CRP levels may help identify COVID-19 patients most likely to benefit or be harmed by glucocorticoids

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According to an observational study published in the Journal of Hospital Medicine, C-reactive protein (CRP) levels may play a role in helping to identify the subset of patients with coronavirus disease 2019 (COVID-19) who would benefit from glucocorticoid therapy.

“Our study extends the findings of the [as yet unpublished] RECOVERY trial in two important ways,” wrote Marla J. Keller, MD, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, and colleagues. “First, in addition to finding some patients who may benefit, we also have identified patient groups that may experience harm from treatment with glucocorticoids. This finding suggests choosing the right patients for glucocorticoid treatment is critical to maximize the likelihood of benefit and minimize the risk of harm. Second, we have identified patient groups who are likely to benefit (or be harmed) on the basis of a widely available lab test (CRP).”

A preliminary analysis from the RECOVERY study showed a reduced rate of mortality in COVID-19 patients randomized to dexamethasone, compared with those who received standard of care. The findings prompted the National Institutes for Health COVID-19 Treatment Guidelines Panel to recommend dexamethasone for those who require supplemental oxygen or mechanical ventilation.

To further investigate, Dr. Keller and colleagues compared outcomes in 1,806 patients hospitalised at Montefiore with COVID-19 between March 11 and April 13, 2020. One group of 140 patients (7.7%) was treated with glucocorticoids within 48 hours of hospital admission, while a control group of 1,666 patients did not receive glucocorticoid therapy. Glucocorticoid formulations included were prednisone, as well as dexamethasone, methylprednisolone and hydrocortisone. The treatment and control groups were similar except that glucocorticoid-treated patients were more likely to have chronic obstructive pulmonary disease, asthma, rheumatoid arthritis or lupus, or to have received glucocorticoids in the year prior to admission.

The primary outcome was a composite of in-hospital mortality or in-hospital mechanical ventilation. In total, there were 318 who met the primary outcome of death or mechanical ventilation, 270 of whom died and 135 of whom required mechanical ventilation. Overall, early use of glucocorticoids was not associated with in-hospital mortality or mechanical ventilation as a composite outcome or as separate outcomes in both unadjusted and adjusted models.

However, the authors noted “significant heterogeneity of treatment effect in the subgroups defined by CRP levels (P for interaction = .008).” Early glucocorticoid use and an initial CRP value ≥20 mg/dL was associated with a significantly reduced risk of mortality or mechanical ventilation in unadjusted (odds ratio, 0.23; 95% CI, 0.08-0.70) and adjusted (aOR, 0.20; 95% CI, 0.06-0.67) analyses. Conversely, glucocorticoid treatment in patients with CRP <10 mg/dL was linked to a significantly higher risk of mortality or mechanical ventilation in unadjusted (OR_, 2.64; 95% CI, 1.39-5.03) and adjusted (aOR_, 3.14; 95% CI, 1.52-6.50) analyses.

“CRP is markedly elevated in cytokine storm syndrome (CSS), and improved outcomes with glucocorticoid therapy in this subgroup may indicate benefit in this inflammatory phenotype. Patients with lower CRP are less likely to have CSS and may experience more harm than benefit associated with glucocorticoid treatment,” the authors said.

They pointed to the retrospective nature of their analysis, and the fact that it was conducted at a single center as among some of the study’s limitations, adding that more studies are needed to further clarify the role of CRP in guiding glucocorticoid therapy and to predict clinical response.