Steyaert; Nirav Shah

    Environmental allergies cause significant morbidity across a wide range of demographic groups. This morbidity could be mitigated through individualized predictive models capable of guiding personalized preventive measures. We developed a predictive model by integrating smartphone sensor data with symptom diaries maintained by patients. The machine learning model was found to be highly predictive, with

  • Pre-existing T cell memory as a risk factor for severe 1 COVID-19 in the elderly
    medRxiv. Allergy Immunol. Pub Date : 2020-09-18
    Petra Bacher; Elisa Rosati; Daniela Esser; Gabriela Rios Martini; Carina Saggau; Esther Schiminsky; Justina Dargvainiene; Ina Schröder; Imke Wieters; Fabian Eberhardt; Holger Neb; Yascha Khodamoradi; Michael Sonntagbauer; Maria JGT Vehreschild; Claudio Conrad; Florian Tran; Philip Rosenstiel; Robert Markewitz; Klaus-Peter Wandinger; Jan Rybniker; Matthias Kochanek; Frank Leypoldt; Oliver A Cornely;

    Coronavirus disease 2019 (COVID-19) displays high clinical variability but the parameters that determine disease severity are still unclear. Pre-existing T cell memory has been hypothesized as a protective mechanism but conclusive evidence is lacking. Here we demonstrate that all unexposed individuals harbor SARS-CoV-2-specific memory T cells with marginal cross-reactivity to common cold corona and

  • Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration.
    medRxiv. Allergy Immunol. Pub Date : 2020-09-16
    Krista L Newell,Deanna C Clemmer,Justin B Cox,Yetunde I Kayode,Victoria Zoccoli-Rodriguez,Harry E Taylor,Timothy P Endy,Joel R Wilmore,Gary Winslow

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral

  • Proteo-transcriptomic profiling of nasal mononuclear phagocytic system cells in human controlled allergen challenge
    medRxiv. Allergy Immunol. Pub Date : 2020-09-10
    Astrid L Voskamp; Maarten L Gerdes; Roberta Menafra; Ellen Duijster; Szymon M Kielbasa; Tom Groot Kormelink; Tamar Tak; Koen A Stam; Nicolette W de Jong; Rudi W Hendricks; Susan L Kloet; Maria Yazdanbakhsh; Esther C De Jong; Roy Gerth van Wijk; Hermelijn H Smits

    Immune homeostasis is essential to protect mucosal airway surfaces from unnecessary and damaging inflammation against inhaled harmless environmental antigens, such as allergens. However, in allergic individuals this protective homeostatic response seems absent. Innate cells part of the mononuclear phagocytic system (MPS) play an important role in these processes. Most of our knowledge on allergic immune

  • Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci
    medRxiv. Allergy Immunol. Pub Date : 2020-09-03
    Yun R. Li; Jin Li; Joseph T. Glessner; Jie Yang; Michael E. March; Charlly Kao; Jonathan P. Bradfield; Junyi Li; Frank D. Mentch; Huiqi Qu; Xiaohui Qi; Xiao Chang; Cuiping Hou; Debra J. Abrams; Haijun Qiu; Zhi Wei; John J. Connolly; Fengxiang Wang; James Snyder; Sophie Limou; Berit Flatø; Øystein Førr; Susan D. Thompson; Carl D. Langefeld; David N. Glass; Mara L. Becker; Elena Perez; Benedicte A. Lie;

    Juvenile Idiopathic Arthritis (JIA) is the most common type of arthritis among children, encompassing a highly heterogeneous group of immune-mediated joint disorders, being classified into seven subtypes based on clinical presentation. To systematically understand the distinct and shared genetic underpinnings of JIA subtypes, we conducted a heterogeneity-sensitive GWAS encompassing a total of 1245

  • Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2020-08-29
    Baweleta Isho; Kento T Abe; Michelle Zuo; Alainna J Jamal; Bhavisha Rathod; Jenny H Wang; Zhijie Li; Gary Chao; Olga L Rojas; Yeo Myong Bang; Annie Pu; Natasha Christie-Holmes; Christian Gervais; Derek Ceccarelli; Payman Samavarchi-Tehrani; Furkan Guvenc; Patrick Budylowski; Angel Li; Aimee Paterson; Yue Feng Yun; Lina M Marin; Lauren Caldwell; Jeffrey L Wrana; Karen Colwill; Frank Sicheri; Samira

    While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody

  • Development of antibodies to pan-coronavirus spike peptides in convalescent COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2020-08-22
    Andrii Rabets; Galyna Bila; Roman Grytsko; Markian Samborsky; Yuriy Rebets; Sandor Vari; Quentin Pagneux; Alexandre Barras; Rabah Boukherroub; Sabine Szunerits; Rostyslav Bilyy

    Coronaviruses are sharing several protein regions notable the spike protein (S) on their enveloped membrane surface, with the S1 subunit recognizing and binding to the cellular receptor, while the S2 subunit mediates viral and cellular membrane fusion. This similarity opens the question whether infection with one coronavirus will confer resistance to other coronaviruses? Investigating patient serum

  • Mechanisms and kinetics of bacterial clearance after experimental colonisation in adults with asthma
    medRxiv. Allergy Immunol. Pub Date : 2020-08-22
    Seher Raza Zaidi; Simon P Jochems; Jesus Reine; Sherin Pojar; Elissavet Nikolaou; Elena Mitsi; Esther L German; Angela D Hyder-Wright; Hugh Adler; Hellen Hill; Caroline Hales; Victoria Connor; Carla Solorzano Gonzalez; Stephen Gordon; John Blakey; David Goldblatt; Daniela Ferreira; Jamie Rylance

    Background Pneumococcal pneumonia is a leading cause of death, particularly affecting those with chronic respiratory disease. Observational studies suggest increased nasopharyngeal colonisation rates with S.pneumoniae in asthma, and lower specific antibody levels. Objectives Using experimental human pneumococcal challenge, we examined the acquisition and kinetics of nasopharyngeal colonisation of Streptococcus

  • Laboratory biomarkers associated with COVID-19 severity and management.
    medRxiv. Allergy Immunol. Pub Date : 2020-08-21
    Stephen Keddie; Oliver J Ziff; Michael KL Chou; Rachel L Taylor; Amanda Heslegrave; Edmund Garr; Neghat Lakdawala; Andrew Church; Dalia Ludwig; Jessica Manson; Marie Scully; Eleni Nastouli; Miles D Chapman; Melanie Hart; Michael P Lunn

    The heterogeneous disease course of COVID-19 is unpredictable, ranging from mild self-limiting symptoms to cytokine storms, acute respiratory distress syndrome (ARDS), multi-organ failure and death. Identification of high-risk cases will enable appropriate intervention and escalation. This study investigates the routine laboratory tests and cytokines implicated in COVID-19 for their potential application

  • The ImmuneRACE Study: A Prospective Multicohort Study of Immune Response Action to COVID-19 Events with the ImmuneCODE™ Open Access Database
    medRxiv. Allergy Immunol. Pub Date : 2020-08-21
    Jennifer N. Dines; Thomas J. Manley; Emily Svejnoha; Heidi M. Simmons; Ruth Taniguchi; Mark Klinger; Lance Baldo; Harlan Robins

    Background: Adaptive Biotechnologies has built an immune medicine platform based on the sequencing of immune receptors (immunoglobulins, B-cell receptors [BCRs] and T-cell receptors [TCRs]) with myriad applications in health and disease. This broad platform technology can be used to assess the diversity of the cellular adaptive immune system and track disease-associated TCRs and BCRs during the course

  • Complement C3 vs C5 inhibition in severe COVID-19: early clinical findings reveal differential biological efficacy
    medRxiv. Allergy Immunol. Pub Date : 2020-08-21
    Dimitrios C. Mastellos; Bruno G. P. Pires da Silva; Benedito A. L. Fonseca; Natasha P. Fonseca; Maria A. Martins; Sara Mastaglio; Annalisa Ruggeri; Marina Sironi; Peter Radermacher; Panagiotis Skendros; Konstantinos Ritis; Ilenia Manfra; Simona Iacobelli; Markus Huber-Lang; Bo Nilsson; Despina Yancopoulou; E. Sander Connolly; Cecilia Garlanda; Fabio Ciceri; Antonio M. Risitano; Rodrigo T. Calado; John

    Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel thrombotic microangiopathy and NET-driven immunothrombosis, thereby exacerbating cytokine-driven hyper-inflammation and multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2

  • Transcriptome-wide Association Study of Circulating IgE Levels Identifies Novel Targets for Asthma and Allergic Diseases
    medRxiv. Allergy Immunol. Pub Date : 2020-08-18
    Kathryn Recto; Tianxiao Huan; Dong Heon Lee; Gha Young Lee; Jessica Gereige; Chen Yao; Shih-Jen Hwang; Roby Joehanes; Rachel Kelly; George O'Connor; Jessica Lasky-Su; Daniel Levy

    Measurement of circulating immunoglobulin E (IgE) concentration is helpful for diagnosing and treating asthma and allergic diseases. Identifying gene expression signatures associated with IgE might elucidate novel pathways for IgE regulation. To this end, we performed a discovery transcriptome-wide association study (TWAS) to identify differentially expressed genes associated with circulating IgE levels

  • Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 patients
    medRxiv. Allergy Immunol. Pub Date : 2020-08-12
    Ling Ni; Meng-Li Cheng; Hui Zhao; Yu Feng; Jingyuan Liu; Fang Ye; Qing Ye; Gengzhen Zhu; Xiaoli Li; Pengzhi Wang; Jing Shao; Yong-qiang Deng; Peng Wei; Fang Chen; Cheng-feng Qin; Guoqing Wang; Fan Li; Hui Zeng; Chen Dong

    The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, the basis of which remains largely unclear. Currently, though convalescent individuals have been shown with both cellular and humoral immune responses, there is very limited understanding on the immune responses, especially adaptive immune