Baseline levels of C-reactive protein (CRP) and the incidence and outcome of human sepsis

Hamilton, Fergus, Underwood, Jonathan ORCID: https://orcid.org/0000-0001-6963-2821, Woolley, Thomas ORCID: https://orcid.org/0000-0001-6225-5365, Timpson, Nicholas, Watson, Jessica, Fasham, James, Butler-Laporte, Guillaume, Ghazal, Peter ORCID: https://orcid.org/0000-0003-0035-2228 and Davey-Smith, George Baseline levels of C-reactive protein (CRP) and the incidence and outcome of human sepsis. Nature Communications Item availability restricted.

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Abstract

CRP is an evolutionarily conserved acute phase reactant believed to be critical for survival against infection. As a function of this, it is well known that circulating CRP levels can provide a valuable clinical measure of acute inflammatory illness. However, whether chronic levels influence infection outcomes in adults is not known. Using observational and genetic data from ~1,000,000 people we find evidence suggesting that lower chronic levels of circulating CRP protect against risk of sepsis and death from non-pneumococcal infections. We additionally identified 13 healthy homozygotes with a deleterious missense variant in CRP, suggesting redundancy. Furthermore, using nationally linked primary care and microbiological data analyses identified that CRP measured in primary care was associated with inflammatory response and mortality in subsequent bloodstream infection years later. Overall, our results suggest increasing infection pathology with increasing chronic levels of CRP. This has broad implications for early prevention and management of sepsis and non-communicable inflammatory diseases, suggesting interventions that reduce CRP may prevent and reduce the severity of future infection.

Item Type:	Article
Status:	In Press
Schools:	Schools > Mathematics Schools > Medicine
Subjects:	Q Science > QR Microbiology R Medicine > R Medicine (General)
Publisher:	Nature Research
ISSN:	2041-1723
Date of First Compliant Deposit:	11 September 2026
Date of Acceptance:	3 June 2026
Last Modified:	11 Sep 2026 15:26
URI:	https://orca.cardiff.ac.uk/id/eprint/189527

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