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

To protect healthcare workforce during the COVID-19 pandemic, rigorous efforts were made to reduce infection rates among healthcare workers (HCWs), especially prior to vaccine availability. This study aimed to investigate the prevalence of SARS-CoV-2 infections among HCWs and identify potential risk factors associated with transmission. We searched MEDLINE, Embase, and Google Scholar from 1 December 2019 to 5 February 2024. From 498 initial records, 190 articles were reviewed, and 63 studies were eligible. ROBINS-E tool revealed a lower risk of bias in several domains; however, some concerns related to confounding and exposure measurement were identified. Globally, 11% (95% confidence interval (CI) 9–13) of 283,932 HCWs were infected with SARS-CoV-2. Infection rates were associated with a constellation of risk factors and major circulating SARS-CoV-2 variants. Household exposure (odds ratio (OR) 7.07; 95% CI 3.93–12.73), working as a cleaner (OR 2.72; 95% CI 1.39–5.32), occupational exposure (OR 1.79; 95% CI 1.49–2.14), inadequate training on infection prevention and control (OR 1.46; 95% CI 1.14–1.87), insufficient use of personal protective equipment (OR 1.45; 95% CI 1.14–1.84), performing aerosol generating procedures (OR 1.36; 95% CI 1.21–1.52) and inadequate hand hygiene (OR 1.17; 95% CI 0.79–1.73) were associated with an increased SARS-CoV-2 infection. Conversely, history of quarantine (OR 0.23; 95% CI 0.08–0.60) and frequent decontamination of high touch areas (OR 0.52; 95% CI 0.42–0.64) were protective factors against SARS-CoV-2 infection. This study quantifies the substantial global burden of SARS-CoV-2 infection among HCWs. We underscore the urgent need for effective infection prevention and control measures, particularly addressing factors such as household exposure and occupational practices by HCWs, including cleaning staff.

Complex respiratory models, including air-liquid interface (ALI) transwell cultures and airway organoids, have emerged as promising tools for studying human respiratory virus infections. These models address several limitations of conventional two-dimensional cell line and animal models. However, the lack of standardized protocols for the application of these models in infection studies limits the possibilities for comparing results across different research groups. Therefore, we applied a collaborative approach to harmonize several aspects of experimental methodology between different research laboratories, aiming to assess the comparability of different models of human airway epithelium in the context of respiratory viral infections. In this study, we compared three different models of human respiratory epithelium: a primary human bronchial epithelial cell-derived ALI transwell model, and two airway organoid models established from human airway- and lung-derived adult stem cells. We first assessed the presence of various differentiated cell types using immunofluorescence microscopy. Using a shared stock of influenza A virus, we then assessed viral growth kinetics, epithelial cytokine responses, and serum-mediated inhibition of infection. The presence of club, goblet, and ciliated cells was confirmed in all models. We observed similar viral replication kinetics with a >4-log increase in virus titre across all models using a TCID50 assay. Following infection, a reproducible antiviral cytokine response, including a consistent increase in CXCL10, IL-6, IFN-λ1, IFN-λ2/3, and IFN-β, was detected across all models. Finally, neutralization was assessed by pre-incubation of virus with human serum. Reduced viral replication was observed across all models, resulting in a 3- to 6-log decrease in virus titres as quantified by TCID50. In conclusion, all three models produced consistent results regardless of the varying cell sources, culturing approaches, and infection methods. Our collaborative efforts to harmonize infection experiments and compare ALI transwell and airway organoid models described here aid in advancing our understanding and improving the standardization of these complex respiratory models for future studies.

BackgroundPsoriasis is a chronic immune-mediated skin disease with systemic inflammation and comorbidities. Although the disease severity may vary over time, many patients suffer from mild to moderate disease. Often local treatment will be sufficient to control the symptoms, but they may have several side effects. ω-3 polyunsaturated fatty acids have shown promising results in clinical trials with mild-to-moderate psoriasis.MethodsWe explored the impact of phospholipid bound docosahexaenoic acid and eicosapentaenoic acid in a 3:1 ratio on immune cells and cytokine networks in peripheral blood of patients with psoriasis. We investigated the inter-relation of plasma cytokine levels and disease severity in 58 patients, and explored the status of circulating immune cell activity in 18 patients with non-severe psoriasis before and during herring roe oil supplementation. Plasma concentration of 22 cytokines was measured by Luminex technology and circulating immune cells were analyzed by multicolor flow cytometry.ResultsCCL2 levels decreased over time, and IFN-γR1 increased, possibly related to the action of ω-3 polyunsaturated fatty acids. We observed a shift from naïve to effector CD4+ T cells and decreases of CD38 expression on CD4+ and CD8+ T cells, CD56bright NK cells and CD14+CD16- classical monocytes.ConclusionsThese findings support the beneficial effect of herring roe oil supplementation.

Background: Persistent fever after SARS-CoV-2 infection in rituximab-treated patients has been reported. Due to reduced sensitivity in conventional sampling methods and unspecific symptoms in these patients, distinguishing between low-grade viral replication or hyperinflammation is challenging. Antiviral treatment is recommended as prophylactic or early treatment in the at-risk population; however, no defined treatment approaches for protracted SARS-CoV-2 infection exist. Results: We present a case of 96 days of persistent fever and SARS-CoV-2 infection in a patient receiving B cell depletion therapy for multiple sclerosis. Migratory lung infiltrates and positive PCR tests from serum (day-58 post infection) and lower airways (day-90 post infection) confirmed continuous viral replication. The dominant symptoms were continuous high fever, dyspnea and mild to moderate hypoxemia, which never developed into severe respiratory failure. The patient was hospitalized three times, with transient improvement after late antiviral treatment and full recovery 6 months post-rituximab infusion. Conclusions: A strategy for securing samples from lower airways and serum should be a prioritization to strengthen diagnostic certainty in immunocompromised patients. B-cell-deprived patients could benefit from late treatment with SARS-CoV-2-specific monoclonal antibodies and antivirals. Importantly, increased intervals between immunosuppressive therapy should be considered where feasible.

CD8+ T cells targeting 21-hydroxylase (21OH) are presumed to play a central role in the destruction of adrenocortical cells in autoimmune Addison's disease (AAD). Earlier reports have suggested two immunodominant CD8+ T cell epitopes within 21OH: LLNATIAEV (21OH ), restricted by HLA-A2, and EPLARLEL (21OH ), restricted by HLA-B8. We aimed to characterize polyclonal CD8+ T cell responses to the proposed epitopes in a larger patient cohort with AAD. Recombinant fluorescent HLA-peptide multimer reagents were used to quantify antigen-specific CD8+ T cells by flow cytometry. Interferon-gamma (IFNγ) Elispot and biochemical assays were used to functionally investigate the 21OH-specific T cells, and to map the exactly defined epitopes of 21OH. We found a significantly higher frequency of HLA-A2 restricted LLNATIAEV-specific cells in patients with AAD than in controls. These cells could also be expanded in an antigen specific manner and displayed a robust antigen-specific IFNγ production. In contrast, only negligible frequencies of EPLARLEL-specific T cells were detected in both patients and controls with limited IFNγ response. However, significant IFNγ production was observed in response to a longer peptide encompassing EPLARLEL, 21OH , suggesting alternative dominant epitopes. Accordingly, we discovered that the slightly offset ARLELFVVL (21OH ) peptide is a novel dominant epitope restricted by HLA-C7 and not by HLA-B8 as initially postulated. We have identified two dominant 21OH epitopes targeted by CD8+ T cells in AAD, restricted by HLA-A2 and HLA-C7, respectively. To our knowledge, this is the first HLA-C7 restricted epitope described for an autoimmune disease.

History of influenza A/H3N2 exposure, especially childhood infection, shape antibody responses after influenza vaccination and infection, but have not been extensively studied. We investigated the breadth and durability of influenza A/H3N2-specific hemagglutinin-inhibition antibodies after live-attenuated influenza vaccine in children (aged 3-17 years, n = 42), and after inactivated influenza vaccine or infection in adults (aged 22-61 years, n = 42) using 14 antigenically distinct A/H3N2 viruses circulating from 1968 to 2018. We found that vaccination and infection elicited cross-reactive antibody responses, predominantly directed against newer or future strains. Childhood H3-priming increased the breadth and magnitude of back-boosted A/H3N2-specific antibodies in adults. Broader and more durable A/H3N2-specific antibodies were observed in repeatedly vaccinated adults than in children and previously unvaccinated adults. Our findings suggest that early A/H3N2 exposure and frequent seasonal vaccination could increase the breadth and seropositivity of antibody responses, which may improve vaccine protection against future viruses.

Background Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. Methods Firstly, we developed a receptor-binding domain-specific haemagglutination test (HAT) to Wuhan and VOC (alpha, beta, gamma and delta) and compared to pseudotype, microneutralisation and virus neutralisation assays in 835 convalescent sera. Secondly, we investigated the antibody response using the HAT after two doses of mRNA (BNT162b2) vaccination. Sera were collected at baseline, three weeks after the first and second vaccinations from older (80–99 years, n  = 89) and younger adults (23–77 years, n  = 310) and compared to convalescent sera from naturally infected individuals (1–89 years, n  = 307). Results Here we show that HAT antibodies highly correlated with neutralising antibodies (R = 0.72–0.88) in convalescent sera. Home-dwelling older individuals have significantly lower antibodies to the Wuhan strain after one and two doses of BNT162b2 vaccine than younger adult vaccinees and naturally infected individuals. Moverover, a second vaccine dose boosts and broadens the antibody repertoire to VOC in naïve, not previously infected older and younger adults. Most (72–76%) older adults respond after two vaccinations to alpha and delta, but only 58–62% to beta and gamma, compared to 96–97% of younger vaccinees and 68–76% of infected individuals. Previously infected older individuals have, similarly to younger adults, high antibody titres after one vaccination. Conclusions Overall, HAT provides a surrogate marker for neutralising antibodies, which can be used as a simple inexpensive, rapid test. HAT can be rapidly adaptable to emerging VOC for large-scale evaluation of potentially decreasing vaccine effectiveness. Plain language summary The aim of this study was to rapidly investigate the immune responses after SARS-CoV-2 infection and vaccination of younger adults and the elderly. Antibodies are proteins produced by the immune system that are released into the bloodstream and help fight infections. A simple method using red blood cells obtained from blood was developed and used to detect antibodies to SARS-CoV-2. This test was able to measure protective antibodies to several variants of concern. The elderly had lower antibody responses after vaccination. Two vaccinations induced a broader antibody response to viral variants, similar to the response induced following Covid-19. This antibody detection method could be used as a finger prick test to rapidly detect specific antibodies to emerging variants and enable quick identification of individuals who might benefit from a booster vaccination. Ertesvåg, Xiao et al. describe a method to evaluate neutralising antibodies to SARS-CoV-2 infection or vaccination, including variants of concern. A second mRNA-vaccine dose results in a broader antibody repertoire in adults, although with reduced cross-reactivity to beta and gamma compared to alpha and delta, particularly in the elderly.

Background Emerging viral threats such as coronavirus, influenza, Lassa fever, Mpox, and Nipah virus continue to pose significant global health challenges. The development and deployment of effective vaccines are essential for outbreak control and pandemic preparedness. This protocol describes a systematic review that will synthesize evidence on vaccine candidates targeting high-priority viral threats and major vaccine platforms. Methods We will include randomised controlled trials (RCTs) assessing vaccine candidates for specified viruses (coronavirus, Lassa fever, Nipah virus, and Mpox) and platforms (protein-based, viral vector, and RNA) in the human populations. To encompass the full vaccine development landscape, exploratory and preclinical studies may also be included (any type of original research). Data sources will include MEDLINE Ovid, Embase Ovid (including ClinicalTrials.gov), and Cochrane Library (including CENTRAL), and grey literature (including conference proceedings, dissertations, trial registries, and company websites). Risk of bias will be assessed using Cochrane revised tool for assessing risk of bias in randomised trials (RoB-2) and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), and certainty of evidence will be evaluated using Grading of Recommendations Assessment, Development and Evaluation (GRADE). The primary outcomes are safety, immunogenicity, and vaccine efficacy or effectiveness, prioritised for their critical role in outbreak management and in guiding regulatory approval, public health policy, and clinical decision-making. Meta-analyses will be conducted where appropriate, using both fixed- and random-effects models. Subgroup analyses will be performed to explore heterogeneity based on virus type, vaccine platform, and outcome measures, where appropriate. Discussion This review will provide a comprehensive synthesis of vaccine development efforts across multiple platforms and pathogens with epidemic or pandemic potential. It will inform future research, policy, and investment decisions in global health preparedness. Systematic review registration PROSPERO 2025 CRD420251082338 on 6 October 2025.