COVID-19

ICNARC played a major role in responding to the COVID-19 pandemic through our clinical audit, research and data services activities.

Clinical audit 

Prior to the first confirmed case of COVID-19 in the UK, ICNARC was approached by NHS England to provide analyses on the characteristics and outcomes of patients admitted to critical care with pneumonia and the numbers of available critical care beds.

On 4 March 2020, we contacted all critical care units participating in the Case Mix Programme to request that they notify ICNARC immediately of any patient with confirmed or clinically suspected COVID-19 admitted to their unit and to submit data for these patients as soon as possible. Notifications began to arrive the same day. 

On 10 March 2020, the day before the World Health Organization declared the COVID-19 outbreak to be a pandemic, we produced our first report on patients critically ill with COVID-19. This report was based on data for 13 patients. Due to the small number of patients, we shared this report with NHS England but did not circulate it more widely. 

The numbers of patients admitted to critical care with COVID-19 escalated rapidly, and on 20 March 2020 our updated report included data on 196 patients. We circulated this report to all critical care units participating in the Case Mix Programme, as well as NHS England and professional organisations, and subsequently made the report publicly available on our website. 

We continued to produce public reports weekly throughout the peaks of the pandemic, reducing to monthly when critical care admissions were lower, and subsequently to quarterly in 2022. Reports from key timepoints during the pandemic are available in the Reports section of the website. Media analytics provided by Meltwater showed that at the peak of the first wave in April 2020, news articles referencing ICNARC had a potential global reach of 4.6 billion people. 

ICNARC’s reports were one of the first sources to draw attention to the greater impact of COVID-19 on people from Black and minority ethnic groups. Analyses of Case Mix Programme data also informed decision-making by the Joint Committee on Vaccination and Immunisation (JCVI) on which groups to prioritise for vaccination. 

Research 

ICNARC, in partnership with Imperial College London, is the UK coordinating centre for the global REMAP-CAP platform trial. REMAP-CAP was funded as part of a European consortium for pandemic preparedness, designed to evaluate interventions for community-acquired pneumonia when there was no pandemic, but to be ready to adapt quickly in the event of a pandemic. As the emerging threat of COVID-19 was recognised, this plan was put into action with the changes approved on 31 January 2020 and the first patient with COVID-19 recruited on 10 March 2020. 

On 1 April 2020, the UK Chief Medical Officers identified REMAP-CAP as national priority clinical trial, encouraging all NHS organisations to make every effort to enrol patients. With additional funding from the National Institute for Health and Care Research, and with ICNARC research staff redirected from other studies, the number of UK sites participating in REMAP-CAP increased from 10 prior to the pandemic to 148 – almost half of the global total sites in the trial.

The rapid escalation of the trial allowed REMAP-CAP to identify effective treatments (for example, steroids and interleukin-6 receptor antagonists) quickly enough for thousands of future patients to benefit from these treatments during the pandemic. It also helped to identify treatments that were ineffective (for example, convalescent plasma) or even harmful (for example, lopinavir-ritonavir and hydroxychloroquine) preventing further harm from being done by off-label use of these potential treatments. 

Data services 

In addition to our own reporting, ICNARC aimed to make Case Mix Programme data as widely available as possible (subject to appropriate information governance) to inform the pandemic response. 

Regular daily data flows into the NHS England data lake commenced on 25 March 2020 and continued throughout the pandemic. Regular data flows were also established to the NHS Digital Trusted Research Environment and the SAIL Databank in Wales. Case Mix Programme data were linked with primary care data in the OpenSAFELY platform, QResearch and the Clinical Practice Research Datalink (CPRD). 

We also provided linked data from the Case Mix Programme to clinical trials including RECOVERY, RECOVERY-RS and REALIST. 

Publications

Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, Hunt D, Mei XW, Dixon S, Zaccardi F, Khunti K, Watkinson P, Coupland CAC, Doidge J, Harrison DA, Ravanan R, Sheikh A, Robertson C, Hippisley-Cox J. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med 2021; 27(12):2144-53. http://dx.doi.org/10.1038/s41591-021-01556-7

Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD, 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 DJ, Hayward C, Yang J, Knight J, Summers C, Shankar-Hari M, Klenerman P, Turtle L, Ho A, Moore SC, Hinds C, Horby P, Nichol A, Maslove D, Ling L, McAuley D, Montgomery H, Walsh T, Pereira AC, Renieri A, Shen X, Ponting CP, Fawkes A, Tenesa A, Caulfield M, Scott R, Rowan K, Murphy L, Openshaw PJM, Semple MG, Law A, Vitart V, Wilson JF, Baillie JK. Genetic mechanisms of critical illness in COVID-19. Nature 2021; 591(7848):92-8. http://dx.doi.org/10.1038/s41586-020-03065-y

Patone M, Thomas K, Hatch R, Tan PS, Coupland C, Liao W, Mouncey P, Harrison D, Rowan K, Horby P, Watkinson P, Hippisley-Cox J. Mortality and critical care unit admission associated with the SARS-CoV-2 lineage B.1.1.7 in England: an observational cohort study. Lancet Infect Dis 2021; 21(11):1518-28. http://dx.doi.org/10.1016/s1473-3099(21)00318-2

Richards-Belle A, Orzechowska I, Doidge J, Thomas K, Harrison DA, Koelewyn A, Christian MD, Shankar-Hari M, Rowan KM, Gould DW. Critical care outcomes, for the first 200 patients with confirmed COVID-19, in England, Wales and Northern Ireland: A report from the ICNARC Case Mix Programme. J Intensive Care Soc 2021; 22(4):270-9. http://dx.doi.org/10.1177/1751143720961672

Ratcliff J, Nguyen D, Fish M, Rynne J, Jennings A, Williams S, Al-Beidh F, Bonsall D, Evans A, Golubchik T, Gordon AC, Lamikanra A, Tsang P, Ciccone NA, Leuscher U, Slack W, Laing E, Mouncey PR, Ziyenge S, Oliveira M, Ploeg R, Rowan KM, Shankar-Hari M, Roberts DJ, Menon DK, Estcourt L, Simmonds P, Harvala H. Virological Characterization of Critically Ill Patients With COVID-19 in the United Kingdom: Interactions of Viral Load, Antibody Status, and B.1.1.7 Infection. J Infect Dis 2021; 224(4):595-605. http://dx.doi.org/10.1093/infdis/jiab283

Proudfoot AG, O'Brien B, Schilling R, Gould DW, McGlennan A. Rapid establishment of a COVID-19 critical care unit in a convention centre: the Nightingale Hospital London experience. Intensive Care Med 2021; 47(3):349-51. http://dx.doi.org/10.1007/s00134-020-06334-6

Dongelmans DA, Quintairos A, Buanes EA, Aryal D, Bagshaw S, Bendel S, Bonney J, Burghi G, Fan E, Guidet B, Haniffa R, Hashimi M, Hashimoto S, Ichihara N, Vijayaraghavan BKT, Lone N, Del Pilar Arias Lopez M, Mazlam MZ, Okamoto H, Perren A, Rowan K, Sigurdsson M, Silka W, Soares M, Viana G, Pilcher D, Beane A, Salluh JIF. Worldwide clinical intensive care registries response to the pandemic: An international survey. J Crit Care 2022; 71:154111. http://dx.doi.org/10.1016/j.jcrc.2022.154111

Edwards JM, Nolan JP, Soar J, Smith GB, Reynolds E, Carnall J, Rowan KM, Harrison DA, Doidge JC. Impact of the COVID-19 pandemic on in-hospital cardiac arrests in the UK. Resuscitation 2022; 173:4-11. http://dx.doi.org/10.1016/j.resuscitation.2022.02.007

Tran A, Fernando SM, Rochwerg B, Barbaro RP, Hodgson CL, Munshi L, MacLaren G, Ramanathan K, Hough CL, Brochard LJ, Rowan KM, Ferguson ND, Combes A, Slutsky AS, Fan E, Brodie D. Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Lancet Respir Med 2023; 11(3):235-44. http://dx.doi.org/10.1016/s2213-2600(22)00296-x

Swets MC, Kerr S, Scott-Brown J, Brown AB, Gupta R, Millar JE, Spata E, McCurrach F, Bretherick AD, Docherty A, Harrison D, Rowan K, Young N, Groeneveld GH, Dunning J, Nguyen-Van-Tam JS, Openshaw P, Horby PW, Harrison E, Staplin N, Semple MG, Lone N, Baillie JK. Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity. Nat Commun 2023; 14(1):7374. http://dx.doi.org/10.1038/s41467-023-42205-6

Gao M, Aveyard P, Lindson N, Hartmann-Boyce J, Watkinson P, Young D, Coupland C, Clift AK, Harrison D, Gould D, Pavord ID, Smith M, Hippisley-Cox J. Association between smoking, e-cigarette use and severe COVID-19: a cohort study. Int J Epidemiol 2022; 51(4):1062-72. http://dx.doi.org/10.1093/ije/dyac028

Fish M, Rynne J, Jennings A, Lam C, Lamikanra AA, Ratcliff J, Cellone-Trevelin S, Timms E, Jiriha J, Tosi I, Pramanik R, Simmonds P, Seth S, Williams J, Gordon AC, Knight J, Smith DJ, Whalley J, Harrison D, Rowan K, Harvala H, Klenerman P, Estcourt L, Menon DK, Roberts D, Shankar-Hari M. Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial. Intensive Care Med 2022; 48(11):1525-38. http://dx.doi.org/10.1007/s00134-022-06869-w

Pairo-Castineira E, Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, Oosthuyzen W, Kousathanas A, Richmond A, Millar J, Russell CD, Malinauskas T, Thwaites R, Morrice K, Keating S, Maslove D, Nichol A, Semple MG, Knight J, Shankar-Hari M, Summers C, Hinds C, Horby P, Ling L, McAuley D, Montgomery H, Openshaw PJM, Begg C, Walsh T, Tenesa A, Flores C, Riancho JA, Rojas-Martinez A, Lapunzina P, Yang J, Ponting CP, Wilson JF, Vitart V, Abedalthagafi M, Luchessi AD, Parra EJ, Cruz R, Carracedo A, Fawkes A, Murphy L, Rowan K, Pereira AC, Law A, Fairfax B, Hendry SC, Baillie JK. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19. Nature 2023; 617(7962):764-8. http://dx.doi.org/10.1038/s41586-023-06034-3