Mid-Regional pro-Adrenomedullin (MR-proADM), C-Reactive Protein (CRP) and Other Biomarkers in the Early Identification of Disease Progression in COVID-19 Patients in the Acute NHS Setting (preprint)

Background: There is a lack of biomarkers validated for assessing clinical deterioration in COVID-19 patients upon presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of a range of biomarkers, including C-Reactive Protein (CRP) and Procalcitonin (PCT) and Mid-Regional pro-adrenomedullin (MR-proADM), and White Cell Count to support prediction of clinical outcomes. Methods: Adult patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via RT-qPCR were included. Biomarkers were measured in blood samples taken within 24 hours of admission and logistic regression and area under the receiver operating characteristic (AUROC) curves were used to predict disease progression. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, admission to critical care and non-invasive ventilation (NIV) use. Findings: A total of 135 adult patients were identified. Elevated levels of MR-proADM were shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and non-invasive ventilation, when controlling for covariates. Interpretation: The measurement of biomarkers, particularly MR-proADM and CRP in patients with confirmed COVID-19 infection upon admission to secondary care shows significant potential to support clinicians in the early identification of those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions and treatment.

C-reactive protein guided use of procalcitonin in COVID-19 (preprint)

Low procalcitonin (PCT) concentrations (<0.5ng/mL) can facilitate exclusion of bacterial co-infection in viral infections, including COVID-19. However, costs associated with PCT measurement preclude universal adoption, indicating a need to identify settings where PCT provides clinical information beyond that offered by other inflammatory markers, such as C-reactive protein (CRP) and white cell count (WCC). In an unselected cohort of 299 COVID-19 patients, we tested the hypothesis that PCT<0.5ng/mL was associated with lower levels of CRP and WCC. We demonstrated that CRP values below the geometric mean of the entire patient population had a negative predictive value for PCT<0.5ng/mL of 97.6% and 100% at baseline and 48 hours into admission respectively, and that this relationship was not confounded by intensive care admission or microbiological findings. CRP-guided PCT testing algorithms can reduce costs and support antimicrobial stewardship strategies in COVID-19.