Author: Denise Baez
Among hospitalised patients with coronavirus disease 2019 (COVID-19), increasing levels of C-reactive protein (CRP) during the first 48 hours of hospitalisation is a better predictor of respiratory decline than initial CRP levels or ROX indices, according to a study published in Cell Reports Medicine.
A review of data from the first 100 patients admitted to the Brigham and Women’s Hospital, Boston, Massachusetts, for COVID-19 infection found that among patients who were stable and did not require intubation at admission, elevated CRP values in the first 48 to 72 hours of hospital admission accurately distinguished patients who would develop progressive respiratory failure from patients who would remain stable throughout their hospital course.
CRP level at admission correlated with physiological measures of disease severity, including sequential organ failure assessment (SOFA) score, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), and interleukin-6 (IL-6).
All patients in the study presented to the hospital approximately 1 week after symptom onset. Only 1 patient required high-flow nasal cannula, but 45 were intubated and on mechanical ventilation at some point during their hospitalisation. Treatment strategies for patients included administration of hydroxychloroquine, remdesivir versus placebo as part of a clinical trial, or tocilizumab. The overall mortality rate was 24%.
“Similar to prior studies, we first compared patients who only required non-ICU [intensive care unit] care during their hospital course (floor) with patients who required ICU-level care at any point during their hospitalisation,” explained Alisa A. Mueller, MD, Brigham and Women’s Hospital, Boston, Massachusetts, and colleagues. “Initial levels of several inflammatory biomarkers, including CRP, D-dimer, and procalcitonin, were more elevated in patients requiring ICU-level care compared with patients who only required care on the floor.”
However, the researchers decided to go a step further an stratify patients according to the stability and severity of their respiratory failure: (1) mild, meaning they remained on room air or supplemental oxygen; (2) progressive, meaning they initially received room air or supplemental oxygen and then later required intubation or high-flow nasal cannula; or (3) severe, meaning they required intubation within 12 hours of admission.
In all patients, CRP levels peaked early within approximately 10 days of symptom onset; however, change in CRP <72 hours of admission was significantly different between patients with mild versus progressive COVID-19 (P = .009), whereas it was similar between patients with progressive and severe disease (P = .81).
Compared with patients with mild COVID-19, those with progressive disease had a more rapid increase in CRP levels drawn at 24 to 48 hours (182.0 ± 101 vs 97.6 ± 72 mg/L; P = 0.006) and 48 to 72 hours (190.1 ± 99 vs 90.2 ± 64 mg/L; P< .001) after admission.
The odds ratio of requiring advanced respiratory support was 16.9 (P = 0.01) when CRP values of greater than 300 mg/L was achieved within 72 hours of admission.
The researchers went on to test the prognostic utility of CRP levels in determining the need for advanced respiratory support using receiver operating characteristic curve analyses. The area under the curve for CRP changes on days 0 to 1 of admission was greater than that for the ROX indices on day 0 and day 1. Day 0 to 1 CRP and day 0 CRP were independently associated with a need for an advanced respiratory support.
“Our study suggests that examination of dynamic trends, rather that absolute value at admission, can lead to strong associations with prognosis despite only using a single laboratory value,” the authors wrote. “Our study suggests that trending CRP, a highly accessible tool for frontline clinicians compared to complicated scoring systems, has predictive value for respiratory failure among initially non-critically ill patients on the general medical floor.”
The authors noted that IL-6 was markedly elevated in patients who required ICU level care at any point during their hospitalisation compared with non-ICU patients, and that IL-6 levels did show a striking correlation to CRP. However, “the number of patients with IL-6 levels were limited, as this institution’s clinical guidelines did not endorse routine clinical measurement of IL-6 because results took over 48 hours to return,” the authors explained. “In many institutions, CRP levels result within several hours and can capture rapidly evolving clinical courses that cytokine assays, which take more than 1 to 2 days, cannot. These results supported the further investigation of CRP as a biomarker with mechanistic implications and potential practical clinical utility.”