Rapid Changes in Inflammation Biomarker Could Be Key Predictor of COVID-19 Outcomes

Researchers analyzing levels of inflammation, known to be associated with severity of illness, by looking at C-reactive protein (CRP) trends in hospitalized COVID-19 patients found that a rapid rise in CRP levels during the first 48-to-72 hours of hospitalization was predictive of subsequent respiratory deterioration and intubation, while steadier CRP levels were observed in patients whose condition remained stable.

The results, from a study population of 100 COVID-19 patients at the Brigham and Women’s Hospital (Boston, MA, USA) also provided insight into the underlying mechanisms at play in COVID-19 infections. In particular, an increase in a cytokine called IL-6 during the first 24-48 hours was correlated to CRP levels and the progression of the disease. Fifteen patients treated during this acute period with the drug tocilizumab, an IL-6 receptor, had rapid, sustained reductions in their CRP levels. In larger, randomized trials, tocilizumab was not shown to provide benefits to COVID-19 patients, although the researchers have suggested that this could be because the drug was not administered early enough to the subset of patients who stand to benefit most. Alternatively, while CRP is associated with IL-6, CRP can reflect other inflammatory pathways besides IL-6, so targeting other inflammatory cytokines or pathways besides IL-6 could be considered. The researchers hope that the findings will help front-line workers better understand the volatility of COVID-19 patients' conditions.

"We realized that whereas a single CRP lab value from hospital admission wasn't very practical as a predictor of who might get sicker, tracking the rate of change from Day 1 to Day 2 or 3 was a very powerful and very clinically predictive test," said corresponding author Edy Yong Kim, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at the Brigham. "Even though all of these patients looked clinically similar upon admission, as early as 24 hours after hospitalization, the immune systems of patients who would go on to the ICU multiple days later were already inflamed, as measured by these biomarkers."

"Even if you gave immunomodulatory drugs, which reduce rising inflammation, as early as Day 3 - which is pretty early for a clinical trial - that may already be too late," added Kim. "But here we have some evidence that a rise in inflammation directly drives respiratory failure, which implies that the immunomodulatory drugs might be able to prevent respiratory failure if given very, very early - as early as hospital Day 1 and 2."

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