Abstract
Background
C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and has been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalised with COVID-19 and determine the utility of CRP on admission for predicting inpatient mortality.
Methods
Data were collected between February 27th and 10th 10 June incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance (Harrell’s C and AIC).
Results
The test and validation cohort distribution of CRP was not affected by age and mixture models indicated a bimodal distribution. A threshold cut-off of CRP 40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable).
Conclusions:
The distributional characteristics of CRP indicated an optimal cut-off of 40 mg/L was found associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions, and advanced care planning.
C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and has been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalised with COVID-19 and determine the utility of CRP on admission for predicting inpatient mortality.
Methods
Data were collected between February 27th and 10th 10 June incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance (Harrell’s C and AIC).
Results
The test and validation cohort distribution of CRP was not affected by age and mixture models indicated a bimodal distribution. A threshold cut-off of CRP 40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable).
Conclusions:
The distributional characteristics of CRP indicated an optimal cut-off of 40 mg/L was found associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions, and advanced care planning.
| Original language | English |
|---|---|
| Pages (from-to) | 420-429 |
| Number of pages | 10 |
| Journal | International Journal of Epidemiology |
| Volume | 50 |
| Issue number | 2 |
| Early online date | 3 Mar 2021 |
| DOIs | |
| Publication status | Published - Apr 2021 |
Bibliographical note
Funding declarationThis study received no specific funding. The study was partially supported through the NIHR Maudsley Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust in partnership with King's College London (BC)
Keywords
- CRP
- COVID-19
- Bimodal
- Trimodal
- Mortality
- Prognostic marker
- Mixture Mode