Rebecca J Cox

• B.Sc. PhD
• Professor of Medical Virology and Head of Influenza Centre at University of Bergen

Aims The COVID-19 pandemic provided a unique opportunity to assess how infected patients viewed risk. We investigated whether cases infected early in the pandemic had assessed the risk to be lower, been more exposed and took fewer precautions to prevent infection. Methods We asked first-wave Norwegian COVID-19 patients ( n = 88) to recall how they...

Introduction Complex in vitro 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 proto...

Here, we present Link-Seq, a highly efficient droplet microfluidic method for combined sequencing of antibody encoding genes and the transcriptome of individual B-cells at large scale. The method is based on 3’-barcoding of the transcriptome and subsequent single molecule PCR in droplets, which freely shift the barcode along specific gene regions,...

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit‐for‐purpose chal...

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit‐for‐purpose chal...

Background This report summarizes the discussions and conclusions from the “Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID‐19 Pandemic” meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023. Conclusions Discussions around influenza virus correlates of protection and their u...

Introduction A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection. Methods Adults in a prospective cohort provided blood samples at day 0,...

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...

Long COVID is a complex condition where symptoms persist for more than 3 months after SARS-CoV-2 infection and affects an estimated 5-30% of individuals. While the pathobiology of long COVID is still evolving, persistent inflammation has emerged as an important feature of this condition. However, it is unclear if immune responses from COVID-19 vacc...

Objectives Booster COVID-19 vaccinations are used to protect the elderly, a group vulnerable to severe disease. We compared humoral and cellular immunity in older versus younger adults up to eight months after administering a BNT16b2 booster vaccine dose. Next, we analyzed the plasma levels of soluble T cell activation/exhaustion markers. Methods...

Live attenuated influenza vaccines (LAIV) typically induce a poor hemagglutination inhibition (HI) response, which is the standard correlate of protection for inactivated influenza vaccines. The significance of the HI response is complicated because the LAIV vaccine primarily induces the local mucosal immune system, while the HI assay measures the...

Background: This report summarizes the discussions and conclusions from the “Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic” meeting which took place in Seattle, USA, from March 1, 2023, to March 3, 2023. Conclusions: Discussions around influenza virus correlates of protection and their u...

Mucosal immunity is important in protecting from upper respiratory tract influenza infection. Human challenge provides a unique model to define correlates of protection with baseline immune responses being correlated to the quantity and length of viral shedding and clinical outcomes. Here, we discuss recent work on mucosal and systemic correlates o...

Public health strategies to protect against pandemics rely on members of the public volunteering to be tested when they have legitimate concerns about being infected. People may be motivated to seek testing due to believing they have been more at risk for infection, they have been more exposed to infection, or they have not taken the same precautio...

Introduction A substantial proportion of the over 700 million COVID-19 cases world-wide experience long-term symptoms. The objectives of this study were to compare symptom trajectories and risk factors for post-COVID-19 condition after Delta and Omicron infection. Methods This study consecutively recruited patients with SARS-CoV-2 infection from N...

The endemic human coronaviruses (HCoVs) circulate worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses...

Within the Innovative Health Initiative (IHI) Inno4Vac CHIMICHURRI project, a regulatory workshop was organised on the development and manufacture of challenge agent strains for Controlled Human Infection Model (CHIM) studies. Developers are often uncertain about which GMP requirements or regulatory guidelines apply but should be guided by the 2022...

Introduction The World Health Organization (WHO)'s Research and Development (R&D) Blueprint for Action to Prevent Epidemics, a plan of action, highlighted several infectious diseases as crucial targets for prevention. These infections were selected based on a thorough assessment of factors such as transmissibility, infectivity, severity, and evolu...

Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey)...

Background Although SARS-CoV-2 neutralising antibodies protect against severe COVID-19, whether circulating IgG titres reflect underlying host capacity to neutralise wild type (WT) and variants of concern (VOC) and what IgG threshold reflects sufficient neutralising capacity remains unclear. Methods In plasma from individuals in the All Ireland In...

Background The immunological memory to SARS-CoV-2 (SCV-2) vaccination has multiple components, with robust antibody (Ab) and B cell responses demonstrated post vaccination. The extent and persistence of T cell responses to vaccination remains unclear. We explored SCV-2 specific Ab, B cell and T cell responses to 3rd dose vaccine and their relations...

SARS-CoV-2 neutralising antibodies provide protection against COVID-19. Evidence from early vaccine trials suggested binding antibody thresholds could serve as surrogate markers of neutralising capacity, but whether these thresholds predict sufficient neutralising capacity against variants of concern (VOCs), and whether this is impacted by vaccine...

Obesity is a known risk factor for severe respiratory tract infections. In this prospective study, we assessed the impact of being obese or overweight on longitudinal SARS-CoV-2 humoral and cellular responses up to 18 months after infection. 274 patients provided blood samples at regular time intervals up to 18 months including obese (BMI ≥30, n=32...

Introduction Influenza vaccines play a vital role in protecting individuals from influenza virus infection and severe illness. However, current influenza vaccines have suboptimal efficacy, which is further reduced in cases where the vaccine strains do not match the circulating strains. One strategy to enhance the efficacy of influenza vaccines is b...

The endemic human coronavirus (HCoV) circulates worldwide yet remain understudied and unmitigated. The observation of elevated levels of HCoV reactive antibodies in COVID-19 patients highlights the urgent necessity of better understanding of HCoV specific immunity. Here, we characterized in-depth the de novo SARS-CoV-2 specific antibody responses a...

Influenza vaccines play a vital role in protecting individuals from influenza virus infection and severe illness. However, current influenza vaccines have suboptimal efficacy, which is further reduced in cases where the vaccine strains do not match the circulating strains. One strategy to enhance the efficacy of influenza vaccines is by extended an...

The public varied in how aware they were of the threat and the need for taking precautions in the initial phase of the COVID-19 pandemic. Some may assume that they were infected partly due to underestimating the pandemic risk. We measured perceived risk of infection, exposure to potentially infectious situations and compliance to infection control...

Background Preventing infection in healthcare workers (HCWs) is crucial for protecting healthcare systems during the COVID-19 pandemic. Here, we investigated the seroepidemiology of SARS-CoV-2 in HCWs in Norway with low-transmission settings. Methods From March 2020, we recruited HCWs at four medical centres. We determined infection by SARS-CoV-2...

Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibite...

A hallmark of patients with autoimmune polyendocrine syndrome type 1 (APS-1) is serological neutralizing autoantibodies against type 1 interferons (IFN-I). The presence of these antibodies has been associated with severe course of COVID-19. The aims of this study were to investigate SARS-CoV-2 vaccine tolerability and immune responses in a large co...

Abstract Background The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical developmen...

Background: The burden of COVID-19 in children and adolescents has increased during the delta and omicron waves, necessitating studies of long-term symptoms such as fatigue, dyspnoea and cognitive problems. Furthermore, immune responses in relation to persisting symptoms in younger people have not been well characterised. In this cohort study, we...

Introduction The haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox...

Background: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial–related educational and promotional tools for th...

Introduction External Quality Assessment (EQA) schemes are designed to provide a snapshot of laboratory proficiency, identifying issues and providing feedback to improve laboratory performance and inter-laboratory agreement in testing. Currently there are no international EQA schemes for seasonal influenza serology testing. Here we present a feasib...

Objectives Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Methods Home-dwelling old (n=100, median 86 years) and younger adults (n=449, median 38 years)...

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...

Background: Comparative data on COVID-19 among health care workers (HCWs) in different health care settings are scarce. This study investigated the rates of previous COVID-19 among HCWs in nursing homes, hospitals and a municipal emergency room (ER). Methods: We prospectively included 747 HCWs: 313 from nursing homes, 394 from hospitals and 40 from...

BACKGROUND The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial–related educational and promotional tools for the...

Despite the knowledge that cell-mediated immunity (CMI) contributes to the reduction of severe influenza infection, transmission, and disease outcome, the correlates of protection for cell-mediated immunity remain still unclear. Therefore, measuring the magnitude and quality of influenza-specific T cell responses in a harmonized way is of utmost im...

The aim of this study was to evaluate the performances of three commercially available antibody assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at different time points following SARS-CoV-2 infection. Sera from 536 cases, including 207 SARS-CoV-2 PCR positive, were tested for SARS-CoV-2 antibodies...

Influenza continues to be the most important cause of viral respiratory disease, despite the availability of vaccines. Today’s evaluation of influenza vaccines mainly focuses on the quantitative and functional analyses of antibodies to the surface proteins haemagglutinin (HA) and neuraminidase (NA). However, there is an increasing interest in measu...

The high genetic and antigenic variability of influenza virus and the repeated exposures of individuals to the virus over time account for the human immune responses toward this pathogen to continuously evolve during the lifespan of an individual. Influenza-specific immune memory to past strains has been shown to affect the immune responses to subs...

To map the public information about COVID-19 vaccines and vaccine trials in Europe, we have compiled an inventory of online communication materials from official sources (e.g., governments, public agencies, and NGOs) via directed online research. While information for the general public was abundant across Europe, we found a large variation in numb...

Background: The burden and duration of persistent symptoms after non-severe COVID-19 remains uncertain. This study aimed to assess post-infection symptom trajectories in home-isolated COVID-19 cases compared to age- and time-period matched seronegative controls, and investigate immunological correlates of long COVID. Methods: A prospective case-co...

Current vaccination strategies against influenza focus on generating an antibody response against the viral haemagglutination surface protein, however there is increasing interest in neuraminidase (NA) as a target for vaccine development. A critical tool for development of vaccines that target NA or include an NA component is available validated se...

Introduction The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study...

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 ye...

Coronavirus disease 2019 (COVID-19) pandemic has demonstrated how vaccines play a key role in the fight against infectious diseases. However, identifying suitable study subjects can be challenging in clinical trials. Therefore, within the VACCELERATE Consortium, a volunteer registry for vaccine trial participation has been established. VACCELERATE’...

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, micro...

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...

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...

The ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the initiation of unprecedented research efforts to understand the pathogenesis mediated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). More knowledge is needed regarding the cell type-specific cytopathology and its impact on cellular tropism. Furthermore, the imp...

Background Neutralizing antibodies are important for protection against the pandemic SARS-CoV-2 virus, and long-term memory responses determine the risk of re-infection or boosting after vaccination. T-cellular responses are considered important for partial protection against novel variants of concern. Methods A prospective cohort of hospitalized...

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CA...

The number of people who have survived COVID-19 is overwhelming – official figures approach half a billion (https://covid19.who.int). Thus, any long-term consequences in COVID-19 survivors could have a huge impact on public health and on healthcare services in the coming months and years, with potentially 100 million individuals affected.

Background In 2009, a novel influenza A/H1N1pdm09 emerged and caused a pandemic. This strain continued to circulate and was therefore included in the seasonal vaccines up to the 2016/2017-season. This provided a unique opportunity to study the long-term antibody responses to H1N1pdm09 in healthcare workers (HCW) with a different vaccination history...

The International Society for Influenza and other Respiratory Virus Diseases (isirv) and the WHO held a joint virtual conference from 19th-21st October 2021. While there was a major focus on the global response to the SARS-CoV-2 pandemic, including antivirals, vaccines and surveillance strategies, papers were also presented on treatment and prevent...

The highly pathogenic avian influenza H5N1 viruses constantly evolve and give rise to novel variants that have caused widespread zoonotic outbreaks and sporadic human infections. Therefore, vaccines capable of eliciting broadly protective antibody responses are desired and under development. We here investigated the magnitude, kinetics and protecti...

The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF ® 09b contains t...

Antibodies to influenza surface protein neuraminidase (NA) have been found to reduce disease severity and may be an independent correlate of protection. Despite this, current influenza vaccines have no regulatory requirements for the quality or quantity of the NA antigen and are not optimized for induction of NA-specific antibodies. Here we investi...

Annual influenza vaccination is often recommended for pregnant women and young children to reduce the risk of severe influenza. However, most studies investigating the safety, immunogenicity, and efficacy or effectiveness of influenza vaccines are conducted in healthy adults. In this evidence-based clinical review, we provide an update on the safet...

Background COVID-19 patients are extensively treated with antibiotics despite few bacterial complications. We aimed to study antibiotic use in hospitalized COVID-19 patients compared to influenza patients in two consecutive years. Furthermore, we investigated changes in antibiotic use from the first to second pandemic wave. Methods This prospectiv...

Evaluation of susceptibility to emerging SARS-CoV-2 variants of concern (VOC) requires rapid screening tests for neutralising antibodies which provide protection. We developed a receptor-binding domain specific hemagglutination test (HAT) which correlated with neutralising antibodies (R=0.74-0.82) in two independent cohorts from 798 convalescents....

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 fir...

Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza...

The hemagglutination inhibition (HAI) assay is the most commonly used serology assay to detect antibodies from influenza vaccination or influenza virus infection. This assay has been used for decades but requires improved standardization of procedures to provide meaningful data.

The effects of the COVID-19 pandemic are amplified among socially vulnerable groups, including international migrants, in terms of both disease transmission and outcomes and the consequences of mitigation measures. Migrants are overrepresented in COVID-19 laboratory-confirmed cases, hospital admissions, intensive care treatment and death statistics...

There is limited knowledge of influenza-specific immune responses and their kinetics in critically ill patients. We investigated humoral and cellular immune responses after critical influenza A/H1N1 infection and hypothesized that dysfunctionality or absence of immune responses could contribute to more severe illness. We followed 12 patients hospit...

Current influenza vaccines have a suboptimal effectiveness. The introduction of a novel A/H1N1 influenza virus in 2009 (H1N1pdm09) provided a unique opportunity to study the humoral response to the AS03-adjuvanted H1N1pdm09 vaccine and repeated annual vaccination with the homologous virus in subsequent influenza seasons. Thirty-two HCWs immunized w...

Background Households studies reflect the natural spread of SARS-CoV-2 in immunologically naive populations with limited preventive measures to control transmission. We hypothesise that seropositivity provides more accurate household attack rates than RT-PCR. Here, we investigated the importance of age in household transmission dynamics. Methods W...

Long-term complications following COVID-19 are common in hospitalised patients, but the spectrum of symptoms in milder cases remains unclear. In a Norwegian prospective cohort study of 312 patients, 61% of COVID-19 patients (247 home-isolated and 65 hospitalised) had persistent symptoms at six months, most commonly fatigue (37%), impaired concentra...

Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in healthcare workers (HCW) due to overburdened healthcare systems. However, whether infected HCW acquire protective immunity against SARS-CoV-2 is unclear. Here, we characterized SARS-CoV-2-specific antibody responses in Norwegian HCW in a pros...

Background Influenza is difficult to distinguish clinically from other acute respiratory infections. Rapid laboratory diagnosis can help initiate early effective antiviral treatment and isolation. Aim Implementing a novel point-of-care test (POCT) for influenza in the emergency department (ED) could improve treatment and isolation strategies and r...

Background Household attack rates of SARS-CoV-2 ranging from 7% to 38% have been reported, using reverse transcription polymerase chain reaction (RT-PCR) of respiratory samples. Lower attack rates were described in children, but the importance of age in household transmission dynamics remains to be clarified. Methods During the first month of the...