Imperial College London
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Professor Anthony Gordon

Faculty of Medicine, Department of Surgery & Cancer

Chair in Anaesthesia and Critical Care
 
 
 
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Contact

 

anthony.gordon

 
 
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Location

 

ICUQueen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Fish:2022:10.1007/s00134-022-06869-w,
author = {Fish, M and Rynne, J and Jennings, A and Lam, C and Lamikanra, AA and Ratcliff, J and Cellone-Trevelin, S and Timms, E and Jiriha, J and Tosi, I and Pramanik, R and Simmonds, P and Seth, S and Williams, J and Gordon, AC and Knight, J and Smith, DJ and Whalley, J and Harrison, D and Rowan, K and Harvala, H and Klenerman, P and Estcourt, L and Menon, DK and Roberts, D and Shankar-Hari, M},
doi = {10.1007/s00134-022-06869-w},
journal = {Intensive Care Medicine},
pages = {1525--1538},
title = {Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial},
url = {http://dx.doi.org/10.1007/s00134-022-06869-w},
volume = {48},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - PurposeBenefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs .MethodsWe tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) .ResultsUnsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (− 1, 21) vs 10 (− 1, to 21) in subphenotype-2; 1.5 (− 1, 21) vs 12 (− 1, to 21) in suphenotype-3, and 0 (− 1, 21) vs 0 (− 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008).ConclusionsWe reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results
AU  - Fish,M
AU  - Rynne,J
AU  - Jennings,A
AU  - Lam,C
AU  - Lamikanra,AA
AU  - Ratcliff,J
AU  - Cellone-Trevelin,S
AU  - Timms,E
AU  - Jiriha,J
AU  - Tosi,I
AU  - Pramanik,R
AU  - Simmonds,P
AU  - Seth,S
AU  - Williams,J
AU  - Gordon,AC
AU  - Knight,J
AU  - Smith,DJ
AU  - Whalley,J
AU  - Harrison,D
AU  - Rowan,K
AU  - Harvala,H
AU  - Klenerman,P
AU  - Estcourt,L
AU  - Menon,DK
AU  - Roberts,D
AU  - Shankar-Hari,M
DO  - 10.1007/s00134-022-06869-w
EP  - 1538
PY  - 2022///
SN  - 0342-4642
SP  - 1525
TI  - Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial
T2  - Intensive Care Medicine
UR  - http://dx.doi.org/10.1007/s00134-022-06869-w
UR  - https://link.springer.com/article/10.1007/s00134-022-06869-w
UR  - http://hdl.handle.net/10044/1/99786
VL  - 48
ER  -
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