Periodic Reporting for period 1 - POINT (Preventing non-communicable diseases caused by the post-acute phase of cOvid-19 INfecTion)
Okres sprawozdawczy: 2024-01-01 do 2025-06-30
COVID-19 does not always end with a negative test. Many people face an increased risk of heart, lung and kidney problems months or years after the initial illness, the post-acute phase (PAP) of COVID-19. POINT brings together population data, blood-based measurements and advanced laboratory and computational models to understand why this happens and who is at greatest risk, and to turn that knowledge into practical guidance for clinicians.
The project links two large European registry cohorts (pre-pandemic and during-pandemic) with rich health, prescription and socio-demographic data to map the longer-term burden of non-communicable diseases (NCDs) after COVID-19. In parallel, clinical cohorts in Greece and Denmark provide longitudinal plasma and serum samples, paired between acute illness and follow-up, that are analysed with deep proteomic methods to reveal circulating factors associated with organ injury, cardiovascular fitness and inflammation.
Laboratory teams use standardised human 2D cell cultures and 3D organoids of lung, kidney and vascular tissues to test how patient plasma and selected protein mixtures affect cell stress, energy production, fibrosis and senescence. These readouts, together with registry and proteomics data, are integrated into “virtual twin” models that simulate disease mechanisms and forecast individual risk.
Social sciences play a central role: POINT works with general practitioners (GPs) to understand guideline use and barriers to uptake, studies how belief systems shape adoption, and liaises with standards bodies to ensure that emerging tools are usable, explainable and interoperable in everyday care.
Expected impact includes earlier identification and follow-up of people at risk of PAP-related NCDs, better targeted monitoring panels for heart, lung and kidney health, and decision support that helps clinicians act on risk in a consistent and transparent way across Europe. At population scale, registry analyses provide evidence to plan services and reduce long-term health and economic burdens.
The project links two large European registry cohorts (pre-pandemic and during-pandemic) with rich health, prescription and socio-demographic data to map the longer-term burden of non-communicable diseases (NCDs) after COVID-19. In parallel, clinical cohorts in Greece and Denmark provide longitudinal plasma and serum samples, paired between acute illness and follow-up, that are analysed with deep proteomic methods to reveal circulating factors associated with organ injury, cardiovascular fitness and inflammation.
Laboratory teams use standardised human 2D cell cultures and 3D organoids of lung, kidney and vascular tissues to test how patient plasma and selected protein mixtures affect cell stress, energy production, fibrosis and senescence. These readouts, together with registry and proteomics data, are integrated into “virtual twin” models that simulate disease mechanisms and forecast individual risk.
Social sciences play a central role: POINT works with general practitioners (GPs) to understand guideline use and barriers to uptake, studies how belief systems shape adoption, and liaises with standards bodies to ensure that emerging tools are usable, explainable and interoperable in everyday care.
Expected impact includes earlier identification and follow-up of people at risk of PAP-related NCDs, better targeted monitoring panels for heart, lung and kidney health, and decision support that helps clinicians act on risk in a consistent and transparent way across Europe. At population scale, registry analyses provide evidence to plan services and reduce long-term health and economic burdens.
In the first 18 months, POINT established the linked registry cohorts and data pipelines, enabling time-to-event and multi-state analyses of NCD incidence and severity by age, sex, education and migration, with vaccination and reinfections captured as time-varying exposures. The Greek cohort recruited participants across three groups (healthy comparators; COVID-19 survivors with and without acute organ dysfunction) and began 48-month follow-up with harmonised tests and biosampling; 100 Greek samples (80 patients, 20 controls) have already been shipped for discovery proteomics, with paired acute and one-year samples enabling longitudinal comparison. The Danish cohort enrolled 222 participants, with 152 EDTA-plasma sets shipped to UCPH; samples are blinded to the analysis team.
To maximise discovery, the consortium used Olink Explore HT (~5,400 proteins), which subsumes the originally planned focused panels and provides a richer basis for down-selection into scalable marker sets. Bioinformatic processing of the first 100 samples is underway.
On the experimental side, a validated panel of 2D/3D human models (lung, kidney, vascular endothelium) and screening SOPs was delivered, covering transcript/protein stress markers, confocal and flow-based phenotyping, senescence, bioenergetics (Seahorse XF) and RNA-seq. Stress-inducing candidate factors are being prioritised by integrating proteomic fold-changes with in-vitro response magnitudes and literature evidence; these are tested as individual proteins and in “synthetic plasma” mixes to assess dose–response and synergy.
Computationally, a baseline virtual-twin stack (Endogenics™/EndoPathways) was stood up with model import (SBML), plausibility checks and time-resolved simulation, ready to ingest features from WP1–WP3 and support “what-if” analyses. GP-facing requirements for a clinician decision-support prototype were collected to ensure the modelling outputs meet frontline needs.
To maximise discovery, the consortium used Olink Explore HT (~5,400 proteins), which subsumes the originally planned focused panels and provides a richer basis for down-selection into scalable marker sets. Bioinformatic processing of the first 100 samples is underway.
On the experimental side, a validated panel of 2D/3D human models (lung, kidney, vascular endothelium) and screening SOPs was delivered, covering transcript/protein stress markers, confocal and flow-based phenotyping, senescence, bioenergetics (Seahorse XF) and RNA-seq. Stress-inducing candidate factors are being prioritised by integrating proteomic fold-changes with in-vitro response magnitudes and literature evidence; these are tested as individual proteins and in “synthetic plasma” mixes to assess dose–response and synergy.
Computationally, a baseline virtual-twin stack (Endogenics™/EndoPathways) was stood up with model import (SBML), plausibility checks and time-resolved simulation, ready to ingest features from WP1–WP3 and support “what-if” analyses. GP-facing requirements for a clinician decision-support prototype were collected to ensure the modelling outputs meet frontline needs.
POINT’s novelty is the end-to-end integration: (i) population-scale registry cohorts that quantify PAP-related NCD risk; (ii) deep proteomic profiles that move beyond short marker lists; (iii) human organoid/cell models that mechanistically test real patient plasma and defined factor mixes; and (iv) virtual twins that connect pathway dynamics to clinical trajectories. This enables hypothesis testing across scales, cell to system to population, something single-domain studies cannot do.
Early insights include differential declines in inflammatory markers over time and patterns consistent with immune suppression in some Long-COVID trajectories, strengthening the case for targeted, time-aware monitoring rather than one-off tests. The “synthetic plasma” strategy goes beyond correlative omics by recreating patient-like milieus in vitro to test causality and synergy, supporting more rational selection of protective drug mechanisms to take forward.
For wider uptake, key needs are: external validation of registry-based risk models; down-selection from discovery proteomics to cost-effective panels; continued standardisation of organoid assay readouts; and user-centered design of a transparent, auditable CDSS integrated with clinical workflows. POINT has initiated all four.
Early insights include differential declines in inflammatory markers over time and patterns consistent with immune suppression in some Long-COVID trajectories, strengthening the case for targeted, time-aware monitoring rather than one-off tests. The “synthetic plasma” strategy goes beyond correlative omics by recreating patient-like milieus in vitro to test causality and synergy, supporting more rational selection of protective drug mechanisms to take forward.
For wider uptake, key needs are: external validation of registry-based risk models; down-selection from discovery proteomics to cost-effective panels; continued standardisation of organoid assay readouts; and user-centered design of a transparent, auditable CDSS integrated with clinical workflows. POINT has initiated all four.