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1. Three doses of Sars-CoV-2 mRNA vaccine in older adults result in similar antibody responses but reduced cellular cytokine responses relative to younger adults

Author

Bredholt, Geir, Sævik, Marianne, Søyland, Hanne, Ueland, Thor, Zhou, Fan, Pathirana, Rishi, Madsen, Anders, Vahokoski, Juha, Lartey, Sarah, Halvorsen, Bente E., Dahl, Tuva B., Trieu, Mai-Chi, Mohn, Kristin G.-I., Brokstad, Karl Albert, Aukrust, Pål, Tøndel, Camilla, Langeland, Nina, Blomberg, Bjørn, and Cox, Rebecca Jane

Published
2024
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2. A rapid antibody screening haemagglutination test for predicting immunity to SARS-CoV-2 variants of concern

Author

Ertesvåg, Nina Urke, Xiao, Julie, Zhou, Fan, Ljostveit, Sonja, Sandnes, Helene, Lartey, Sarah, Sævik, Marianne, Hansen, Lena, Madsen, Anders, Mohn, Kristin G. I., Fjelltveit, Elisabeth, Olofsson, Jan Stefan, Tan, Tiong Kit, Rijal, Pramila, Schimanski, Lisa, Øyen, Siri, Brokstad, Karl Albert, Dunachie, Susanna, Jämsén, Anni, James, William S., Harding, Adam C., Harvala, Heli, Nguyen, Dung, Roberts, David, Zambon, Maria, Townsend, Alain, Langeland, Nina, and Cox, Rebecca Jane

Published
2022
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4. Long COVID in a prospective cohort of home-isolated patients

Author

Blomberg, Bjørn, Mohn, Kristin Greve-Isdahl, Brokstad, Karl Albert, Zhou, Fan, Linchausen, Dagrun Waag, Hansen, Bent-Are, and Lartey, Sarah

Subjects
Isolation (Hospital care) -- Health aspects -- Demographic aspects, Biological sciences, Health
Abstract

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients--247 home-isolated and 65 hospitalized--comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16-30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination. Analysis of a prospectively enrolled cohort of patients with SARS-CoV-2 infections in Bergen, Norway, reveals a high proportion of patients who experienced long COVID symptoms at 6 months, despite being relatively young and having only mild to moderate acute COVID-19 symptoms., Author(s): Bjørn Blomberg [sup.1] [sup.2] [sup.3] , Kristin Greve-Isdahl Mohn [sup.3] [sup.4] , Karl Albert Brokstad [sup.5] [sup.6] , Fan Zhou [sup.4] , Dagrun Waag Linchausen [sup.7] , Bent-Are Hansen [...]

Published
2021
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5. Impact of Pre-Existing Immunity and Age on Antibody Responses to Live Attenuated Influenza Vaccine.

Author

Hoen, Lukas, Lartey, Sarah, Zhou, Fan, Pathirana, Rishi D., Krammer, Florian, Mohn, Kristin G -I, Cox, Rebecca J., and Brokstad, Karl A.

Subjects
ANTIBODY formation, INFLUENZA vaccines, IMMUNE response, IMMUNE system, HEMAGGLUTININ
Abstract

Live attenuated influenza vaccines (LAIV) typically induce a poor hemagglutination inhibition (HI) response, which is the standard correlate of protection for inactivated influenza vaccines. The significance of the HI response is complicated because the LAIV vaccine primarily induces the local mucosal immune system, while the HI assay measures the circulating serum antibody response. However, age and pre-existing immunity have been identified as important factors affecting LAIV immunogenicity. This study aimed to extend our understanding of LAIV-induced immunity, particularly, the impact age and pre-existing immunity have on eliciting functional and neutralising antibody responses in paediatric and adult populations vaccinated with LAIV. Thirty-one children and 26 adults were immunized with the trivalent LAIV during the 2013–2014 influenza season in Norway. Children under 9 years received a second dose of LAIV 28 days after the first dose. Blood samples were collected pre- and post-vaccination. HI, microneutralization (MN) and enzyme-linked lectin assay for neuraminidase (NA) antibodies were measured against the vaccine strains. IgG antibody avidity against hemagglutinin (HA) and NA proteins from the vaccine strains was also assessed. Significant correlations were observed between HI and MN responses to A/California/7/2009 (A/H1N1)pdm09-like strain and B/Massachusetts/2/2012-like strain, suggesting that MN is a potential immunological correlate for LAIV. However, the relationship between recipient age (or priming status) and serological response varied between vaccine strains. There was a notable increase in HI and MN responses in all cohorts except naive children against the H1N1 strain, where most recipients had responses below the protective antibody threshold. NAI responses were generally weak in naive children against all vaccine strains compared with adults or antigen-primed children. Post-vaccination antibody avidity increased only in primed children below nine years of age against the A/H1N1 strain. Overall, our findings indicate that LAIV elicits functional and neutralizing antibody responses in both naive and antigen experienced cohorts, however, the magnitude and kinetics of the response varies between vaccine strains. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Impact of ageing on homologous and human-coronavirus-reactive antibodies after SARS-CoV-2 vaccination or infection.

Author

Zhou, Fan, Vahokoski, Juha, Bergen COVID-19 Research Group, Øyen, Siri, Sævik, Marianne, Høyland, Hanne, Sandnes, Helene H., Madsen, Anders, Brokstad, Karl A., Mohn, Kristin G. I., Tøndel, Camilla, Langeland, Nina, and Cox, Rebecca J.

Subjects
SARS-CoV-2, COVID-19, IMMUNOGLOBULINS, ANTIBODY formation, VACCINATION, VIRAL antibodies, MONOCLONAL antibodies
Abstract

The endemic human coronaviruses (HCoVs) circulate worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses and the boosting of HCoV-reactive antibodies after SARS-CoV-2 vaccination or infection in individuals up to 98 years old. All the vaccinees were home-dwelling with no documented SARS-CoV-2 infection before receiving the COVID-19 mRNA vaccine (BNT162b2). The first two vaccine doses elicited potent SARS-CoV-2 spike binding antibodies in individuals up to 80 years. The third dose largely boosted the previously low S2 domain binding and neutralizing antibodies in elderly 80–90 years old, but less so in those above 90 years. The endemic betacoronavirus (HKU1 and OC43) reactive antibodies were boosted in all vaccinees, although to a lesser extent in those above 80 years old. COVID-19 patients had potent elevation of alpha- and betacoronavirus (229E, NL63, HKU1 and OC43) reactive antibodies. In both patients and vaccinees, S2 domain specific antibody increases correlated with SARS-CoV-2 neutralizing and HCoV-reactive antibody responses in all ages, indicating S2 domain as a candidate for future universal coronavirus vaccine design. [ABSTRACT FROM AUTHOR]

Published
2024
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13. Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

Author

Hansen, Lena, primary, Brokstad, Karl Albert, additional, Bansal, Amit, additional, Zhou, Fan, additional, Bredholt, Geir, additional, Onyango, Therese Bredholt, additional, Sandnes, Helene Heitmann, additional, Elyanow, Rebecca, additional, Madsen, Anders, additional, Trieu, Mai-Chi, additional, Sævik, Marianne, additional, Søyland, Hanne, additional, Olofsson, Jan Stefan, additional, Vahokoski, Juha, additional, Ertesvåg, Nina Urke, additional, Fjelltveit, Elisabeth Berg, additional, Shafiani, Shahin, additional, Tøndel, Camilla, additional, Chapman, Heidi, additional, Kaplan, Ian, additional, Mohn, Kristin G.I., additional, Langeland, Nina, additional, and Cox, Rebecca Jane, additional

Published
2023
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17. SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients.

Author

Bredholt Onyango, Therese, Fan Zhou, Bredholt, Geir, Brokstad, Karl A., Lartey, Sarah, Mohn, Kristin G.-I., Özgümüs, Türküler, Kittang, Bård Reiakvam, Linchausen, Dagrun Waag, Shafiani, Shahin, Elyanow, Rebecca, Blomberg, Bjørn, Langeland, Nina, and Cox, Rebecca Jane

Subjects
COVID-19, COMPULSIVE eating, IMMUNE response, SARS-CoV-2, T cell receptors, OBESITY
Abstract

Obesity is a known risk factor for severe respiratory tract infections. In this prospective study, we assessed the impact of being obese or overweight on longitudinal SARS-CoV-2 humoral and cellular responses up to 18 months after infection. 274 patients provided blood samples at regular time intervals up to 18 months including obese (BMI ≥30, n=32), overweight (BMI 25-29.9, n=103) and normal body weight (BMI 18.5-24.9, n=134) SARS-CoV-2 patients. We determined SARS-CoV-2 spike-specific IgG, IgA, IgM levels by ELISA and neutralising antibody titres by neutralisation assay. RBD- and spike-specific memory B cells were investigated by ELISpot, spike- and non-spike-specific IFN-g, IL-2 and IFN-g/IL-2 secreting T cells by FluoroSpot and T cell receptor (TCR) sequencing was performed. Higher BMI correlated with increased COVID-19 severity. Humoral and cellular responses were stronger in overweight and obese patients than normal weight patients and associated with higher spike-specific IgG binding titres relative to neutralising antibody titres. Linear regression models demonstrated that BMI, age and COVID-19 severity correlated independently with higher SARS-CoV-2 immune responses. We found an increased proportion of unique SARS-CoV-2 specific T cell clonotypes after infection in overweight and obese patients. COVID-19 vaccination boosted humoral and cellular responses irrespective of BMI, although stronger immune boosting was observed in normal weight patients. Overall, our results highlight more severe disease and an overreactivity of the immune system in overweight and obese patients after SARSCoV-2 infection, underscoring the importance of recognizing overweight/obese individuals as a risk group for prioritisation for COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Supplementary Data 2 from Generation of Prostate Tumor–Initiating Cells Is Associated with Elevation of Reactive Oxygen Species and IL-6/STAT3 Signaling

Author

Qu, Yi, primary, Oyan, Anne Margrete, primary, Liu, Runhui, primary, Hua, Yaping, primary, Zhang, Jigang, primary, Hovland, Randi, primary, Popa, Mihaela, primary, Liu, Xiaojun, primary, Brokstad, Karl A., primary, Simon, Ronald, primary, Molven, Anders, primary, Lin, Biaoyang, primary, Zhang, Wei-dong, primary, McCormack, Emmet, primary, Kalland, Karl-Henning, primary, and Ke, Xi-Song, primary

Published
2023
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19. Data from Generation of Prostate Tumor–Initiating Cells Is Associated with Elevation of Reactive Oxygen Species and IL-6/STAT3 Signaling

Author

Qu, Yi, primary, Oyan, Anne Margrete, primary, Liu, Runhui, primary, Hua, Yaping, primary, Zhang, Jigang, primary, Hovland, Randi, primary, Popa, Mihaela, primary, Liu, Xiaojun, primary, Brokstad, Karl A., primary, Simon, Ronald, primary, Molven, Anders, primary, Lin, Biaoyang, primary, Zhang, Wei-dong, primary, McCormack, Emmet, primary, Kalland, Karl-Henning, primary, and Ke, Xi-Song, primary

Published
2023
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20. Supplementary Materials and Methods, Figure Legends, Figures 1-2, and Tables 1-2 from Generation of Prostate Tumor–Initiating Cells Is Associated with Elevation of Reactive Oxygen Species and IL-6/STAT3 Signaling

Author

Qu, Yi, primary, Oyan, Anne Margrete, primary, Liu, Runhui, primary, Hua, Yaping, primary, Zhang, Jigang, primary, Hovland, Randi, primary, Popa, Mihaela, primary, Liu, Xiaojun, primary, Brokstad, Karl A., primary, Simon, Ronald, primary, Molven, Anders, primary, Lin, Biaoyang, primary, Zhang, Wei-dong, primary, McCormack, Emmet, primary, Kalland, Karl-Henning, primary, and Ke, Xi-Song, primary

Published
2023
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24. Persistent Fever and Positive PCR 90 Days Post-SARS-CoV-2 Infection in a Rituximab-Treated Patient: A Case of Late Antiviral Treatment

Author

Ertesvåg, Nina Urke, primary, Sakkestad, Sunniva Todnem, additional, Zhou, Fan, additional, Hoff, Ingrid, additional, Kristiansen, Trygve, additional, Jonassen, Trygve Müller, additional, Follesø, Elisabeth, additional, Brokstad, Karl Albert, additional, Dyrhovden, Ruben, additional, and Mohn, Kristin G.-I., additional

Published
2022
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25. Variability of Primary Sjögren's Syndrome Is Driven by Interferon α and Interferon α Blood Levels Are Associated With the Class II HLA–DQ Locus

Author

Trutschel, Diana, Bost, Pierre, Mariette, Xavier, Bondet, Vincent, Llibre, Alba, Posseme, Celine, Charbit, Bruno, Thorball, Christian W., Jonsson, Roland, Lessard, Christopher J., Felten, Renaud, Ng, Wan Fai, Chatenoud, Lucienne, Dumortier, Hélène, Sibilia, Jean, Fellay, Jacques, Brokstad, Karl A., Appel, Silke, Tarn, Jessica R., Quintana‐Murci, Lluis, Mingueneau, Michael, Meyer, Nicolas, Duffy, Darragh, Schwikowski, Benno, Gottenberg, Jacques Eric, Dernis, Emmanuelle, Devauchelle‐Pensec, Valerie, Dieude, Philippe, Dubost, Jean‐Jacques, Fauchais, Anne‐Laure, Goeb, Vincent, Hachulla, Eric, Hatron, Pierre Yves, Larroche, Claire, Le Guern, Véronique, Morel, Jacques, Perdriger, Aleth, Salliot, Carinne, Rist, Stephanie, Saraux, Alain, Vittecoq, Olivier, Nocturne, Gaétane, Ravaud, Philippe, Seror, Raphaèle, Abel, Laurent, Alcover, Andres, Aschard, Hugues, Astrom, Kalla, Bousso, Philippe, Bruhns, Pierre, Cumano, Ana, Demangel, Caroline, Deriano, Ludovic, Di Santo, James, Dromer, Françoise, Eberl, Gérard, Enninga, Jost, Gelpi, Odile, GompertsBoneca, Ivo, Hasan, Milena, Hercberg, Serge, Lantz, Olivier, Leclerc, Claude, Mouquet, Hugo, Pellegrini, Sandra, Pol, Stanislas, Rausell, Antonio, Rogge, Lars, Sakuntabhai, Anavaj, Schwartz, Olivier, Shorte, Spencer, Soumelis, Vassili, Tangy, Frédéric, Tartour, Eric, Toubert, Antoine, Touvier, Mathilde, Ungeheuer, Marie‐Noëlle, Albert, Matthew L., Biomédecine computationelle des systèmes / Computational systems biomedicine, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Projet NECESSITY (PN), Hôpitaux Universitaires Paris Sud [AP-HP] (HUPS)-Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie Translationnelle - Translational Immunology lab, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Ecole Polytechnique Fédérale de Lausanne (EPFL), Université de Lausanne = University of Lausanne (UNIL), Lausanne University Hospital, University of Bergen (UiB), Oklahoma Medical Research Foundation (OMRF), University of Oklahoma Health Sciences Center (OUHSC), Université de Strasbourg (UNISTRA), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie, Immunopathologie et Chimie Thérapeutique (I2CT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biogen Inc. [Cambridge, MA, USA], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (grant 806975). The JU receives support from the European Union’s Horizon 2020 research and innovation program and the European Unionand the European Federation of Pharmaceutical Industries and Associations. This work was also supported by the National Institutes of Health (National Institute of Arthritis and Musculoskeletal Skin Disease grant R01-AR-065953). The Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome(ASSESS) national multicenter prospective cohort was formed in 2006 with aFrench Ministry of Health grant (Programme Hospitalier de Recherche Clinique 2005 P060228). The ASSESS cohort is promoted by the French Society of Rheumatology and receives research grants from the French Society of Rheumatology. Dr. Gottenberg’s work was supported by Bristol Myers Squibbfor transcriptomic analysis of the ASSESS and Norwegian cohorts and by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögrenet des syndromes secs). Drs. Trutschel’s and Schwikowski’s work was supported by Geneviève Garnier (Association Française du Syndrome de Gougerot-Sjögren et des syndromes secs)., Milieu Intérieur Consortium, ASSESS study investigators, and NECESSITY Consortium: Emmanuelle Dernis, Valerie Devauchelle-Pensec, Philippe Dieude, Jean-Jacques Dubost, Anne-Laure Fauchais, Vincent Goeb, Eric Hachulla, Pierre Yves Hatron, Claire Larroche, Véronique Le Guern, Jacques Morel, Aleth Perdriger, Carinne Salliot, Stephanie Rist, Alain Saraux, Jean Sibilia, Olivier Vittecoq, Gaétane Nocturne, Philippe Ravaud, Raphaèle Seror, Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Odile Gelpi, Ivo GompertsBoneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Eric Tartour, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci., European Project: 806975,NECESSITY, Clauss, Isabelle, and NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients - NECESSITY - 0000-00-00 - 0000-00-00 - 806975 - VALID

Subjects
Proteomics, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's Syndrome, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, HLA-DQ Antigens, Immunology, Humans, Interferon-alpha, Immunology and Allergy, Prospective Studies
Abstract

Objective: Primary Sjögren's syndrome (SS) is the second most frequent systemic autoimmune disease, affecting 0.1% of the general population. To characterize the molecular and clinical variabilities among patients with primary SS, we integrated transcriptomic, proteomic, cellular, and genetic data with clinical phenotypes in a cohort of 351 patients with primary SS. Methods: We analyzed blood transcriptomes and genotypes of 351 patients with primary SS who were participants in a multicenter prospective clinical cohort. We replicated the transcriptome analysis in 3 independent cohorts (n = 462 patients). We determined circulating interferon-α (IFNα) and IFNγ protein concentrations using digital single molecular arrays (Simoa). Results: Transcriptome analysis of the prospective cohort showed a strong IFN gene signature in more than half of the patients; this finding was replicated in the 3 independent cohorts. Because gene expression analysis did not discriminate between type I IFN and type II IFN, we used Simoa to demonstrate that the IFN transcriptomic signature was driven by circulating IFNα and not by IFNγ protein levels. IFNα protein levels, detectable in 75% of patients, were significantly associated with clinical and immunologic features of primary SS disease activity at enrollment and with increased frequency of systemic complications over the 5-year follow-up. Genetic analysis revealed a significant association between IFNα protein levels, a major histocompatibility (MHC) class II haplotype, and anti-SSA antibody. Additional cellular analysis revealed that an MHC class II HLA–DQ locus acts through up-regulation of HLA class II molecules on conventional dendritic cells. Conclusion: We identified the predominance of IFNα as a driver of primary SS variability, with IFNα demonstrating an association with HLA gene polymorphisms., Arthritis & Rheumatology, 74 (12), ISSN:2326-5191, ISSN:2326-5205

Published
2022
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27. H1N1 vaccination in Sjögren’s syndrome triggers polyclonal B cell activation and promotes autoantibody production

Author

Brauner, Susanna, Folkersen, Lasse, Kvarnström, Marika, Meisgen, Sabrina, Petersen, Sven, Franzén-Malmros, Michaela, Mofors, Johannes, Brokstad, Karl A, Klareskog, Lars, Jonsson, Roland, Westerberg, Lisa S, Trollmo, Christina, Malmström, Vivianne, Ambrosi, Aurelie, Kuchroo, Vijay K, Nordmark, Gunnel, and Wahren-Herlenius, Marie

Published
2017
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29. SARS-CoV-2–Specific Neutralizing Antibody Responses in Norwegian Health Care Workers After the First Wave of COVID-19 Pandemic: A Prospective Cohort Study

Author

Trieu, Mai-Chi, Bansal, Amit, Madsen, Anders, Zhou, Fan, Sævik, Marianne, Vahokoski, Juha, Brokstad, Karl Albert, Krammer, Florian, Tøndel, Camilla, Mohn, Kristin G I, Blomberg, Bjørn, Langeland, Nina, Cox, Rebecca J, Kittang, Bård, Linchausen, Dagrunn Waag, Amdam, Håkon, Onyango, Therese Bredholt, Bredholt, Geir, Ertesvåg, Nina, Lartey, Sarah, Sandnes, Helene Heitmann, Grøvan, Fredrik, Bartsch, Hauke, Syre, Heidi, Real, Francisco, and Berg, Åse Garløv

Subjects
Male, 0301 basic medicine, Immunoglobulin A, Antibodies, Viral, spike protein, Immunoglobulin G, 0302 clinical medicine, Pandemic, Immunology and Allergy, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Neutralizing antibody, Asymptomatic Infections, biology, Norway, neutralizing antibody, Middle Aged, 3. Good health, AcademicSubjects/MED00290, Infectious Diseases, Spike Glycoprotein, Coronavirus, Female, Antibody, IgA, Adult, IgM, IgG, Health Personnel, education, 030106 microbiology, health care workers, Young Adult, 03 medical and health sciences, Major Article, Humans, Seroconversion, seroconversion, Pandemics, Aged, antibody characterization, SARS-CoV-2, business.industry, COVID-19, Antibodies, Neutralizing, Immunoglobulin M, Immunology, biology.protein, business
Abstract

Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in health care workers (HCW) due to overburdened health care systems. Whether infected HCW acquire protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Methods In a Norwegian prospective cohort study, we enrolled 607 HCW before and after the first COVID-19 wave. Exposure history, COVID-19–like symptoms, and serum samples were collected. SARS-CoV-2–specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. Results Spike-specific IgG/IgM/IgA antibodies increased after the first wave in HCW with, but not in HCW without, COVID-19 patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse transcriptase polymerase chain reaction (RT-PCR) during follow-up; 8 were positive (7 seroconverted, 1 had undetectable antibodies). Conclusions We found increases in SARS-CoV-2 neutralizing antibodies in infected HCW, especially after COVID-19 patient exposure. Our data show a low number of SARS-CoV-2–seropositive HCW in a low-prevalence setting; however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing., Low numbers of SARS-CoV-2–seropositive HCW were found in Norway and 1.8% of HCW seroconverted with neutralizing antibodies. Seropositivity was higher than RT-PCR positivity in HCW with 36% asymptomatic, representing a risk of infection within the health care setting.

Published
2020
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30. Symptom burden and immune dynamics 6 to 18 months following mild SARS-CoV-2 infection -a case-control study

Author

Fjelltveit, Elisabeth Berg, Blomberg, Bjørn, Kuwelker, Kanika, Zhou, Fan, Onyango, Therese Bredholt, Brokstad, Karl Albert, Elyanow, Rebecca G, Kaplan, Ian, Tøndel, Camilla, Mohn, Kristin Greve-Isdahl, Özgümüs, Türküler, Cox, Rebecca Jane, and Langeland, Nina

Abstract

Background The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID. Methods A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses. Results Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27–10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51–15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88–20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22–5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5–21.5; P = .024) and among women (excess risk 18.7%; 95% CI, 4.4–32.9; P = .010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor β depth was significantly associated with both dyspnea and number of symptoms at 12 months. Conclusions This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms. publishedVersion

Published
2022

31. Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study.

Author

Fjelltveit, Elisabeth B, Blomberg, Bjørn, Kuwelker, Kanika, Zhou, Fan, Onyango, Therese B, Brokstad, Karl A, Elyanow, Rebecca, Kaplan, Ian M, Tøndel, Camilla, Mohn, Kristin G I, Özgümüş, Türküler, Cox, Rebecca J, Langeland, Nina, and Group, Bergen COVID-19 Research

Subjects
COVID-19, CONFIDENCE intervals, IMMUNOGLOBULINS, POST-acute COVID-19 syndrome, AGE distribution, TIME, CASE-control method, DYSPNEA, SYMPTOMS, ATTENTION, MEMORY disorders, RESEARCH funding, FATIGUE (Physiology), ODDS ratio, PSYCHOLOGICAL distress, LONGITUDINAL method
Abstract

Background The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID. Methods A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses. Results Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27–10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51–15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88–20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22–5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5–21.5; P =.024) and among women (excess risk 18.7%; 95% CI, 4.4–32.9; P =.010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor β depth was significantly associated with both dyspnea and number of symptoms at 12 months. Conclusions This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms. [ABSTRACT FROM AUTHOR]

Published
2023
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33. 21-Hydroxylase-Specific CD8+ T Cells in Autoimmune Addison’s Disease Are Restricted by HLA-A2 and HLA-C7 Molecules

Author

Hellesen, Alexander, primary, Aslaksen, Sigrid, additional, Breivik, Lars, additional, Røyrvik, Ellen Christine, additional, Bruserud, Øyvind, additional, Edvardsen, Kine, additional, Brokstad, Karl Albert, additional, Wolff, Anette Susanne Bøe, additional, Husebye, Eystein Sverre, additional, and Bratland, Eirik, additional

Published
2021
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35. Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome

Author

Thorlacius, Guðný Ella, Hultin-Rosenberg, Lina, Sandling, Johanna K., Bianchi, Matteo, Imgenberg-Kreuz, Juliana, Pucholt, Pascal, Theander, Elke, Kvarnström, Marika, Forsblad-D'elia, Helena, Bucher, Sara Magnusson, Norheim, Katrine B., Johnsen, Svein Joar Auglænd, Hammenfors, Daniel, Skarstein, Kathrine, Jonsson, Malin V., Baecklund, Eva, Aqrawi, Lara A., Jensen, Janicke Liaaen, Palm, Øyvind, Morris, Andrew P., Alexsson, Andrei, Backlin, Carin, Rönnblom, Lars, Vasaitis, Lilian, Eloranta, Maija Leena, Syvänen, Ann Christine, Mathioudaki, Argyri, Farias, Fabiana H.G., Meadows, Jennifer, Nordin, Jessika, Lindblad-Toh, Kerstin, Björk, Albin, Lundberg, Ingrid E., Sepúlveda, Jorge I.Ramírez, Wahren-Herlenius, Marie, Eriksson, Daniel, Eriksson, Per, Sjöwall, Christopher, Mandl, Thomas, Rantapaä¨-Dahlqvist, Solbritt, Brokstad, Karl A., Jonsson, Roland, Appel, Silke, Brun, Johan G., Norheim, Katrine Brække, Omdal, Roald, Aqrawi, Lara Adnan, Pielberg, Gerli Rosengren, Murén, Eva, Karlsson, Åsa, Andersson, Göran, Ahlgren, Kerstin M., Lobell, Anna, Söderkvist, Peter, Kämpe, Olle, Landegren, Nils, Meadows, Jennifer R.S., Lind, Lars, and Nordmark, Gunnel

Subjects
musculoskeletal diseases, stomatognathic diseases, stomatognathic system, gene polymorphism, autoantibodies, autoimmunity, Sjögren's syndrome, eye diseases
Abstract

Objectives: Clinical presentation of primary Sjögren's syndrome (pSS) varies considerably. A shortage of evidence-based objective markers hinders efficient drug development and most clinical trials have failed to reach primary endpoints. Methods: We performed a multicentre study to identify patient subgroups based on clinical, immunological and genetic features. Targeted DNA sequencing of 1853 autoimmune-related loci was performed. After quality control, 918 patients with pSS, 1264 controls and 107 045 single nucleotide variants remained for analysis. Replication was performed in 177 patients with pSS and 7672 controls. Results: We found strong signals of association with pSS in the HLA region. Principal component analysis of clinical data distinguished two patient subgroups defined by the presence of SSA/SSB antibodies. We observed an unprecedented high risk of pSS for an association in the HLA-DQA1 locus of odds ratio 6.10 (95% CI: 4.93, 7.54, P=2.2×10-62) in the SSA/SSB-positive subgroup, while absent in the antibody negative group. Three independent signals within the MHC were observed. The two most significant variants in MHC class I and II respectively, identified patients with a higher risk of hypergammaglobulinaemia, leukopenia, anaemia, purpura, major salivary gland swelling and lymphadenopathy. Replication confirmed the association with both MHC class I and II signals confined to SSA/SSB antibody positive pSS. Conclusion: Two subgroups of patients with pSS with distinct clinical manifestations can be defined by the presence or absence of SSA/SSB antibodies and genetic markers in the HLA locus. These subgroups should be considered in clinical follow-up, drug development and trial outcomes, for the benefit of both subgroups.

Published
2021
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37. Attack rates amongst household members of outpatients with confirmed COVID-19 in Bergen, Norway: A case-ascertained study

Author

Kuwelker, Kanika, primary, Zhou, Fan, additional, Blomberg, Bjørn, additional, Lartey, Sarah, additional, Brokstad, Karl Albert, additional, Trieu, Mai Chi, additional, Bansal, Amit, additional, Madsen, Anders, additional, Krammer, Florian, additional, Mohn, Kristin GI, additional, Tøndel, Camilla, additional, Linchausen, Dagrunn Waag, additional, Cox, Rebecca J., additional, Langeland, Nina, additional, Corydon, Annette, additional, Real, Francisco, additional, Bredholt, Geir, additional, Bartsch, Hauke, additional, Sandnes, Helene Heitmann, additional, Vahokoski, Juha, additional, Jacobsen, Kjerstin, additional, Eidsheim, Marianne, additional, Sævik, Marianne, additional, Ertesvåg, Nina Urke, additional, Hauge, Synnøve Ygre, additional, and Onyango, Therese Bredholt, additional

Published
2021
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39. Seroconversion in household members of COVID-19 outpatients

Author

Cox, Rebecca J, primary, Brokstad, Karl A, additional, Krammer, Florian, additional, Langeland, Nina, additional, Blomberg, Bjørn, additional, Kuwelker, Kanika, additional, Lartey, Sarah, additional, Linchausen, Dagrun Waag, additional, Mohn, Kristin GI, additional, Real, Francisco Gomez, additional, Bansal, Amit, additional, Bredholt, Geir, additional, Madsen, Anders, additional, Onanygo, Therese Bredholt, additional, Trieu, Mai Chi, additional, Vahokoski, Juha, additional, and Zhou, Fan, additional

Published
2021
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48. High attack rates of SARS-CoV-2 infection through household-transmission: a prospective study

Author

Kuwelker, Kanika, primary, Zhou, Fan, additional, Blomberg, Bjørn, additional, Lartey, Sarah, additional, Brokstad, Karl Albert, additional, Trieu, Mai Chi, additional, Madsen, Anders, additional, Krammer, Florian, additional, Mohn, Kristin GI, additional, Tøndel, Camilla, additional, Linchausen, Dagrunn Waag, additional, Cox, Rebecca J., additional, Langeland, Nina, additional, Bansal, Amit, additional, Corydon, Annette, additional, Real, Francisco, additional, Bredholt, Geir, additional, Bartsch, Hauke, additional, Sandnes, Helene Heitmann, additional, Vahokoski, Juha, additional, Jacobsen, Kjerstin, additional, Eidsheim, Marianne, additional, Sævik, Marianne, additional, Ertesvåg, Nina Urke, additional, Hauge, Synnøve Ygre, additional, and Onyango, Therese Bredholt, additional

Published
2020
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