Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.64827
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Funding
- UK Research and Innovation COVID-19 Rapid Response Rolling Call [MR/V027638/1]
- Imperial College London Community Jameel and the Imperial President's Excellence Fund
- UK Research and Innovation UKRI Innovation Fellowship at Health Data Research UK [MR/S004068/2]
- Wellcome Trust Wellcome-Beit Prize Clinical Research Career Development Fellowship [206617/A/17/A]
- Wellcome Trust [212252/Z/18/Z]
- Auchi Renal Research Fund
- Medical Research Council [MC_UU_00002/13]
- Sidharth Burman endowment
- MRC [MR/S004068/2, MR/V027638/1, MC_UU_00002/13] Funding Source: UKRI
- Wellcome Trust [212252/Z/18/Z] Funding Source: Wellcome Trust
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Analysis of blood samples from ESKD patients with COVID-19 revealed protein markers associated with clinical severity, including epithelial damage, immune activation, and cell-cell interactions, providing potential drug targets.
End-stage kidney disease (ESKD) patients are at high risk of severe COVID-19. We measured 436 circulating proteins in serial blood samples from hospitalised and non-hospitalised ESKD patients with COVID-19 (n = 256 samples from 55 patients). Comparison to 51 non-infected patients revealed 221 differentially expressed proteins, with consistent results in a separate subcohort of 46 COVID-19 patients. Two hundred and three proteins were associated with clinical severity, including IL6, markers of monocyte recruitment (e.g. CCL2, CCL7), neutrophil activation (e.g. proteinase-3), and epithelial injury (e.g. KRT19). Machine-learning identified predictors of severity including IL18BP, CTSD, GDF15, and KRT19. Survival analysis with joint models revealed 69 predictors of death. Longitudinal modelling with linear mixed models uncovered 32 proteins displaying different temporal profiles in severe versus non-severe disease, including integrins and adhesion molecules. These data implicate epithelial damage, innate immune activation, and leucocyte-endothelial interactions in the pathology of severe COVID-19 and provide a resource for identifying drug targets.
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