Periodic Reporting for period 2 - REACT (Respiratory Host-Pathogen Interaction)
Berichtszeitraum: 2024-02-01 bis 2025-07-31
Respiratory infections such as influenza, RSV, and COVID-19 remain leading global health threats, causing high morbidity, mortality, and economic disruption. The COVID-19 pandemic highlighted major gaps in preparedness, including limited understanding of why individuals respond so differently to infection and recovery, and how social and demographic factors shape outcomes.
REACT addresses these challenges by investigating the host–pathogen interface across the three viruses. Its objectives are to build diverse retrospective and prospective cohorts, generate comprehensive viral and host datasets, and use advanced models such as organoids and lung-on-chip systems to validate findings. Integrating genomics, immunology, and clinical data with bioinformatics and machine learning enables the development of predictive models for patient outcomes and clinical trial readiness.
The project’s pathway to impact combines scientific excellence, societal relevance, and strategic alignment. Scientifically, REACT advances knowledge of immune and genetic determinants of infection. Societally, it prioritises vulnerable groups, such as the elderly and people living with HIV, and integrates social sciences and humanities by analysing demographic and socio-economic influences on disease and by engaging patients and health authorities. Strategically, REACT contributes interoperable datasets and tools to European infrastructures, directly supporting pandemic preparedness and public health resilience.
By creating knowledge, resources, and platforms that are FAIR, open, and reusable, REACT strengthens Europe’s capacity to respond to respiratory epidemics and pandemics. The project’s results are expected to have wide impact, from guiding clinical management to informing public health strategies and supporting innovation in diagnostics, vaccines, and therapies.
REACT addresses these challenges by investigating the host–pathogen interface across the three viruses. Its objectives are to build diverse retrospective and prospective cohorts, generate comprehensive viral and host datasets, and use advanced models such as organoids and lung-on-chip systems to validate findings. Integrating genomics, immunology, and clinical data with bioinformatics and machine learning enables the development of predictive models for patient outcomes and clinical trial readiness.
The project’s pathway to impact combines scientific excellence, societal relevance, and strategic alignment. Scientifically, REACT advances knowledge of immune and genetic determinants of infection. Societally, it prioritises vulnerable groups, such as the elderly and people living with HIV, and integrates social sciences and humanities by analysing demographic and socio-economic influences on disease and by engaging patients and health authorities. Strategically, REACT contributes interoperable datasets and tools to European infrastructures, directly supporting pandemic preparedness and public health resilience.
By creating knowledge, resources, and platforms that are FAIR, open, and reusable, REACT strengthens Europe’s capacity to respond to respiratory epidemics and pandemics. The project’s results are expected to have wide impact, from guiding clinical management to informing public health strategies and supporting innovation in diagnostics, vaccines, and therapies.
During the second reporting period, REACT has made substantial technical and scientific progress across its core objectives. Cohort development and biobanking advanced significantly, with expansion of both retrospective and prospective collections in Denmark and Spain. By the end of the period, more than 4,400 samples had been collected or gained, including blood, swabs, PBMCs, and lung tissue. These resources provide the backbone for ongoing genetic, immunological, and virological analyses.
On the virological side, the consortium carried out large-scale sequencing of circulating SARS-CoV-2, influenza, and RSV strains, generating datasets of high relevance to ongoing public health surveillance. A new RSV sequencing protocol was successfully developed, and viral isolates were expanded in BSL-3 facilities, resulting in a virus library that includes recent SARS-CoV-2 subvariants (BA.2.86 JN.1) influenza A and B strains, and RSV A and B. These isolates were distributed across the consortium for downstream immunological and modelling studies.
Progress was also marked in host genetics and immunology. Analyses in WP4 demonstrated that skewed X-inactivation patterns may influence COVID-19 severity in women, highlighting the value of integrating sex-specific analyses. Genome-wide association studies, HLA analyses, and polygenic risk scores were performed across multiple cohorts, providing insight into genetic susceptibility to respiratory infections. Parallel work in WP5 and WP6 advanced the mapping of T and B cell responses.
On the virological side, the consortium carried out large-scale sequencing of circulating SARS-CoV-2, influenza, and RSV strains, generating datasets of high relevance to ongoing public health surveillance. A new RSV sequencing protocol was successfully developed, and viral isolates were expanded in BSL-3 facilities, resulting in a virus library that includes recent SARS-CoV-2 subvariants (BA.2.86 JN.1) influenza A and B strains, and RSV A and B. These isolates were distributed across the consortium for downstream immunological and modelling studies.
Progress was also marked in host genetics and immunology. Analyses in WP4 demonstrated that skewed X-inactivation patterns may influence COVID-19 severity in women, highlighting the value of integrating sex-specific analyses. Genome-wide association studies, HLA analyses, and polygenic risk scores were performed across multiple cohorts, providing insight into genetic susceptibility to respiratory infections. Parallel work in WP5 and WP6 advanced the mapping of T and B cell responses.
REACT has generated important scientific results during the second reporting period that advance understanding of respiratory infections and support Europe’s preparedness for future epidemics. Large-scale cohorts and biobanks have been successfully established in Denmark, Spain, and South Africa, providing well-characterised clinical and demographic data together with thousands of biological samples. These collections now serve as a major resource for genetic, immunological, and virological analyses.
On the virology side, sequencing of circulating SARS-CoV-2, influenza, and RSV strains has produced comprehensive datasets, and a dedicated RSV sequencing protocol has been validated. A growing library of viral isolates, including recent SARS-CoV-2 subvariants, influenza A and B, and RSV A and B, is now available for consortium-wide use. These resources are already being used to infect organoid and lung-chip models, enabling translational studies.
Results in host genetics and immunity include identification of sex-specific genetic factors influencing COVID-19 outcomes, novel T cell epitopes for influenza and RSV, and a previously undescribed subset of memory B cells associated with infection outcomes. Data from the South African cohort revealed immune signatures and genetic variation that shape disease severity independently of HIV-1 status. Together, these results are uncovering key determinants of individual variation in disease trajectories.
The project’s advanced organoid and lung-chip models are now functional platforms, capable of modelling infection and immune responses in patient-derived tissues.
On the virology side, sequencing of circulating SARS-CoV-2, influenza, and RSV strains has produced comprehensive datasets, and a dedicated RSV sequencing protocol has been validated. A growing library of viral isolates, including recent SARS-CoV-2 subvariants, influenza A and B, and RSV A and B, is now available for consortium-wide use. These resources are already being used to infect organoid and lung-chip models, enabling translational studies.
Results in host genetics and immunity include identification of sex-specific genetic factors influencing COVID-19 outcomes, novel T cell epitopes for influenza and RSV, and a previously undescribed subset of memory B cells associated with infection outcomes. Data from the South African cohort revealed immune signatures and genetic variation that shape disease severity independently of HIV-1 status. Together, these results are uncovering key determinants of individual variation in disease trajectories.
The project’s advanced organoid and lung-chip models are now functional platforms, capable of modelling infection and immune responses in patient-derived tissues.