Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial
| Autor: | Fish, Matthew, Rynne, Jennifer, Jennings, Aislinn, Lam, C, Lamikanra, A, Ratcliff, J, Cellone-Trevelin, S, Timms, E, Jeriha, Jakob, Tosi, I, Pramanik, R, Simmonds, P, Seth, Sohan, Williams, J, Gordon, A C, Knight, J, Smith, D J, Whalley, J, Harrison, D, Rowan, K, Harvala, H, Klenerman, P, Estcourt, L, Menon, D K, Roberts, D, Shankar-Hari, Manu |
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| Přispěvatelé: | NIHR, National Institute for Health Research |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Adult
Science & Technology Convalescent plasma sub-phenotypes Critical Illness Precision medicine COVID-19 1103 Clinical Sciences Critical Care and Intensive Care Medicine Subphenotypes Emergency & Critical Care Medicine 1117 Public Health and Health Services REMAP-CAP Immunoglobulin Domain UK Investigators Treatment Outcome Critical Care Medicine General & Internal Medicine convalescent plasma Humans Cytokines Life Sciences & Biomedicine COVID-19 Serotherapy Biomarkers |
| Zdroj: | Fish, M, Rynne, J, Jennings, A, Lam, C, Lamikanra, A, Ratcliff, J, Cellone-Trevelin, S, Timms, E, Jeriha, J, Tosi, I, Pramanik, R, Simmonds, P, Seth, S, Williams, J, Gordon, A C, Knight, J, Smith, D J, Whalley, J, Harrison, D, Rowan, K, Harvala, H, Klenerman, P, Estcourt, L, Menon, D K & Roberts, D & Shankar-Hari, M 2022, ' Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial ', Intensive Care Medicine, vol. 48, no. 11, pp. 1525-1538 . https://doi.org/10.1007/s00134-022-06869-w |
| Popis: | Purpose Benefit 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 . Methods We 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) . Results Unsupervised 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). Conclusions We 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 with COVID-19 immunotherapies. |
| Databáze: | OpenAIRE |
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