Outbreak analysis platform

Outbreak data analysis platform

The data analysis platform provides a unique combination of linked, curated data from UK sovereign data assets, together with a flexible high performance compute space. Created for Covid-19 research, the ISARIC4C data analysis platform combines the data safeguards of an NHS trusted research environment, with >£100M of exabyte-scale computational capacity on the UK national supercomputer. This creates a unique opportunity to combine clinical, biological, genomics and virology research in as secure, openly-accessible framework.

Data held

The outbreak analysis platform was developed by ISARIC4C to encourgage and facilitate research by collating, linking and curating clinical and research data, enabling deep integrative analyses of multi-omic disease profiling, stratified by viral variant, clinical phenotype and outcome.

Figure 1: Structure of the ISARIC4C Analysis Platform

This platform now serves as a hub for a coordinated UK national research response to COVID-19. Data are included from:

  • ISARIC4C tier 0: (unconsented) prospective clinical data from 210,963 cases
  • ISARIC4C tiers 1 and 2: serial multiomic assays from research samples of blood, respiratory secretions, urine, and stool from 2,358 cases
  • COG-UK: (unconsented) summary variant data from COG-UK viral sequencing study is already included for matched patients
  • GenOMICC study complete data: microarray and whole genome sequence data from 13,239 cases
  • PHOSP complete data: follow-up clinical and biological data generated by the Post-Hospitalisation for COVID-19 follow-up study (1,075 cases)
  • UK-CIC: deep immunological phenotyping data from across the UK Coronavirus Immunology Consortium, using ISARIC4C samples and local collections.

Research data within the analysis platform is already linked to:

  • NHS Scotland primary, secondary care and death records
  • NHS Digital health records data

In future, plans are in place to transfer data to link with:

  • ICNARC and SICSAG critical care audit databases
  • NIMS National Immunisation Dataset
  • Pillar 1 testing
  • Pillar 2 testing
  • ONS

Research outputs

The ISARIC Coronavirus Clinical Characterisation Consortium (4C) is the largest observational study of hospitalised patients with COVID-19 anyhwere in the world. By generating, integrating and analysing clinical, biological, genetic and virological data on patients with Covid-19 in UK hospitals, ISARIC4C has:

  • provided essential weekly updates to SAGE that guide the public health response isaric4c.net/reports/,
  • quantified the role of age, comorbid illness and obesity in disease severity,1
  • identified the substantial effect of nosocomial transmission of Covid-19 within hospitals SPI-M/SAGE report,
  • created the global standard ISARIC4C score for prognostication isaric4c.net/risk,2
  • elucidated cytokine patterns underlying disease mechanisms,3
  • identified host genetic mechanisms of disease,4
  • provided key evidence underlying the choice of therapeutic agents for clinical trials3,4
  • provided data supporting identification of high risk groups for vaccination (highlighted in No10 briefing)
  • provided real world data on vaccine effectiveness and failure (SAGE 87 Egan et al, Egan et al.)

Because of these and other achievements (see isaric4c.net/outputs), ISARIC4C was used as exemplar by the National Institte of Healthcare Research for pandemic preparedness research resulting in real patient benefit.

Analysis platform structure

There are two routes of access to the analysis platform (Figure 1): 1. NHS Trusted Research Environment (Safe Haven) for access to personal clinical data and data collected without explicit consent. 2. Rapid-access flexible compute for access to non-disclosive research data collected with explicit consent.

Within both of these environments there is an additional division in the data: 1. Publishable “open access” data which any user can use and report as they wish, according to data protection and privacy rules; 2. Embargoed active research data, shared by academic investigators and available for linked analysis but not for publication without agreement from all contributors.

This design is intended to build trust in order to encourage immediate contributions of research data from academic collaborators.

Figure 2: ISARIC4C study and data analysis platform

Future plans

Rapid addition of viral sequence data from the COG-UK platform will enable real-time detection of the clinical impact of new viral strains, in-depth biological study of reinfection, and host:pathogen interactions at a genetic and mechanistic level.

References

1. Docherty, A.B., Harrison, E.M., Green, C.A., Hardwick, H.E., Pius, R., Norman, L., Holden, K.A., Read, J.M., Dondelinger, F., Carson, G., Merson, L., Lee, J., Plotkin, D., Sigfrid, L., Halpin, S., Jackson, C., Gamble, C., Horby, P.W., Nguyen-Van-Tam, J.S., Ho, A., Russell, C.D., Dunning, J., Openshaw, P.J., Baillie, J.K. & Semple, M.G. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: Prospective observational cohort study. BMJ 369, (2020).
2. Knight, S.R., Ho, A., Pius, R., Buchan, I., Carson, G., Drake, T.M., Dunning, J., Fairfield, C.J., Gamble, C., Green, C.A., Gupta, R., Halpin, S., Hardwick, H.E., Holden, K.A., Horby, P.W., Jackson, C., Mclean, K.A., Merson, L., Nguyen-Van-Tam, J.S., Norman, L., Noursadeghi, M., Olliaro, P.L., Pritchard, M.G., Russell, C.D., Shaw, C.A., Sheikh, A., Solomon, T., Sudlow, C., Swann, O.V., Turtle, L.C., Openshaw, P.J., Baillie, J.K., Semple, M.G., Docherty, A.B. & Harrison, E.M. Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: Development and validation of the 4C mortality score. BMJ (Clinical research ed.) 370, m3339(2020).
3. Thwaites, R.S., Uruchurtu, A.S.S., Siggins, M.K., Liew, F., Russell, C.D., Moore, S.C., Fairfield, C., Carter, E., Abrams, S., Short, C.-E., Thaventhiran, T., Bergstrom, E., Gardener, Z., Ascough, S., Chiu, C., Docherty, A.B., Hunt, D., Crow, Y.J., Solomon, T., Taylor, G.P., Turtle, L., Harrison, E.M., Dunning, J., Semple, M.G., Baillie, J.K., Openshaw, P.J. & Investigators**, on behalf of the I. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Science Immunology 6, (2021).
4. Pairo-Castineira, E., Clohisey, S., Klaric, L., Bretherick, A.D., Rawlik, K., Pasko, D., Walker, S., Parkinson, N., Fourman, M.H., Russell, C.D., Furniss, J., Richmond, A., Gountouna, E., Wrobel, N., Harrison, D., Wang, B., Wu, Y., Meynert, A., Griffiths, F., Oosthuyzen, W., Kousathanas, A., Moutsianas, L., Yang, Z., Zhai, R., Zheng, C., Grimes, G., Beale, R., Millar, J., Shih, B., Keating, S., Zechner, M., Haley, C., Porteous, D.J., Hayward, C., Yang, J., Knight, J., Summers, C., Shankar-Hari, M., Klenerman, P., Turtle, L., Ho, A., Moore, S.C., Hinds, C., Horby, P., Nichol, A., Maslove, D., Ling, L., McAuley, D., Montgomery, H., Walsh, T., Pereira, A.C., Renieri, A., Shen, X., Ponting, C.P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P.J.M., Semple, M.G., Law, A., Vitart, V., Wilson, J.F. & Baillie, J.K. Genetic mechanisms of critical illness in COVID-19. Nature 591, 92–98(2021).