Fridtjof Lund-Johansen

• Douvlataniotis, Dimitrios Karolos; Titov, Aleksei; Zeun, Julia; Bilici, Merve; Palashati, Heyilimu & Loh, Waywen [Show all 23 contributors for this article] (2026). TCR T cells targeting IgA- and IgG-expressing multiple myeloma∗. Blood. ISSN 0006-4971. doi: 10.1182/blood.2025031897. Full text in Research Archive Show summary

  T cell-based therapies have shown remarkable efficacy in multiple myeloma (MM), yet the disease remains largely incurable. Here, we investigated the constant domains of the immunoglobulin heavy chain (IgH) as novel targets for therapeutic T cell receptors (TCRs), after confirming high and homogeneous IGH expression in >95% of MM patients. MM cells secrete excessive monoclonal immunoglobulins (M-proteins) that drive complications but are inaccessible to CAR T-cell or antibody targeting. Peptides from IgA and IgG constant regions were eluted from HLA-A*02:01, and reactive TCRs were isolated from healthy donors using allo-HLA-A*02:01 presentation to circumvent self-tolerance. T cells engineered with two TCRs specific for IgA or IgG passed a stringent multi-tier safety screen and selectively eliminated MM cells from 20 HLA-A*02:01+ patients secreting the relevant IgH in vitro. In vivo, IgA-TCR T cells eradicated IgA+HLA-A*02:01+ MM cells in xenograft models and reduced circulating IgA in humanized mice. These findings establish immunoglobulin constant domains as viable TCR targets in MM, potentially making ~40% of patients of European descent eligible for TCR T cell therapy, and extension to additional HLA alleles could further broaden eligibility. The approach may also be applicable to lymphoma and antibody-mediated autoimmune diseases.

• Rasmussen, Tilde Harridsleff; Schikora-Rustad, Stine; Lorentzen, Åslaug Rudjord; Tran, Trung; Øverås, Mathias Herstad & Myhr, Kjell-Morten [Show all 22 contributors for this article] (2026). Low risk of severe COVID-19 in vaccinated people with multiple sclerosis: a nationwide Norwegian study. BMJ Neurology Open. 8(1). doi: 10.1136/bmjno-2026-001556. Full text in Research Archive Show summary

  Background: We aimed to assess antibody responses and COVID-19 outcomes after vaccination in people with multiple sclerosis (pwMS) receiving disease-modifying therapies. Methods: NevroVAX is a Norwegian multicentre cohort study including 3559 pwMS and 449 healthy controls (HCs) who received at least one dose of BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna) or ChAdOx1 (AstraZeneca/Oxford) between January 2021 and December 2022. Data from records, registries, questionnaires and blood samples collected June 2021–November 2023 were analysed. Primary outcomes were humoral immune responses assessed by seroconversion (anti-spike and anti-receptor-binding domain (RBD) IgG ≥5 binding antibody units/mL). Secondary outcomes included quantitative anti-RBD IgG levels, breakthrough SARS-CoV-2 infection, COVID-19-related hospitalisation and death. Associations with breakthrough infection were evaluated using multivariable logistic regression. Results: Among 3559 pwMS, 1201 received anti-CD20 monoclonal antibodies and 324 sphingosine-1-phosphate receptor (S1PR) modulators. After three vaccine doses, seroconversion was observed in 43.0% of anti-CD20-treated patients and 48.4% of S1PR-treated patients. In multivariable analysis, seroconversion was associated with lower risk of breakthrough infection (OR 0.67, 95% CI 0.58 to 0.78). During follow-up, 58 pwMS (1.6%) were hospitalised for COVID-19; 4 (0.1%) required non-invasive ventilatory support, no patients required invasive ventilation and no deaths occurred. Conclusions: Humoral vaccine responses were impaired in pwMS receiving anti-CD20 or S1PR therapies, but severe COVID-19 was rare. These findings support continued vaccination programmes and tailored protective measures for immunomodulated populations.

• Robertson, Anna Hayman; Wolf, Asia-Sophia Fumika Michaela; Fossum, Even; Solum, Guri; Bhandari, Sabin & Vikse, Elisabeth Lea [Show all 12 contributors for this article] (2026). Long-lasting cross-reactive and polyfunctional SARS-CoV-2 T cell responses in seniors are maintained after repeated vaccination and infections. Vaccine. ISSN 0264-410X. 80, p. 1–12. doi: 10.1016/j.vaccine.2026.128511. Full text in Research Archive
• Tunheim, Gro; Baranowska-Hustad, Marta Natalia; Lund-Johansen, Fridtjof; Fossum, Even; Bhandari, Sabin & Kukule, Liva [Show all 12 contributors for this article] (2025). SARS-CoV-2 Infection With Alpha B.1.1.7 Virus Induced Higher Antibody Responses Than Earlier Non-VOC Variants During the First Waves of the COVID-19 Pandemic in Norway. APMIS - Journal of Pathologiy, Microbiology and Immunology. ISSN 0903-4641. 133(12), p. 1–13. doi: 10.1111/apm.70102. Full text in Research Archive Show summary

  Antibody levels induced by SARS-CoV-2 infection have been reported to be associated with specific symptoms, disease severity, and viral load. In this study we investigated whether antibody responses were associated with virus type (Alpha B.1.1.7 or non-variants of concern (non-VOC)), viral load and clinical outcome in unvaccinated non-hospitalized adults with PCR-confirmed SARS-CoV-2 infection. Serum samples, questionnaires and symptom diaries were collected longitudinally (Day 0–180) between May 2020 and June 2021. IgG levels against ancestral Wuhan antigens and antibodies inhibiting RBD-ACE2 interaction were measured by multiplex immunoassay and flowcytometry, respectively. Antibody neutralization assays were performed with B.1 and B.1.1.7 viruses. Viral load was measured by digital-droplet PCR, and virus isolates were sequenced. Factors influencing IgG levels were investigated using Bayesian multilevel models. Alpha-cases had 2.6–3.2-fold higher IgG levels against RBD, nucleocapsid, and spike on Day 14, and higher antibody-mediated inhibition of ACE2-RBD interaction compared to non-VOC cases. Alpha-cases displayed 1.8-and 5.4-fold higher neutralizing antibody titers than non-VOC cases against B.1 and B1.1.7, respectively, but both non-VOC and Alpha cases displayed the lowest ratio of binding to neutralizing antibodies against their infecting virus type. Alpha cases reported more symptoms than non-VOC cases, but the severity of disease was similar. Nausea was significantly associated with higher IgG levels, while no association was found for viral load, despite Alpha cases having higher viral loads than non-VOC cases. This study shows higher antibody responses induced by the more transmissible Alpha virus compared to earlier non-VOC variants after mild SARS-CoV-2 infection. Reporting of nausea was positively associated with IgG levels.

• Aamodt, Anne Hege; Ueland, Thor; Boldingh, Marion Ingeborg; Bezgal, Burcu; Argren, Maria Bengtson Argren & Dunne, Cecilia Adele [Show all 29 contributors for this article] (2025). Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination. BMJ Neurology Open. 7(2). doi: 10.1136/bmjno-2024-001013. Full text in Research Archive Show summary

  Background and objectives Persistent headache has emerged as a symptom following acute COVID-19 and, to a lesser extent, after SARS-CoV-2 vaccination. However, the underlying mechanisms remain poorly understood. This study aimed to evaluate plasma levels of amyloid-related biomarkers in patients experiencing persistent headaches after COVID-19 or SARS-CoV-2 vaccination. Methods In this prospective observational cohort, patients presenting with severe headache as the dominating symptom after COVID-19 (n=29) or SARS-CoV-2 vaccination (n=31) had neurological assessments with reassessments after 6 months. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured using ELISA and compared with levels in healthy controls (n=16). Results We found a strong and persistent upregulation of APP in patients with headache after COVID-19 as compared with the two other groups. Notably, APP levels remained elevated at both inclusion and after 6 months in individuals with accompanying cognitive symptoms. In contrast, PZP levels were increased in patients with headache after SARS-CoV-2 vaccination at both time points relative to healthy controls. CTSL was only elevated in the post-COVID-19 at baseline, whereas SAA1 showed levels comparable across all groups. Conclusion Altered plasma levels of soluble markers, potentially reflecting changes in amyloid processing, were found in patients with persistent headache following SARS-CoV-2 vaccine, particularly in those with persistent headache after COVID-19. In the latter group, we also found some association with cognitive symptoms. Trial registration numbers NCT04576351 and NCT05235776 .

• Eggebø, Maria Stadheim; Heinzelbecker, Julia; Palashati, Heyilimu; Chandler, Nicholas John; Tran, Trung & Li, Yingqian [Show all 15 contributors for this article] (2025). TCR-engineered T cells targeting a shared β-catenin mutation eradicate solid tumors. Nature Immunology. ISSN 1529-2908. 26, p. 1726–1736. doi: 10.1038/s41590-025-02252-1. Full text in Research Archive Show summary

  HLA-bound peptides encoded by recurrent driver mutations are candidate targets for T cell-directed immunotherapy. Here we identify two neopeptides encoded by the CTNNB1S37F mutation presented on the frequent HLA-A*02:01 and HLA-A*24:02 molecules in cell lines naturally expressing the mutation and HLA alleles. This mutation leads to a gain of function in β-catenin and is estimated to occur in >7,000 new cancer cases annually in the United States. T cell receptors (TCRs) that specifically recognize the mutant peptides were isolated from naive healthy donor T cells. T cells redirected with CTNNB1-S37F TCRs efficiently killed CTNNB1S37F+ cell lines and patient-derived organoids in vitro and eradicated established tumors in a melanoma cell line mouse model and a patient-derived xenograft model of endometrial adenocarcinoma naturally expressing the mutation and the restricting HLA. We propose that TCR-T cells targeting CTNNB1-S37F can serve as a basis for solid cancer immunotherapy.

• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 32 contributors for this article] (2025). An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models. Nature Communications. 16(1), p. 1–16. doi: 10.1038/s41467-025-59353-6. Full text in Research Archive Show summary

  Although vaccines are usually given intramuscularly, the intranasal delivery route may lead to better mucosal protection and limit the spread of respiratory virus while easing administration and improving vaccine acceptance. The challenge, however, is to achieve delivery across the selective epithelial cell barrier. Here we report on a subunit vaccine platform, in which the antigen is genetically fused to albumin to facilitate FcRn-mediated transport across the mucosal barrier in the presence of adjuvant. Intranasal delivery in conventional and transgenic mouse models induces both systemic and mucosal antigen-specific antibody responses that protect against challenge with SARS-CoV-2 or influenza A. When benchmarked against an intramuscularly administered mRNA vaccine or an intranasally administered antigen fused to an alternative carrier of similar size, only the albumin-based intranasal vaccine yields robust mucosal IgA antibody responses. Our results thus suggest that this needle-free, albumin-based vaccine platform may be suited for vaccination against respiratory pathogens.

• Olofsson, Anna; Humbert, Marion; Rekha, Rokeya S.; Frankling, Maria Helde; Lund-Johansen, Fridtjof & Bergman, Peter [Show all 8 contributors for this article] (2025). Adaptive immune responses against common viruses are sustained and functional in end-of-life patients. iScience. 28(3). doi: 10.1016/j.isci.2025.112082. Full text in Research Archive Show summary

  Viral infections occur with increased frequency in patients in palliative care, impacting their quality of life and increasing mortality rates. Still, the function of the immune system has never been thoroughly studied at the end of life. We investigated virus-specific humoral and cellular immune responses in elderly end-of-life patients (n = 38) and controls (n = 28). Virus-specific T cell responses were characterized using high-parameter flow cytometry, after stimulation with cytomegalovirus (CMV) and human coronavirus OC43 peptides. Although some virus-specific T cells from patients exhibited elevated expression of costimulatory and coinhibitory molecules, their functional profile remained largely intact compared to controls. The expression of the cytotoxic markers Granzyme B, CD107a, and 2B4 on CMV-specific T cells correlated closely with survival time. Significantly, our data demonstrate that both humoral and cellular immunity remain responsive and functional against common viruses in end-of-life patients.

• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Show all 73 contributors for this article] (2024). High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 296(3), p. 249–259. doi: 10.1111/joim.13820. Full text in Research Archive Show summary

  Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

• Viermyr, Hans-Kittil; Tonby, Kristian; Ponzi, Erica; Trouillet-Assant, Sophie; Poissy, Julien & Arribas, José R. [Show all 49 contributors for this article] (2024). Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial. EBioMedicine. 111. doi: 10.1016/j.ebiom.2024.105511. Full text in Research Archive Show summary

  Background The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19. Methods Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status. Findings Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs. Interpretation This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size.

• Wolf, Asia-Sophia Fumika Michaela; Hammersbøen, Kristin Reine; Ørbo, Hilde Sofie Sager; Bhandari, Sabin; Solum, Guri & Kjønstad, Ingrid Fadum [Show all 30 contributors for this article] (2024). T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients on TNF inhibitor treatment: a prospective cohort study. EBioMedicine. 108. doi: 10.1016/j.ebiom.2024.105317. Full text in Research Archive Show summary

  Background Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. Methods This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2–4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. Findings Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. Interpretation Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines.

• Kared, Hassen; Jyssum, Ingrid; Alirezaylavasani, Amin; Egner, Ingrid Marie; Tran, Trung & Tietze, Lisa [Show all 17 contributors for this article] (2024). Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study. Frontiers in Immunology. 15:1296273, p. 1–12. doi: 10.3389/fimmu.2024.1296273. Full text in Research Archive Show summary

  Background: SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). Methods: We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. Findings: The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. Interpretation: SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.

• Alirezaylavasani, Amin; Egner, Ingrid Marie; Dahl, Tuva Børresdatter; Chopra, Adity; Kasahara, Taissa de Matos & Goll, Guro Løvik [Show all 15 contributors for this article] (2024). Deficient SARS-CoV-2 hybrid immunity during inflammatory bowel disease. Clinical Immunology. ISSN 1521-6616. 271, p. 1–13. doi: 10.1016/j.clim.2024.110404. Full text in Research Archive Show summary

  Patients with Inflammatory Bowel Disease (IBD) undergoing immunosuppressive therapies face heightened susceptibility to severe COVID-19. An in-depth understanding of systemic inflammation and cellular immune responses after SARS-CoV-2 vaccination and breakthrough infections (BTI) is required for optimizing vaccine strategies in this population. While the prevalence of high serological responders post- third COVID-19 vaccine dose was lower, and the antibody waning was higher in IBD patients than in healthy donors (HD), IBD patients showed an increase in anti-RBD Wild Type IgG levels and cross-reactive Spike -specific memory B cells following BTI. However, there was no significant enhancement in cellular immune responses against anti-SARS-CoV-2 post-BTI, with responses instead characterized by activation of SARS-CoV-2 specific and also bystander CD8 T cells. These results suggest a complex interaction between chronic inflammation in IBD and the generation of new immune responses, highlighting the need for tailored vaccine regimens and anti-inflammatory therapies to boost cellular immunity against SARS-CoV-2.

• Wüsthoff, Linda Elise Couëssurel; Lund-Johansen, Fridtjof; Henriksen, Kathleen; Wildendahl, Gull; Jacobsen, Jon-Aksel & Gomes, Leni [Show all 11 contributors for this article] (2024). Seroprevalence of SARS-CoV-2 and humoral immune responses to COVID-19 mRNA vaccines among people who use drugs - in the light of tailored mitigating strategies. Harm Reduction Journal. 21(1). doi: 10.1186/s12954-024-01023-9. Full text in Research Archive Show summary

  Background During the initial wave of the COVID-19 pandemic, there was a surprisingly low incidence of SARS-CoV-2 among People Who Use Drugs (PWUD) in Oslo, Norway, despite their heightened vulnerability regarding risk of infection and severe courses of the disease.This study aims to investigate the seroprevalence of SARS-CoV-2 antibodies among PWUD, their antibody responses to relevant virus infections and COVID-19 mRNA vaccines, and their vaccination coverage compared to the general population. Methods Conducted as a prospective cohort study, data was collected from residents in six institutions for homeless PWUD and users of a low-threshold clinic for opioid agonist treatment. Ninety-seven participants were recruited for SARS-CoV-2 seroprevalence analysis. Additional two participants with known positive SARS-CoV-2 test results were recruited for further analyses. Twenty-five participants completed follow-up. Data included questionnaires, nasal swabs and blood samples. Data on vaccination coverage was obtained from the National Vaccine Register. Serologic methods included detection of antibodies to relevant virus proteins, neutralizing antibodies to SARS-CoV-2, antibodies to the full-length spike protein, and receptor-binding domain from SARS-CoV-2. Results Among PWUD, antibodies to SARS-CoV-2 were detected in 2 out of 97 samples before vaccines against SARS-CoV-2 were available, comparable to a 2.8% frequency in population-based screening. Levels of serum antibodies to seasonal coronaviruses and Epstein-Barr-Virus (EBV) in PWUD were similar to population-based levels. After the second vaccine dose, binding and neutralizing antibody levels to SARS-CoV-2 in PWUD were comparable to controls. Eighty-four of PWUD received at least one dose of COVID-19 mRNA vaccine, compared to 89% in the general population. Conclusion Results indicate that PWUD did not exhibit increased SARS-CoV-2 seroprevalence or elevated serum antibodies to seasonal coronaviruses and EBV. Moreover, vaccine responses in PWUD were comparable to controls, suggesting that vaccination is effective in conferring protection against SARS-CoV-2 also in this population.

• Alirezaylavasani, Amin; Skeie, Linda Gail; Egner, Ingrid Marie; Chopra, Adity; Dahl, Tuva Børresdatter & Prebensen, Christian Haugland [Show all 16 contributors for this article] (2024). Vaccine responses and hybrid immunity in people living with HIV after SARS-CoV-2 breakthrough infections. npj Vaccines. 9(1), p. 1–15. doi: 10.1038/s41541-024-00972-3. Full text in Research Archive Show summary

  The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count <350 cells per mm3). Their diminished vaccine responses raised concerns about their vulnerability to SARS-CoV-2 breakthrough infections (BTI). Our in-depth study here revealed chronic inflammation in PLWH and a limited anti-Spike IgG response after vaccination in INR. Nevertheless, the imprinting of Spike-specific B cells by vaccination significantly enhanced the humoral responses after BTI. Notably, the magnitude of cellular CD4 response in all PLWH was comparable to that in healthy donors (HD). However, the polyfunctionality and phenotype of Spike-specific CD8 T cells in INR differed from controls. The findings highlight the need for additional boosters with variant vaccines, and for monitoring ART adherence and the durability of both humoral and cellular anti-SARS-CoV-2 immunity in INR.

• Scheffer, Lonneke; Reber, Eric Emanuel; Mehta, Brij Bhushan; Pavlović, Milena; Chernigovskaia, Maria & Richardson, Eve [Show all 11 contributors for this article] (2024). Predictability of antigen binding based on short motifs in the antibody CDRH3. Briefings in Bioinformatics. ISSN 1467-5463. 25(6), p. 1–10. doi: 10.1093/bib/bbae537. Full text in Research Archive Show summary

  Adaptive immune receptors, such as antibodies and T-cell receptors, recognize foreign threats with exquisite specificity. A major challenge in adaptive immunology is discovering the rules governing immune receptor–antigen binding in order to predict the antigen binding status of previously unseen immune receptors. Many studies assume that the antigen binding status of an immune receptor may be determined by the presence of a short motif in the complementarity determining region 3 (CDR3), disregarding other amino acids. To test this assumption, we present a method to discover short motifs which show high precision in predicting antigen binding and generalize well to unseen simulated and experimental data. Our analysis of a mutagenesis-based antibody dataset reveals 11 336 position-specific, mostly gapped motifs of 3–5 amino acids that retain high precision on independently generated experimental data. Using a subset of only 178 motifs, a simple classifier was made that on the independently generated dataset outperformed a deep learning model proposed specifically for such datasets. In conclusion, our findings support the notion that for some antibodies, antigen binding may be largely determined by a short CDR3 motif. As more experimental data emerge, our methodology could serve as a foundation for in-depth investigations into antigen binding signals.

• Tunheim, Gro; Fossum, Even; Robertson, Anna Hayman; Rø, Gunnar Øyvind Isaksson; Chopra, Adity & Vaage, John T. [Show all 13 contributors for this article] (2024). Characterization of the SARS-CoV-2 antibody landscape in Norway in the late summer of 2022: high seroprevalence in all age groups with patterns of primary Omicron infection in children and hybrid immunity in adults. BMC Infectious Diseases. 24:841(1), p. 1–20. doi: 10.1186/s12879-024-09670-w. Full text in Research Archive Show summary

  Background According to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera. Methods 1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1. Results The national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1. Conclusions By late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants.

• Strunz, Benedikt; Maucourant, Christopher; Mehta, Adi; Wan, Hui; Du, Likun & Sun, Dan [Show all 26 contributors for this article] (2024). Type I Interferon Autoantibodies Correlate With Cellular Immune Alterations in Severe COVID-19. Journal of Infectious Diseases. ISSN 0022-1899. 230(2), p. e318–e326. doi: 10.1093/infdis/jiae036. Full text in Research Archive Show summary

  Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). Methods This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. Results aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. Conclusions Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.

• Ravussin, Anthony; Robertson, Anna Hayman; Wolf, Asia-Sophia Fumika Michaela; Blix, Kristine; Kjønstad, Ingrid Fadum & Solum, Guri [Show all 13 contributors for this article] (2023). Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study. The Lancet Healthy Longevity. 4(5), p. e188–e199. doi: 10.1016/S2666-7568(23)00055-7. Full text in Research Archive Show summary

  Background Older age is associated with poorer outcomes to COVID-19 infection. The Norwegian Institute of Public Health established a longitudinal cohort of adults aged 65–80 years to study the effects of the COVID-19 pandemic. Here we describe the characteristics of the cohort in general, and specifically the immune responses at baseline and after primary and booster vaccination in a subset of longitudinal blood samples, and the epidemiological factors affecting these responses. Methods 4551 participants were recruited, with humoral (n=299) and cellular (n=90) responses measured before vaccination and after two and three vaccine doses. Information on general health, infections, and vaccinations were obtained from questionnaires and national health registries. Findings Half of the participants had a chronic condition. 849 (18·7%) of 4551 were prefrail and 184 (4%) of 4551 were frail. 483 (10·6%) of 4551 had general activity limitations (scored with the Global Activity Limitation Index). After dose two, 295 (98·7%) of 299 participants were seropositive for anti-receptor binding domain IgG, and 210 (100%) of 210 participants after dose three. Spike-specific CD4 and CD8 T cell responses showed high heterogeneity after vaccination and responded to the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529 or BA.1) variants of concern. Cellular responses to seasonal coronaviruses increased after SARS-CoV-2 vaccination. Heterologous prime boosting with mRNA vaccines was associated with the highest antibody (p=0·019) and CD4 T cell responses (p=0·003), and hypertension with lower antibody levels after three doses (p=0·04). Interpretation Most older adults, including those with comorbidities, generated good serological and cellular responses after two vaccine doses. Responses further improved after three doses, particularly after heterologous boosting. Vaccination also generated cross-reactive T cells against variants of concern and seasonal coronaviruses. Frailty was not associated with impaired immune responses, but hypertension might indicate reduced responsiveness to vaccines even after three doses. Individual differences identified through longitudinal sampling enables better prediction of the variability of vaccine responses, which can help guide future policy on the need for subsequent doses and their timing.

• Amstutz, Alain; Speich, Benjamin; Mentré, France; Rüegg, Corina Silvia; Belhadi, Drifa & Assoumou, Lambert [Show all 35 contributors for this article] (2023). Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials. The Lancet Respiratory Medicine. ISSN 2213-2600. 11(5), p. 453–464. doi: 10.1016/S2213-2600(22)00528-8. Full text in Research Archive
• Földvári, Zsofia; Knetter, Cathrine; Yang, Weiwen; Gjerdingen, Thea Johanne; Bollineni, Ravi Chand & Tran, Trung [Show all 12 contributors for this article] (2023). A systematic safety pipeline for selection of T-cell receptors to enter clinical use. npj Vaccines. 8(1). doi: 10.1038/s41541-023-00713-y. Full text in Research Archive
• Humbert, Marion; Olofsson, Anna; Wullimann, David; Niessl, Julia; Hodcroft, Emma B. & Cai, Curtis [Show all 20 contributors for this article] (2023). Functional SARS-CoV-2 cross-reactive CD4⁺ T cells established in early childhood decline with age. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 120(12). doi: 10.1073/pnas.2220320120. Full text in Research Archive Show summary

  Significance Our results provide evidence that functional pre-existing SARS-CoV-2-reactive memory CD4+ T cells are elicited in early childhood and linked to seroconversion with the seasonal coronavirus OC43 but not many other viral infections. Compared to other viruses, the high OC43 seroprevalence at age two indicates that memory responses to coronaviruses develop at a young age. The distinct age-dependent profiles of the responding T cells suggest that cross-reactive T cells can contribute to the different clinical outcomes of COVID-19 in children and the elderly. The present results provide important advances regarding antigen-specific memory CD4+ T cell development and maturation, which can help guide future vaccine and therapeutic interventions relating to specificity, function, and phenotype of memory T cell responses throughout the human life span. Abstract Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein–Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.

• Kared, Hassen; Alirezaylavasani, Amin; Lund, Kathrine Persgård; Chopra, Adity; Tietze, Lisa & Kasahara, Taissa de Matos [Show all 17 contributors for this article] (2023). Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipients. EBioMedicine. 97. doi: 10.1016/j.ebiom.2023.104833. Full text in Research Archive Show summary

  Background Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection. Methods We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3–4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors. Findings After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG+ B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5–6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses. Interpretation Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.

• Trøseid, Marius; Arribas, José R.; Assoumou, Lambert; Holten, Aleksander Rygh; Poissy, Julien & Terzić, Vida [Show all 56 contributors for this article] (2023). Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID‑19 (Bari‑SolidAct): a randomised, double‑blind, placebo‑controlled phase 3 trial. Critical Care. ISSN 1364-8535. 27(9), p. 1–15. doi: 10.1186/s13054-022-04205-8. Full text in Research Archive Show summary

  Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies.

• Selvakumar, Joel Pradeepkumar; Havdal, Lise Beier; Drevvatne, Martin Solstrand; Brodwall, Elias Myrstad; Lund-Berven, Lise & Stiansen-Sonerud, Tonje [Show all 19 contributors for this article] (2023). Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults. JAMA Network Open. 6(3). doi: 10.1001/jamanetworkopen.2023.5763. Full text in Research Archive Show summary

  Importance The prevalence and baseline risk factors of post–COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription–polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures SARS-CoV-2 infection. Main Outcomes and Measures The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2–positive and SARS-CoV-2–negative groups, and the risk difference with corresponding 95% CIs. Results A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2–positive and 4 of the SARS-CoV-2–negative individuals were lost to follow-up, and 16 SARS-CoV-2–negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2–positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2–negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2–positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, −10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC.

• Nissen-Meyer, Lise Sofie Haug; Macpherson, Magnhild Eide; Skeie, Linda Gail; Hvalryg, Marte; LLOHN, ABID HUSSAIN & Steinsvåg, Tine Torsvik [Show all 17 contributors for this article] (2023). Covid-19-pasienter behandlet med rekonvalesensplasma. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(11). doi: 10.4045/tidsskr.22.0577. Full text in Research Archive Show summary

  BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke. RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.

• Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; König, Marton; Øverås, Mathias Herstad; Solum, Guri & Kjønstad, Ingrid Fadum [Show all 18 contributors for this article] (2023). T cell responses to SARS-CoV-2 vaccination differ by disease-modifying therapy for multiple sclerosis. JCI Insight. 8(12), p. 1–14. doi: 10.1172/jci.insight.165111. Full text in Research Archive Show summary

  Immune responses in people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have been of significant interest throughout the COVID-19 pandemic. Lymphocyte-targeting immunotherapies, including anti-CD20 treatments and sphingosine-1-phosphate receptor (S1PR) modulators, attenuate Ab responses after vaccination. Evaluation of cellular responses after vaccination, therefore, is of particular importance in these populations. In this study, we used flow cytometry to analyze CD4 and CD8 T cell functional responses to SARS-CoV-2 spike peptides in healthy control study participants and pwMS receiving 5 different DMTs. Although pwMS receiving rituximab and fingolimod therapies had low Ab responses after both 2 and 3 vaccine doses, T cell responses in pwMS taking rituximab were preserved after a third vaccination, even when an additional dose of rituximab was administered between vaccine doses 2 and 3. PwMS taking fingolimod had low detectable T cell responses in peripheral blood. CD4 and CD8 T cell responses to SARS-CoV-2 variants of concern Delta and Omicron were lower than to the ancestral Wuhan-Hu-1 variant. Our results indicate the importance of assessing both cellular and humoral responses after vaccination and suggest that, even in the absence of robust Ab responses, vaccination can generate immune responses in pwMS.

• Nissen-Meyer, Lise Sofie Haug; Steinsvåg, Christine Torsvik; Fenstad, Mona H.; Sørvoll, Ingvild Hausberg; Hvalryg, Marte & Titze, Thomas Larsen [Show all 20 contributors for this article] (2023). Rekonvalesensplasma mot covid-19 fremstilt fra norske blodgivere. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(11), p. 953–957. doi: 10.4045/tidsskr.22.0180. Full text in Research Archive Show summary

  BAKGRUNN I Norge er behandling med covid-19-rekonvalesensplasma gitt gjennom NORPLASMA-prosjektet. I begynnelsen ble behandlingen tilbudt kritisk syke pasienter etter individuell vurdering, men fra desember 2020 ble indikasjonen begrenset til kritisk syke pasienter med immunsvikt. Vi beskriver her kliniske karakteristika, komorbiditet og mortalitet hos pasienter som fikk rekonvalesensplasma i disse to periodene. MATERIALE OG METODE I perioden 22.4.2020–30.3.2022 ble 79 pasienter inkludert i observasjonsstudiene NORPLASMA MONITOR og Norwegian SARS-CoV-2-studien. Pasientene hadde mottatt totalt 193 enheter med rekonvalesensplasma ved 15 norske sykehus/sykehjem: 62 i Helse Sør-Øst, 8 i Helse Vest og 9 i Helse Midt-Norge. Opplysninger om immunstatus, komorbiditet og sykdomsforløp ble registrert fra pasientjournalen etter skriftlig samtykke.RESULTATER Av 79 pasienter med median alder 65 år (interkvartilbredde 51–73) som fikk behandling med rekonvalesensplasma, døde 31 (39 %) under sykehusoppholdet. 59 pasienter hadde immunsvikt, og blant disse døde 20 i sykehus, mot 11 av 20 antatt immunkompetente. Median antall komorbiditeter var 2 (interkvartilbredde 1–4). Pasientene fikk i median 2 plasmaenheter (min–maks 1–21). To av pasientene utviklet milde allergiske hudreaksjoner. FORTOLKNING Rekonvalesensplasma ble godt tolerert av pasienter med covid-19. Immunsviktpasienter hadde muligens effekt av behandlingen, med lavere dødelighet i denne gruppen enn blant antatt immunkompetente.

• Åsberg, Anders; Hovd, Markus Herberg; Kjellevold, Stig Arne; Stenehjem, Aud Eldrid; Wien, Tale Norbye & Broch, Lars Ulrik [Show all 15 contributors for this article] (2023). Humoral Response After 6 or More Successive Doses of SARS-CoV-2 mRNA Vaccines in Kidney Transplant Recipients-Should We Keep Vaccinating? Transplantation. ISSN 0041-1337. 107(10), p. e279–e280. doi: 10.1097/TP.0000000000004732. Full text in Research Archive
• Jørgensen, Kristin Kaasen; Høivik, Marte Lie; Chopra, Adity; Benth, Jurate Saltyte; Ricanek, Petr & Moum, Bjørn Allan [Show all 18 contributors for this article] (2023). Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(8), p. 874–882. doi: 10.1080/00365521.2023.2177884. Full text in Research Archive Show summary

  Objectives Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. Materials and methods This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. Results In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Conclusions Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

• Gainullin, Murat; Federico, Lorenzo; Osen, Julie Røkke; Chaban, Viktoriia; Kared, Hassen & Alirezaylavasani, Amin [Show all 18 contributors for this article] (2023). People who use drugs show no increase in pre-existing T-cell cross-reactivity toward SARS-CoV-2 but develop a normal polyfunctional T-cell response after standard mRNA vaccination. Frontiers in Immunology. 14:1235210, p. 1–13. doi: 10.3389/fimmu.2023.1235210. Full text in Research Archive Show summary

  People who use drugs (PWUD) are at a high risk of contracting and developing severe coronavirus disease 2019 (COVID-19) and other infectious diseases due to their lifestyle, comorbidities, and the detrimental effects of opioids on cellular immunity. However, there is limited research on vaccine responses in PWUD, particularly regarding the role that T cells play in the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we show that before vaccination, PWUD did not exhibit an increased frequency of preexisting cross-reactive T cells to SARS-CoV-2 and that, despite the inhibitory effects that opioids have on T-cell immunity, standard vaccination can elicit robust polyfunctional CD4 + and CD8 + T-cell responses that were similar to those found in controls. Our findings indicate that vaccination stimulates an effective immune response in PWUD and highlight targeted vaccination as an essential public health instrument for the control of COVID-19 and other infectious diseases in this group of high-risk patients.

• Hovd, Markus Herberg; Åsberg, Anders; Munthe, Ludvig Andre; Heldal, Kristian; Reisæter, Anna Varberg & Vaage, John T. [Show all 8 contributors for this article] (2023). Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study. EClinicalMedicine. 60. doi: 10.1016/j.eclinm.2023.102035. Full text in Research Archive Show summary

  Background Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4–10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings The study included 3607 KTRs (59 [48–70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3–4] vaccines (range 2–6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31–57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.

• Federico, Lorenzo; Tvedt, Tor Henrik Anderson; Gainullin, Murat; Osen, Julie Røkke; Chaban, Viktoriia & Lund, Kathrine Persgård [Show all 19 contributors for this article] (2023). Robust spike-specific CD4⁺ and CD8⁺ T cell responses in SARS-CoV-2 vaccinated hematopoietic cell transplantation recipients: a prospective, cohort study. Frontiers in Immunology. 14. doi: 10.3389/fimmu.2023.1210899. Full text in Research Archive Show summary

  Poor overall survival of hematopoietic stem cell transplantation (HSCT) recipients who developed COVID-19 underlies the importance of SARS-CoV-2 vaccination. Previous studies of vaccine efficacy have reported weak humoral responses but conflicting results on T cell immunity. Here, we have examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna’s mRNA-1273 or Pfizer/BioNTech’s BNT162b2 vaccines. Nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses, with 18/48 (37%, IQR 8.679-5601 BAU/mL) displaying protective IgG anti-receptor binding domain (RBD) levels (&amp;gt;2000 BAU/mL). Flow cytometry analysis of activation induced markers (AIMs) revealed that 90% and 74% of HSCT patients showed reactivity towards immunodominant spike peptides in CD8 + and CD4 + T cells, respectively. The response rate increased to 90% for CD4 + T cells as well when we challenged the cells with a complete set of overlapping peptides spanning the entire spike protein. T cell response was detectable as early as 3 months after transplant, but only CD4 + T cell reactivity correlated with IgG anti-RBD level and time after transplantation. Boosting increased seroconversion rate, while only one patient developed COVID-19 requiring hospitalization. Our data suggest that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.

• Meyer, Saskia; Blaas, Isaac; Bollineni, Ravi Chand; Delic-Sarac, Marina; Tran, Trung & Knetter, Cathrine [Show all 20 contributors for this article] (2023). Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants. Cell reports. 42(1). doi: 10.1016/j.celrep.2023.111995. Full text in Research Archive Show summary

  The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. 7(1). doi: 10.1038/s41541-022-00586-7. Full text in Research Archive Show summary

  Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

• Anda, Erik Eik; Braaten, Tonje Bjørndal; Borch, Kristin Benjaminsen; Nøst, Therese Haugdahl; Chen, Sairah Lai Fa & Lukic, Marko [Show all 14 contributors for this article] (2022). Seroprevalence of antibodies against SARS-CoV-2 in the adult population during the pre-vaccination period, Norway, winter 2020/21. Eurosurveillance. ISSN 1025-496X. 27(13), p. 1–10. doi: 10.2807/1560-7917.ES.2022.27.13.2100376. Full text in Research Archive Show summary

  Background: Since March 2020, 440 million people worldwide have been diagnosed with COVID-19, but the true number of infections with SARS-CoV-2 is higher. SARS-CoV-2 antibody seroprevalence can add crucial epidemiological information about population infection dynamics. Aim: To provide a large population-based SARS-CoV-2 seroprevalence survey from Norway; we estimated SARS-CoV-2 seroprevalence before introduction of vaccines and described its distribution across demographic groups. Methods: In this population-based cross-sectional study, a total of 110,000 people aged 16 years or older were randomly selected during November–December 2020 and invited to complete a questionnaire and provide a dried blood spot (DBS) sample. Results: The response rate was 30% (31,458/104,637); compliance rate for return of DBS samples was 88% (27,700/31,458). National weighted and adjusted seroprevalence was 0.9% (95% CI (confidence interval): 0.7–1.0). Seroprevalence was highest among those aged 16–19 years (1.9%; 95% CI: 0.9–2.9), those born outside the Nordic countries 1.4% (95% CI: 1.0–1.9), and in the counties of Oslo 1.7% (95% CI: 1.2–2.2) and Vestland 1.4% (95% CI: 0.9– 1.8). The ratio of SARS-CoV-2 seroprevalence (0.9%) to cumulative incidence of virologically detected cases by mid-December 2020 (0.8%) was slightly above one. SARS-CoV-2 seroprevalence was low before introduction of vaccines in Norway and was comparable to virologically detected cases, indicating that most cases in the first 10 months of the pandemic were detected. Conclusion: Findings suggest that preventive measures including contact tracing have been effective, people complied with physical distancing recommendations, and local efforts to contain outbreaks have been essential.

• Lee, Yunsung; Riskedal, Espen; Kalleberg, Karl Trygve; Istre, Mette Stausland; Lind, Andreas & Lund-Johansen, Fridtjof [Show all 12 contributors for this article] (2022). EWAS of post-COVID-19 patients shows methylation differences in the immune-response associated gene, IFI44L, three months after COVID-19 infection. Scientific Reports. 12(1). doi: 10.1038/s41598-022-15467-1. Full text in Research Archive Show summary

  Although substantial progress has been made in managing COVID-19, it is still difficult to predict a patient’s prognosis. We explored the epigenetic signatures of COVID-19 in peripheral blood using data from an ongoing prospective observational study of COVID-19 called the Norwegian Corona Cohort Study. A series of EWASs were performed to compare the DNA methylation profiles between COVID-19 cases and controls three months post-infection. We also investigated differences associated with severity and long-COVID. Three CpGs—cg22399236, cg03607951, and cg09829636—were significantly hypomethylated (FDR < 0.05) in COVID-19 positive individuals. cg03607951 is located in IFI44L which is involved in innate response to viral infection and several systemic autoimmune diseases. cg09829636 is located in ANKRD9, a gene implicated in a wide variety of cellular processes, including the degradation of IMPDH2. The link between ANKRD9 and IMPDH2 is striking given that IMPDHs are considered therapeutic targets for COVID-19. Furthermore, gene ontology analyses revealed pathways involved in response to viruses. The lack of significant differences associated with severity and long-COVID may be real or reflect limitations in sample size. Our findings support the involvement of interferon responsive genes in the pathophysiology of COVID-19 and indicate a possible link to systemic autoimmune diseases.

• Ibsen, Jostein Holen; Chopra, Adity; Vaage, Eline Benno; Vaage, John T.; Lund-Johansen, Fridtjof & Lundin, Knut (2022). Immune responses to SARS-CoV-2 vaccines in celiac disease. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 00(0). doi: 10.1080/00365521.2022.2114809. Full text in Research Archive Show summary

  Background and aims SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. Methods CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. Results Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). Conclusion The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.

• Kared, Hassen; Wolf, Asia-Sophia Fumika Michaela; Alirezaylavasani, Amin; Ravussin, Anthony; Solum, Guri & Tran, Trung [Show all 17 contributors for this article] (2022). Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults. Nature Communications. 13(1). doi: 10.1038/s41467-022-31888-y. Full text in Research Archive Show summary

  Abstract The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (T FH ) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG + B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.

• Robert, Philippe Paul Auguste; Akbar, Rahmad; Frank, Robert; Pavlović, Milena; Widrich, Michael & Snapkov, Igor [Show all 25 contributors for this article] (2022). Unconstrained generation of synthetic antibody–antigen structures to guide machine learning methodology for antibody specificity prediction. Nature Computational Science. 2(12), p. 845–865. doi: 10.1038/s43588-022-00372-4. Full text in Research Archive
• Granerud, Beathe Kiland; Ueland, Thor; Lind, Andreas; Søraas, Arne Vasli; Fevang, Børre & Steffensen, Anne Katrine [Show all 14 contributors for this article] (2022). Omicron Variant Generates a Higher and More Sustained Viral Load in Nasopharynx and Saliva Than the Delta Variant of SARS-CoV-2. Viruses. 14(11). doi: 10.3390/v14112420. Full text in Research Archive Show summary

  The Omicron variant of SARS-CoV-2 spreads more easily than earlier variants, possibly as a result of a higher viral load in the upper respiratory tract and oral cavity. Hence, we investigated whether the Omicron variant generates a higher viral load than that of the Delta variant in saliva and nasopharynx. Both specimens were collected from 52 Omicron and 17 Delta cases at two time points one week apart and analyzed by qRT-PCR. Viral load was measured as 10 log RNA genome copies per 1000 human cells according to the WHO reference standard. We found that Omicron cases carried a higher viral load and had more sustained viral shedding compared to the Delta cases, especially in the nasopharynx.

• Syversen, Silje Watterdal; Jyssum, Ingrid; Tveter, Anne Therese; Tran, Trung; Sexton, Joseph & Provan, Sella Aarrestad [Show all 22 contributors for this article] (2022). Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy. Arthritis & Rheumatology. ISSN 2326-5191. 74(8), p. 1321–1332. doi: 10.1002/art.42153. Full text in Research Archive Show summary

  Objective Immunogenicity and safety following receipt of the standard SARS–CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS–CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. Methods Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS–CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS–CoV-2 spike protein were performed prior to and 2–4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS–Cov-2 spike protein, were allotted a third vaccine dose. Results A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192–4,191) than in controls (median 3,355 AU/ml [IQR 896–7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA–1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. Conclusion IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

• Sommen, Silke Lauren; Havdal, Lise Beier; Selvakumar, Joel Pradeepkumar; Einvik, Gunnar; Leegaard, Truls Michael & Lund-Johansen, Fridtjof [Show all 12 contributors for this article] (2022). Inflammatory markers and pulmonary function in adolescents and young adults 6 months after mild COVID-19. Frontiers in Immunology. 13, p. 1–12. doi: 10.3389/fimmu.2022.1081718. Full text in Research Archive Show summary

  Introduction: Both public and scientific attention have shifted from the acute COVID-19 illness to the chronic disability experienced by a proportion of COVID-19 convalescents. Post COVID-19 condition, a term used for long-lasting symptoms after COVID-19, can affect individuals across all disease severity and age groups. Data on post-COVID-19 symptomatology, epidemiology and pathophysiology in adolescents and young adults are scarce. To date, little is known on the immunological and pulmonary trends in these patients after COVID-19. This study investigated immunological markers and pulmonary function in non-hospitalized patients in this group at 6 months after initial mild COVID-19 infection. Methods: Non-hospitalized SARS-CoV-2 positive (n = 405) and SARS-CoV-2 negative (n = 111) adolescents and young adults (aged 12-25 years) were followed prospectively for six months after SARS-CoV-2 PCR testing. At baseline and at six months follow-up, all participants underwent an assessment including clinical examination, questionnaires, spirometry, and blood sampling. Cross-sectional comparisons of blood biomarkers; including white blood cell counts, CRP, GDF-15, a 27-multiplex cytokine assay, complement activation products and SARS-CoV-2 antibodies; and spirometry measures were performed after classification of all participants according to their COVID-19 status and adherence to post-COVID-19 case criteria. Associations between biomarkers and COVID-19 symptoms were explored. Results: No difference in pulmonary function was detected between the groups. COVID-19 convalescents had higher levels of chemokines eotaxin, MCP-1 and IP-10 than non-infected controls. The increase was modest and not associated with long-lasting COVID-19 symptoms. Discussion: Elevated inflammatory mediators were found in adolescents and young adults six months after mild COVID-19, but there was no association with post-COVID-19 condition.

• Didriksen, Henriette; Molberg, Øyvind; Mehta, Adi; Jordan, Suzana; Palchevskiy, Vyacheslav & Fretheim, Håvard Halland [Show all 16 contributors for this article] (2022). Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension. Frontiers in Immunology. 13. doi: 10.3389/fimmu.2022.991743. Full text in Research Archive Show summary

  Introduction Systemic sclerosis (SSc) is a heterogenous disorder that appears to result from interplay between vascular pathologies, tissue fibrosis and immune processes, with evidence for deregulation of chemokines, which normally control immune trafficking. We recently identified altered levels of chemokine CCL21 in SSc associated pulmonary arterial hypertension (PAH). Here, we aimed to define target organ expression and biomarker characteristics of CCL21. Materials and methods To investigate target organ expression of CCL21, we performed immunohistochemistry (IHC) on explanted lung tissues from SSc-PAH patients. We assessed serum levels of CCL21 by ELISA and Luminex in two well-characterized SSc cohorts from Oslo (OUH, n=552) and Zurich (n=93) University hospitals and in 168 healthy controls. For detection of anti-CCl21 antibodies, we performed protein array analysis applying serum samples from SSc patients (n=300) and healthy controls. To characterize circulating CCL21 in SSc, we applied immunoprecipitation (IP) with antibodies detecting both full length and tailless and a custom-made antibody detecting only the C-terminal of CCL21. IP products were analyzed by SDS-PAGE/western blot and Mass spectrometry (MS). Results By IHC, we found that CCL21 was mainly expressed in the airway epithelial cells of SSc patients with PAH. In the analysis of serum levels of CCL21 we found weak correlation between Luminex and ELISA (r=0.515, p&amp;lt;0.001). Serum levels of anti-CCL21 antibodies were higher in SSc patients than in healthy controls (p&amp;lt;0.001), but only 5% of the SSc population were positive for anti-CCL21 antibodies in SSc, and we found no correlation between anti-CCl21 and serum levels of CCL21. By MS, we only identified peptides located within amino acid (aa) 23-102 of CCL21, indicating that CCL21 in SSc circulate as a truncated protein without the C-terminal tail. Conclusion This study demonstrates expression of CCL21 in epithelial lung tissue from SSc patients with PAH, and indicate that CCL21 in SSc circulates as a truncated protein. We extend previous observations indicating biomarker potential of CCL21, but find that Luminex is not suitable as platform for biomarker analyses. Finally, in vivo generated anti-CCL21 antibodies exist in SSc, but do not appear to modify serum CCL21 levels in patients with SSc-PAH.

• Søraas, Arne Vasli; Grødeland, Gunnveig; Granerud, Beathe Kiland; Ueland, Thor; Lind, Andreas & Fevang, Børre [Show all 32 contributors for this article] (2022). Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity. Frontiers in Immunology. 13:964525, p. 1–12. doi: 10.3389/fimmu.2022.964525. Full text in Research Archive Show summary

  Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals. Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters. Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant.

• Akbar, Rahmad; Bashour, Habib; Rawat, Puneet; Robert, Philippe Paul Auguste; Smorodina, Eva & Cotet, Tudor-Stefan [Show all 15 contributors for this article] (2022). Progress and challenges for the machine learning-based design of fit-for-purpose monoclonal antibodies. mAbs. ISSN 1942-0862. 14:e2008790(1), p. 1–35. doi: 10.1080/19420862.2021.2008790. Full text in Research Archive Show summary

  Although the therapeutic efficacy and commercial success of monoclonal antibodies (mAbs) are tremendous, the design and discovery of new candidates remain a time and cost-intensive endeavor. In this regard, progress in the generation of data describing antigen binding and developability, computational methodology, and artificial intelligence may pave the way for a new era of in silico on-demand immunotherapeutics design and discovery. Here, we argue that the main necessary machine learning (ML) components for an in silico mAb sequence generator are: understanding of the rules of mAb-antigen binding, capacity to modularly combine mAb design parameters, and algorithms for unconstrained parameter-driven in silico mAb sequence synthesis. We review the current progress toward the realization of these necessary components and discuss the challenges that must be overcome to allow the on-demand ML-based discovery and design of fit-for-purpose mAb therapeutic candidates.

• Riise, Jon; Meyer, Saskia; Blaas, Isaac; Chopra, Adity; Tran, Trung & Delic-Sarac, Marina [Show all 22 contributors for this article] (2022). Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination. British Journal of Haematology. ISSN 0007-1048. 197(6), p. 697–708. doi: 10.1111/bjh.18149. Full text in Research Archive Show summary

  B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.

• König, Marton; Torgauten, Hilde Marie; Tran, Trung; Holmøy, Trygve; Vaage, John T. & Lund-Johansen, Fridtjof [Show all 7 contributors for this article] (2022). Immunogenicity and Safety of a Third SARS-CoV-2 Vaccine Dose in Patients with Multiple Sclerosis and Weak Immune Response after COVID-19 Vaccination. JAMA Neurology. ISSN 2168-6149. 79(3), p. 307–309. doi: 10.1001/jamaneurol.2021.5109. Full text in Research Archive
• Akbar, Rahmad; Robert, Philippe Paul Auguste; Weber, Cédric R.; Widrich, Michael; Frank, Robert & Pavlovic, Milena [Show all 19 contributors for this article] (2022). In silico proof of principle of machine learning-based antibody design at unconstrained scale. mAbs. ISSN 1942-0862. 14:e2031482(1), p. 1–18. doi: 10.1080/19420862.2022.2031482. Full text in Research Archive Show summary

  Generative machine learning (ML) has been postulated to become a major driver in the computational design of antigen-specific monoclonal antibodies (mAb). However, efforts to confirm this hypothesis have been hindered by the infeasibility of testing arbitrarily large numbers of antibody sequences for their most critical design parameters: paratope, epitope, affinity, and developability. To address this challenge, we leveraged a lattice-based antibody-antigen binding simulation framework, which incorporates a wide range of physiological antibody-binding parameters. The simulation framework enables the computation of synthetic antibody-antigen 3D-structures, and it functions as an oracle for unrestricted prospective evaluation and benchmarking of antibody design parameters of ML-generated antibody sequences. We found that a deep generative model, trained exclusively on antibody sequence (one dimensional: 1D) data can be used to design conformational (three dimensional: 3D) epitope-specific antibodies, matching, or exceeding the training dataset in affinity and developability parameter value variety. Furthermore, we established a lower threshold of sequence diversity necessary for high-accuracy generative antibody ML and demonstrated that this lower threshold also holds on experimental real-world data. Finally, we show that transfer learning enables the generation of high-affinity antibody sequences from low-N training data. Our work establishes a priori feasibility and the theoretical foundation of high-throughput ML-based mAb design.

• Bollineni, Ravi Chand; Tran, Trung; Lund-Johansen, Fridtjof & Olweus, Johanna (2022). Chasing neoantigens; invite naïve T cells to the party. Current Opinion in Immunology. ISSN 0952-7915. 75, p. 1–7. doi: 10.1016/j.coi.2022.102172. Full text in Research Archive
• Christensen, Ingrid Egeland; Jyssum, Ingrid; Tveter, Anne Therese; Sexton, Joseph; Tran, Trung & Mjaaland, Siri [Show all 19 contributors for this article] (2022). The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study. BMC Medicine. 20(1), p. 1–13. doi: 10.1186/s12916-022-02587-8. Full text in Research Archive Show summary

  Background The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. Methods IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6–48 days, second within 49–123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. Results A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn’s disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15–24] and 97 days [87–105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018–6068] in patients and 6187 BAU/ml [4105–7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58–1053] in patients and 1520 BAU/ml [979–3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was − 83% in patients and − 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls − 4.9 (95% CI − 7.4 to − 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. Conclusions Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

• Brunvoll, Sonja Hjellegjerde; Nygaard, Anders Benteson; Ellingjord-Dale, Merete; Holland, Petter; Istre, Mette Stausland & Kalleberg, Karl Trygve [Show all 15 contributors for this article] (2022). Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial. The BMJ. 378. doi: 10.1136/bmj-2022-071245. Full text in Research Archive Show summary

  Objective To determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in Norway. Design Quadruple blinded, randomised placebo controlled trial. Setting Norway, 10 November 2020 to 2 June 2021. Participants 34601 adults (aged 18-75 years), not taking daily vitamin D supplements. Intervention 5 mL/day of cod liver oil (10 µg of vitamin D, n=17278) or placebo (n=17323) for up to six months. Main outcome measures Four co-primary endpoints were predefined: the first was a positive SARS-CoV-2 test result determined by reverse transcriptase-quantitative polymerase chain reaction and the second was serious covid-19, defined as self-reported dyspnoea, admission to hospital, or death. Other acute respiratory infections were indicated by the third and fourth co-primary endpoints: a negative SARS-CoV-2 test result and self-reported symptoms. Side effects related to the supplementation were self-reported. The fallback method was used to handle multiple comparisons. Results Supplementation with cod liver oil was not associated with a reduced risk of any of the co-primary endpoints. Participants took the supplement (cod liver oil or placebo) for a median of 164 days, and 227 (1.31%) participants in the cod liver oil group and 228 (1.32%) participants in the placebo group had a positive SARS-CoV-2 test result (relative risk 1.00, multiple comparison adjusted confidence interval 0.82 to 1.22). Serious covid-19 was identified in 121 (0.70%) participants in the cod liver oil group and in 101 (0.58%) participants in the placebo group (1.20, 0.87 to 1.65). 8546 (49.46%) and 8565 (49.44%) participants in the cod liver oil and placebo groups, respectively, had ≥1 negative SARS-CoV-2 test results (1.00, 0.97 to 1.04). 3964 (22.94%) and 3834 (22.13%) participants in the cod liver oil and placebo groups, respectively, reported ≥1 acute respiratory infections (1.04, 0.97 to 1.11). Only low grade side effects were reported in the cod liver oil and placebo groups. Co nclusion Supplementation with cod liver oil in the winter did not reduce the incidence of SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections compared with placebo. Trial registration ClinicalTrials.gov NCT04609423.

• Tunheim, Gro; Rø, Gunnar Øyvind Isaksson; Chopra, Adity; Aase, Audun; Kran, Anne-Marte Bakken & Vaage, John T. [Show all 8 contributors for this article] (2022). Prevalence of antibodies against SARS-CoV-2 in the Norwegian population, August 2021. Influenza and Other Respiratory Viruses. ISSN 1750-2640. 16(6), p. 1004–1013. doi: 10.1111/irv.13024. Full text in Research Archive Show summary

  Background One year into the COVID-19 pandemic, the cumulative number of confirmed COVID-19 cases in Norway was still low. In January 2021, when the Norwegian COVID-19 vaccination campaign started, the national seroprevalence estimate of SARS-CoV-2 antibodies was 3.2%. We have conducted a nationwide cross-sectional study in August 2021 to investigate the overall prevalence of SARS-CoV-2 antibodies in Norway after 8 months of COVID-19 mass vaccination and a third wave of SARS-CoV-2 infection. Methods Residual sera were collected from laboratories across Norway in August 2021. In IgG antibodies against the spike protein, the spike receptor binding domain (RBD) and the nucleocapsid protein of SARS-CoV-2 were measured by a bead-based flow cytometric assay. Results In total, 1926 residual sera were collected from individuals aged 0–98 years; 55.1% were from women. The overall national estimated seroprevalence from vaccination and/or infection was 62.6% (credible interval [CrI] 60.1%–65.2%) based on having antibodies against both spike and RBD. Estimated seroprevalence increased with age. Among all samples, 11.7% had antibodies against nucleocapsid. For unvaccinated children <12 years, the seroprevalence estimate due to SARS-CoV-2 infection was 12.5% (95% CrI 9.3%–16.1%). Of seropositive samples from the unvaccinated children, 31.9% lacked anti-nucleocapsid antibodies. Conclusions The high overall SARS-CoV-2 seroprevalence estimates are in line with Norwegian registry data. Vaccination, not infection, contributed the most to the high seroprevalence in August 2021. Lack of antibodies against nucleocapsid should not automatically be interpreted as absence of previous infection as this could lead to underestimation of COVID-19 cases in seroprevalence studies.

• Jyssum, Ingrid; Kared, Hassen; Tran, Trung; Tveter, Anne Therese; Provan, Sella Aarrestad & Sexton, Joseph [Show all 22 contributors for this article] (2021). Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study. The Lancet Rheumatology. 00. doi: 10.1016/S2665-9913(21)00394-5. Full text in Research Archive Show summary

  Background In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. Methods This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2–4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7–10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. Findings Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222–324] in responders vs 107 days [80–152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. Interpretation This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6–9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response.

• Lerum, Tøri Vigeland; Maltzahn, Niklas; Aukrust, Pål; Trøseid, Marius; Nezvalova-Henriksen, Katerina & Kåsine, Trine [Show all 27 contributors for this article] (2021). Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9. Scientific Reports. 11, p. 1–12. doi: 10.1038/s41598-021-02547-x. Full text in Research Archive Show summary

  The association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.

• Kåsine, Trine; Riise, Anne Margarita Dyrhol; Barratt-Due, Andreas; Kildal, Anders Benjamin; Olsen, Inge Christoffer & Nezvalova-Henriksen, Katerina [Show all 39 contributors for this article] (2021). Neutrophil count predicts outcome in hospitalized COVID-19 patients. Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 291(2), p. 241–243. doi: 10.1111/joim.13377. Full text in Research Archive Show summary

  Despite numerous studies on SARS-CoV-2-induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure(RF). Few studies have evaluated the prognostic value of routine diagnostic repertoire available at most hospitals. The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial, evaluating hydroxychloroquine (HCQ)and remdesivir compared to standard of care in hospitalized COVID-19 patients [1]. We explored whether standard biomarkers in peripheral blood could give information on ICU admission and RFin hospitalized COVID-19 patients.

• Tunheim, Gro; Rø, Gunnar Øyvind Isaksson; Tran, Trung; Kran, Anne-Marte Bakken; Andersen, Jan Terje & Vaage, Eline Benno [Show all 10 contributors for this article] (2021). Trends in seroprevalence of SARS-CoV-2 and infection fatality rate in the Norwegian population through the first year of the COVID-19 pandemic. Influenza and Other Respiratory Viruses. ISSN 1750-2640. 16(2), p. 204–212. doi: 10.1111/irv.12932. Full text in Research Archive Show summary

  Background Infection with the novel coronavirus SARS-CoV-2 induces antibodies that can be used as a proxy for COVID-19. We present a repeated nationwide cross-sectional study assessing the seroprevalence of SARS-CoV-2, the infection fatality rate (IFR), and infection hospitalization rate (IHR) during the first year of the pandemic in Norway. Methods Residual serum samples were solicited in April/May 2020 (Round 1), in July/August 2020 (Round 2) and in January 2021 (Round 3). Antibodies against SARS-CoV-2 were measured using a flow cytometer-based assay. Aggregate data on confirmed cases, COVID-19-associated deaths and hospitalizations were obtained from the Emergency preparedness registry for COVID-19 (Beredt C19), and the seroprevalence estimates were used to estimate IFR and IHR. Results Antibodies against SARS-CoV-2 were measured in 4840 samples. The estimated seroprevalence increased from 0.8% (95% credible interval [CrI] 0.4%–1.3%) after the first wave of the pandemic (Rounds 1 and 2 combined) to 3.2% (95% CrI 2.3%–4.2%) (Round 3). The IFR and IHR were higher in the first wave than in the second wave and increased with age. The IFR was 0.2% (95% CrI 0.1%–0.3%), and IHR was 0.9% (95% CrI 0.6%–1.5%) for the second wave. Conclusions The seroprevalence estimates show a cumulative increase of SARS-CoV-2 infections over time in the Norwegian population and suggest some under-recording of confirmed cases. The IFR and IHR were low, corresponding to the relatively low number of COVID-19-associated deaths and hospitalizations in Norway. Most of the Norwegian population was still susceptible to SARS-CoV-2 infection after the first year of the pandemic.

• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Show all 22 contributors for this article] (2021). Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. doi: 10.1136/jnnp-2021-327612. Full text in Research Archive Show summary

  Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

• Martinez-Val, Ana; Bekker-Jensen, Dorte B.; Steigerwald, Sophia; Koenig, Claire; Østergaard, Ole & Mehta, Adi [Show all 18 contributors for this article] (2021). Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution. Nature Communications. 12(1), p. 1–17. doi: 10.1038/s41467-021-27398-y. Full text in Research Archive
• Lund-Johansen, Fridtjof; Tran, Trung & Mehta, Adi (2021). Towards reproducibility in large-scale analysis of protein–protein interactions. Nature Methods. ISSN 1548-7091. 18(7), p. 720–721. doi: 10.1038/s41592-021-01202-7. Full text in Research Archive
• Schultz, Nina Haagenrud; Sørvoll, Ingvild Hausberg; Michelsen, Annika; Munthe, Ludvig Andre; Lund-Johansen, Fridtjof & Ahlen, Maria Therese [Show all 11 contributors for this article] (2021). Thrombosis and thrombocytopenia after CHADOX1 NCoV-19 vaccination. New England Journal of Medicine. ISSN 0028-4793. 384(22), p. 2124–2130. doi: 10.1056/NEJMoa2104882. Full text in Research Archive Show summary

  We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4–polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

• Akbar, Rahmad; Robert, Philippe Paul Auguste; Pavlović, Milena; Jeliazkov, Jeliazko R.; Snapkov, Igor & Slabodkin, Andrei [Show all 15 contributors for this article] (2021). A compact vocabulary of paratope-epitope interactions enables predictability of antibody-antigen binding. Cell reports. 34:108856(11), p. 1–21. doi: 10.1016/j.celrep.2021.108856. Full text in Research Archive Show summary

  Antibody-antigen binding relies on the specific interaction of amino acids at the paratope-epitope interface. The predictability of antibody-antigen binding is a prerequisite for de novo antibody and (neo-)epitope design. A fundamental premise for the predictability of antibody-antigen binding is the existence of paratope- epitope interaction motifs that are universally shared among antibody-antigen structures. In a dataset of non-redundant antibody-antigen structures, we identify structural interaction motifs, which together compose a commonly shared structure-based vocabulary of paratope-epitope interactions. We show that this vocabulary enables the machine learnability of antibody-antigen binding on the paratope-epitope level using generative machine learning. The vocabulary (1) is compact, less than 104 motifs; (2) distinct from non-immune protein-protein interactions; and (3) mediates specific oligo- and polyreactive interactions between paratope-epitope pairs. Our work leverages combined structure- and sequence-based learning to demonstrate that machine-learning-driven predictive paratope and epitope engineering is feasible.

• Barratt-Due, Andreas; Olsen, Inge Christoffer; Nezvalova-Henriksen, Katerina; Kåsine, Trine; Lund-Johansen, Fridtjof & Hoel, Hedda Benedicte [Show all 43 contributors for this article] (2021). Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 : A Randomized Trial. Annals of Internal Medicine. ISSN 0003-4819. 174(9), p. 1261–1269. doi: 10.7326/M21-0653. Full text in Research Archive Show summary

  Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). Setting: 23 hospitals in Norway. Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. Limitation: The trial had no placebo group. Conclusion: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19.

• Helsingen, Lise Mørkved; Løberg, Magnus; Refsum, Erle; Gjøstein, Dagrun Kyte; Wieszczy, Paulina & Olsvik, Ørjan [Show all 16 contributors for this article] (2021). Covid-19 transmission in fitness centers in Norway - a randomized trial. BMC Public Health. 21, p. 1–9. doi: 10.1186/s12889-021-12073-0. Full text in Research Archive Show summary

  Background: Closed fitness centers during the Covid-19 pandemic may negatively impact health and wellbeing. We assessed whether training at fitness centers increases the risk of SARS-CoV-2 virus infection.<p> <p>Methods: In a two-group parallel randomized controlled trial, fitness center members aged 18 to 64 without Covid-19-relevant comorbidities, were randomized to access to training at a fitness center or no-access. Fitness centers applied physical distancing (1 m for floor exercise, 2 m for high-intensity classes) and enhanced hand and surface hygiene. Primary outcomes were SARS-CoV-2 RNA status by polymerase chain reaction (PCR) after 14 days, hospital admission after 21 days. The secondary endpoint was SARS-CoV-2 antibody status after 1 month.<p> <p>Results: 3764 individuals were randomized; 1896 to the training arm and 1868 to the no-training arm. In the training arm, 81.8% trained at least once, and 38.5% trained ≥six times. Of 3016 individuals who returned the SARSCoV-2 RNA tests (80.5%), there was one positive test in the training arm, and none in the no-training arm (risk difference 0.053%; 95% CI − 0.050 to 0.156%; p = 0.32). Eleven individuals in the training arm (0.8% of tested) and 27 in the no-training arm (2.4% of tested) tested positive for SARS-CoV-2 antibodies (risk difference − 0.87%; 95%CI − 1.52% to − 0.23%; p = 0.001). No outpatient visits or hospital admissions due to Covid-19 occurred in either arm.<p> <p>Conclusion: Provided good hygiene and physical distancing measures and low population prevalence of SARS-CoV-2 infection, there was no increased infection risk of SARS-CoV-2 in fitness centers in Oslo, Norway for individuals without Covid-19-relevant comorbidities.

• Voskuil, Jan L.A.; Bandrowski, Anita; Begley, C. Glenn; Bradbury, Andrew R.M.; Chalmers, Andrew D. & Gomes, Aldrin V. [Show all 15 contributors for this article] (2020). The Antibody Society’s antibody validation webinar series. mAbs. ISSN 1942-0862. 12:e1794421(1), p. 1–10. doi: 10.1080/19420862.2020.1794421. Full text in Research Archive
• Holter, Jan Cato; Pischke, Soeren; Boer, Eline de; Lind, Andreas; Jenum, Synne & Holten, Aleksander Rygh [Show all 32 contributors for this article] (2020). Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 117(40), p. 25018–25025. doi: 10.1073/pnas.2010540117. Full text in Research Archive Show summary

  Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.

• Rosa-Carrillo, Daniel de la; Sikorski, Krzysztof; Khnykin, Denis; Wu, Weiwei & Lund-Johansen, Fridtjof (2018). High-resolution antibody array analysis of proteins from primary human keratinocytes and leukocytes. PLOS ONE. 13: e0209271(12). doi: 10.1371/journal.pone.0209271. Full text in Research Archive Show summary

  Antibody array analysis of labeled proteomes has high throughput and is simple to perform, but validation remains challenging. Here, we used differential detergent fractionation and size exclusion chromatography in sequence for high-resolution separation of biotinylated proteins from human primary keratinocytes and leukocytes. Ninety-six sample fractions from each cell type were analyzed with microsphere-based antibody arrays and flow cytometry (microsphere affinity proteomics; MAP). Monomeric proteins and multi-molecular complexes in the cytosol, cytoplasmic organelles, membranes and nuclei were resolved as discrete peaks of antibody reactivity across the fractions. The fractionation also provided a two-dimensional matrix for assessment of specificity. Thus, antibody reactivity peaks were considered to represent specific binding if the position in the matrix was in agreement with published information about i) subcellular location, ii) size of the intended target, and iii) cell type-dependent variation in protein expression. Similarities in the reactivity patterns of either different antibodies to the same protein or antibodies to similar proteins were used as additional supporting evidence. This approach provided validation of several hundred proteins and identification of monomeric proteins and protein complexes. High-resolution MAP solves many of the problems associated with obtaining specificity with immobilized antibodies and a protein label. Thus, laboratories with access to chromatography and flow cytometry can perform large-scale protein analysis on a daily basis. This opens new possibilities for cell biology research in dermatology and validation of antibodies.

• Sikorski, Krzysztof; Mehta, Adi; Inngjerdingen, Marit; Thakor, Flourina Kumar; Kling, Simon & Kalina, Tomas [Show all 14 contributors for this article] (2018). A high-throughput pipeline for validation of antibodies. Nature Methods. ISSN 1548-7091. 15(11), p. 909–912. doi: 10.1038/s41592-018-0179-8. Full text in Research Archive Show summary

  Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we used preparative gel electrophoresis to develop a capture format for WB. Fractions with soluble, size-separated proteins facilitated parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). This pipeline provided the means for large-scale implementation of antibody validation concepts proposed by an international working group on antibody validation (IWGAV).Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we used preparative gel electrophoresis to develop a capture format for WB. Fractions with soluble, size-separated proteins facilitated parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). This pipeline provided the means for large-scale implementation of antibody validation concepts proposed by an international working group on antibody validation (IWGAV).

• Vesterhus, Mette; Holm, Anders; Hov, Johannes Espolin Roksund; Nygård, Ståle; Schrumpf, Erik & Melum, Espen [Show all 23 contributors for this article] (2017). Novel serum and bile protein markers predict primary sclerosing cholangitis disease severity and prognosis. Journal of Hepatology. ISSN 0168-8278. 66(6), p. 1214–1222. doi: 10.1016/j.jhep.2017.01.019. Full text in Research Archive Show summary

  Background & Aims Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We aimed to identify novel protein biomarkers of disease severity and prognosis in primary sclerosing cholangitis (PSC). Methods Using a bead-based array targeting 63 proteins, we profiled a derivation panel of Norwegian endoscopic retrograde cholangiography bile samples (55 PSC, 20 disease controls) and a Finnish validation panel (34 PSC, 10 disease controls). Selected identified proteins were measured in serum from two Norwegian PSC cohorts (n = 167 [1992–2006] and n = 138 [2008–2012]), inflammatory bowel disease (n = 96) and healthy controls (n = 100). Results In the bile derivation panel, the levels of 14 proteins were different between PSC patients and controls (p <0.05); all were confirmed in the validation panel. Twenty-four proteins in the bile derivation panel were significantly (p <0.05) different between PSC patients with mild compared to severe cholangiographic changes (modified Amsterdam criteria); this was replicated for 18 proteins in the validation panel. Interleukin (IL)-8, matrix metallopeptidase (MMP)9/lipocalin (LCN)2-complex, S100A8/9, S100A12 and tryptophan hydroxylase (TPH)2 in the bile were associated with both a PSC diagnosis and grade of cholangiographic changes. Stratifying PSC patients according to tertiles of serum IL-8, but not MMP9/LCN2 and S100A12, provided excellent discrimination for transplant-free survival both in the serum derivation and validation cohort. Furthermore, IL-8 was associated with transplant-free survival in multivariable analyses in both serum panels independently of age and disease duration, indicating an independent influence on PSC progression. However, the Enhanced Liver Fibrosis (ELF®) test and Mayo risk score proved to be stronger predictors of transplant-free survival. Conclusions Based on assaying of biliary proteins, we have identified novel biliary and serum biomarkers as indicators of severity and prognosis in PSC. Lay summary Prognostic biomarkers are lacking in primary sclerosing cholangitis, hampering patient care and the development of therapy. We have identified inflammatory proteins including calprotectin and IL-8 as important indicators of disease severity and prognosis in bile and serum from patients with primary sclerosing cholangitis.

• Kanderova, Veronika; Kuzilkova, Daniela; Stuchly, Jan; Vaskova, Martina; Brdicka, Tomas & Fišer, Karel [Show all 9 contributors for this article] (2016). High-resolution Antibody Array Analysis of Childhood Acute Leukemia Cells. Molecular & Cellular Proteomics. ISSN 1535-9476. doi: 10.1074/mcp.M115.054593. Full text in Research Archive
• Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry & Reichert, Janice M. [Show all 10 contributors for this article] (2016). Antibody engineering &amp; therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA. mAbs. ISSN 1942-0862. 8(3), p. 617–652. doi: 10.1080/19420862.2016.1153211. Full text in Research Archive
• Lund-Johansen, Fridtjof; Rosa-Carrillo, Daniel de la; Mehta, Adi; Sikorski, Krzysztof; Inngjerdingen, Marit & Kalina, Tomáš [Show all 11 contributors for this article] (2016). MetaMass, a tool for meta-analysis of subcellular proteomics data. Nature Methods. ISSN 1548-7091. 13(10), p. 837–840. doi: 10.1038/nmeth.3967. Full text in Research Archive
• Strønen, Erlend; Toebes, Mireille; Kelderman, Sander; Buuren, Marit M. van; Yang, Weiwen & Rooij, Nienke Van [Show all 11 contributors for this article] (2016). Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science. ISSN 0036-8075. 352(6291), p. 1337–1341. doi: 10.1126/science.aaf2288. Full text in Research Archive
• Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao & Gräslund, Susanne [Show all 13 contributors for this article] (2015). Recombinant renewable polyclonal antibodies. mAbs. ISSN 1942-0862. 7(1), p. 32–41. doi: 10.4161/19420862.2015.989047. Full text in Research Archive Show summary

  Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be ampli fied over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective ampli fi cation of antibodies directed toward desirable target speci fi c epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without signi fi cant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

• Vesterhus, Mette; Hov, Johannes Espolin Roksund; Holm, Anders; Schrumpf, Erik; Nygård, Ståle & Godang, Kristin [Show all 25 contributors for this article] (2015). Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis. Hepatology. ISSN 0270-9139. 62(1), p. 188–197. doi: 10.1002/hep.27825. Full text in Research Archive
• Almagro, Juan Carlos; Gilliland, Gary L.; Breden, Felix; Scott, Jamie K.; Sok, Devin & Pauthner, Matthias [Show all 24 contributors for this article] (2014). Antibody engineering & therapeutics, the annual meeting of The Antibody Society. mAbs. ISSN 1942-0862. 6(3), p. 577–618. doi: 10.4161/mabs.28421. Full text in Research Archive
• Kumari, Shraddha; Waelchli, Sebastien; Fallang, Lars-Egil; Yang, Weiwen; Lund-Johansen, Fridtjof & Schumacher, Ton N. [Show all 7 contributors for this article] (2014). Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 111(1), p. 403–408. doi: 10.1073/pnas.1306549111. Full text in Research Archive

View all works in NVA

• Palashati, Heyilimu; Flem-Karlsen, Karine; Heinzelbecker, Julia; Eggebø, Maria Stadheim; Chandler, Nicholas John & Yang, W [Show all 10 contributors for this article] (2026). P02.12 Identification of an HLA-A*11:01-restricted KRASG12V-specific T cell receptor with strong antitumor responses in patient-derived cancer models. Journal for ImmunoTherapy of Cancer (JITC). 14(Suppl 1). doi: 10.1136/jitc-2026-itoc.26. Full text in Research Archive
• Skjellegrind, Håvard Kjesbu; Kelsey, Pieta Tasnim; Wolford, Brooke N.; Lund-Johansen, Fridtjof; Selbæk, Geir & Allore, Heather (2025). Infection antibodies associated with Alzheimer’s dementia - The Norwegian HUNT Study. Full text in Research Archive
• Olweus, Johanna & Lund-Johansen, Fridtjof (2025). T cells engineered to target a shared β-catenin mutation eradicate solid tumors in mice. Nature Immunology. ISSN 1529-2908. doi: 10.1038/s41590-025-02287-4. Full text in Research Archive
• Lund-Johansen, Fridtjof (2024). How should we validate affinity proteomics? Full text in Research Archive
• Lund-Johansen, Fridtjof (2024). Finding TCR targets by immunopeptidomics. Full text in Research Archive
• Lund-Johansen, Fridtjof (2023). Antibody Specificity: A strong case for third-party testing. eLIFE. 12. doi: 10.7554/eLife.93329. Full text in Research Archive
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Full text in Research Archive
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Full text in Research Archive
• Anthi, Aina Karen; Kolderup, Heidi Anette; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa & Tjärnhage, Elias [Show all 30 contributors for this article] (2023). A novel non-invasive FcRn-targeted mucosal vaccine strategy. Full text in Research Archive
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. 8(1). doi: 10.1038/s41541-023-00600-6. Full text in Research Archive
• Anthi, Aina Karen; Vaage, Eline Benno; Bern, Malin C.; Benjakul, Sopisa; Tjärnhage, Elias & Lode, Heidrun Elisabeth [Show all 29 contributors for this article] (2023). A non-invasive subunit vaccine technology targeting FcRn induces protective mucosal and systemic antibody immunity in mouse models. Full text in Research Archive
• Lund-Johansen, Fridtjof (2023). Assessing specificity of the Somascan serum proteomics platform. Full text in Research Archive
• Rasmussen, Tilde; König, Marton; Lorentzen, Åslaug Rudjord; Schikora-Rustad, Stine; Berge, Tone & Holmøy, Trygve [Show all 17 contributors for this article] (2022). Safety of a third SARS CoV 2 mRNA vaccine dose in people with multiple sclerosis. Full text in Research Archive
• König, Marton; Wolf, Asia-Sophia Fumika Michaela; Ravussin, Anthony; Chopra, Adity; Tran, Trung & Torgauten, Hilde Marie [Show all 28 contributors for this article] (2022). Immunogenicity and efficacy of mRNA-COVID-19 vaccines in people with multiple sclerosis. Full text in Research Archive
• Midtvedt, Karsten; Vaage, John T.; Heldal, Kristian; Munthe, Ludvig Andre; Lund-Johansen, Fridtjof & Åsberg, Anders (2022). Fourth dose of the SARS-CoV-2 vaccine in kidney transplant recipients with previously impaired humoral antibody response. American Journal of Transplantation. ISSN 1600-6135. doi: 10.1111/ajt.17091. Full text in Research Archive
• Midtvedt, Karsten; Tran, Trung; Parker, Krystina; Marti, Hans Peter; Stenehjem, Aud Eldrid & Gøransson, Lasse Gunnar [Show all 12 contributors for this article] (2021). Low Immunization Rate in Kidney Transplant Recipients Also After Dose 2 of the BNT162b2 Vaccine: Continue to Keep Your Guard up! Transplantation. ISSN 0041-1337. 105(8), p. E80–E81. doi: 10.1097/TP.0000000000003856. Full text in Research Archive
• König, Marton; Lorentzen, Åslaug Rudjord; Torgauten, Hilde Marie; Tran, The Trung; Schikora-Rustad, Stine & Vaage, Eline Benno [Show all 22 contributors for this article] (2021). Humoral Immunity to SARS-CoV-2 mRNA Vaccination in People with Multiple Sclerosis using High-Efficacy Disease Modifying Therapies. Full text in Research Archive
• Olweus, Johanna & Lund-Johansen, Fridtjof (2019). Finding Neo (antigens, that is). Blood. ISSN 0006-4971. 134(2), p. 108–109. doi: 10.1182/blood.2019001334. Full text in Research Archive
• Lund-Johansen, Fridtjof & Browning, Michael D. (2017). Should we ignore western blots when selecting antibodies for other applications? Nature Methods. ISSN 1548-7091. 14(3), p. 215–215. doi: 10.1038/nmeth.4192. Full text in Research Archive
• Freedman, Leonard P.; Gibson, Mark C.; Bradbury, Andrew R.M.; Buchberg, Arthur M.; Davis, Darryl & Dolled-Filhart, Marisa P. [Show all 8 contributors for this article] (2016). The need for improved education and training in research antibody usage and validation practices. BioTechniques. ISSN 0736-6205. 61(1), p. 16–18. doi: 10.2144/000114431. Full text in Research Archive
• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Hungnes, Olav; Lund-Johansen, Fridtjof & Vaage, Eline Benno [Show all 9 contributors for this article] (2021). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in January 2021. Norwegian Institute of Public Health, Division of Infection Control and Environmental Health. ISSN 9788284061825. Full text in Research Archive Show summary

  Norsk sammendrag Covid-19 er en infeksjonssykdom som skyldes det nye koronaviruset SARS-CoV-2. Infeksjon med SARS-CoV-2 induserer antistoffer mot viruset, og funn av virusspesifikke antistoffer i blodprøver fra uvaksinerte indikerer gjennomgått infeksjon. Dette er den tredje studien som måler antistoffer mot SARS-CoV-2 i serumprøver som er systematisk samlet inn fra ulike geografiske områder i Norge, og som representerer alle aldersgrupper. Den første studien, basert på restsera samlet inn i april/mai 2020 og august 2019, ble publisert som en rapport i juni 2020 (1). Den andre studien, basert på restsera samlet inn på sensommeren 2020, ble publisert som en rapport i desember 2020 (2). I denne studien, ble til sammen 1912 restsera samlet inn i løpet av januar 2021 (uke 53-6) fra 17 laboratorier. De fleste prøvene (85,7 %) ble samlet inn mellom uke 1-3. Serumprøvene ble testet for antistoffer mot SARS-CoV-2 med en metode som er utviklet og etablert ved Avdeling for immunologi og transfusjonsmedisin ved Oslo universitetssykehus. Ut ifra disse målingene lå den estimerte andelen av den norske befolkningen som har antistoffer mot SARS-CoV-2 (seroprevalensen) på 3,2 % (95 % kredibilitetsintervall 2,3 – 4,1) i denne perioden. Dette er høyere enn den estimerte seroprevalensen sensommeren 2020 (0,6 % (95 % kredibilitetsintervall 0,2 – 1,2)) (2). Antistoffer mot SARS-CoV-2 ble funnet i totalt 61 prøver. De positive prøvene var fra personer bosatt i 10 av de 11 norske fylkene, men det var ingen signifikante forskjeller i estimert seroprevalens mellom de ulike fylkene. Imidlertid var det stor variasjon i antall prøver fra hvert fylke. Det ble ikke funnet noen signifikante forskjeller i estimert seroprevalens mellom ulike aldersgrupper eller mellom ulike kjønn.

• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Hungnes, Olav; Lund-Johansen, Fridtjof & Tran, Trung [Show all 8 contributors for this article] (2020). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in late summer 2020. Folkehelseinstituttet. ISSN 9788284061559. Full text in Research Archive Show summary

  COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Infection with SARS-CoV-2 induces antibodies to the virus, therefore the presence of these antibodies in a person’s blood indicates that the person has been infected with SARS-CoV-2. This is the second study measuring antibodies against SARS-CoV-2 in residual serum samples collected systematically from various geographical regions in Norway and covering all age groups. The first study with residual sera from April/May 2020 and August 2019, was published as a report in June 2020 (1). In the present study, a total of 1812 residual sera were sampled from 16 microbiology laboratories from late July to mid-September 2020 (week numbers 30-37). The sera were tested for antibodies against SARS-CoV-2 using a novel in-house assay established at the Department of Immunology, Oslo University Hospital. Based on these measurements, the estimated seroprevalence in the Norwegian population in the late summer was 0.6% [95% credible interval (CrI) 0.2 - 1.2]. This is not significantly different from the seroprevalence estimate based on the 900 samples collected in the spring (1.0% [95% CrI 0.1- 2.4])(1). Antibodies against SARS-CoV-2 were found in samples from 6 of the 11 counties, but there were no significant differences between the seroprevalence estimates for each county. However, the sample size from each county varied considerably (from 20 to 387) and the number of positive samples were limited (11 in total). There were no significant differences between the seroprevalence estimates for the various age groups or between males and females. During the summer of 2020, the pandemic was quite contained in Norway. This may explain why the estimated seroprevalence for the Norwegian population was similar in the spring and in the late summer. In this first follow-up study, more laboratories contributed, and a greater number of samples was tested, leading to better precision of the seroprevalence estimate. New follow-up studies of antibodies against SARS-CoV-2 in future collections of residual sera will provide further information about the development of the COVID-19 pandemic in Norway

• Tunheim, Gro; Kran, Anne-Marte Bakken; Rø, Gunnar Øyvind Isaksson; Steens, Anneke; Hungnes, Olav & Lund-Johansen, Fridtjof [Show all 9 contributors for this article] (2020). Seroprevalence of SARS-CoV-2 in the Norwegian population measured in residual sera collected in April/May 2020 and August 2019. Folkehelseinstituttet. ISSN 9788284061092. Full text in Research Archive Show summary

  COVID-19 is an infectious disease caused by the novel coronavirus SARS-CoV-2. Infection with SARS-CoV-2 induces antibodies to the virus, therefore the presence of these antibodies in a person’s blood indicates that the person has been infected with SARS-CoV-2. This is the first study measuring antibodies against SARS-CoV-2 in serum samples collected systematically from various geographical regions in Norway and covering all age groups. A total of 900 residual sera from nine laboratories were sampled in week numbers 17-20, 2020, and tested for antibodies against SARS-CoV-2 using a novel in-house assay established at the Department of Immunology, Oslo University Hospital. Based on these measurements, the estimated seroprevalence in the Norwegian population is probably close to 1% (1.0% (95% credible interval 0.1% - 2.4%)). We did not find any differences in seroprevalence by gender or age group. However, there seem to be geographical differences in the prevalence of seropositive individuals; there was a non-significant trend indicating that the number of positive samples and the estimated seroprevalence was higher in Oslo than in other regions. However, the sample size was limited as not all counties were included, and only an average number of 100 samples have been collected from each laboratory. Therefore, these results should be interpreted with caution. Follow-up studies of antibodies against SARS-CoV-2 in future collections of residual sera can provide further information about the development of the COVID-19 pandemic in Norway.

View all works in NVA