Treatment with methyprednisolone improves clinical outcomes in nonintubated patients with severe Covid-19  pneumonia receiving high-flow oxygen therapy and baseline ferritin levels in the upper tertile, according to a study published in JAMA Network Open. 

The retrospective study published in JAMA Network Open included 380 nonintubated patients with severe Covid-19 on high-flow oxygen therapy hospitalized in an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020. These patients were administered systemic methylprednisolone. Mortality was considered as the primary outcome measure, while the secondary outcome points were a composite of death or mechanical ventilation at 28 days. The study aimed to examine if serum ferritin could be used as a possible marker of clinical response to methylprednisolone. Three tertiles of ferritin levels were defined: lower (29-619 ng/mL), middle (623-1316 ng/mL) and upper (1322-13 418 ng/mL). A total of 142 patients received methyprednisolone. 

Analysis of data revealed comparable ferritin levels in patients who received methylprednisolone vs those who did not; 992 ng/mL vs 893 ng/mL. However, in weighted analysis, a clinical benefit of methylprednisolone treatment was observed only in patients with baseline ferritin levels in the upper tertile (HR 0.16). In these patients, methylprednisolone was found to reduce mortality (80%) (hazard ratio [HR] 0.16) and also lower the risk of composite end point of death or mechanical ventilation at 28 days by 50% (HR 0.45). However, no such benefits were observed in patients with serum ferritin levels in the lower and middle tertiles. The mortality was higher in the middle (HR 2.46) and lower (HR 2.43) tertile groups. The composite end point rates with ferritin in the middle and lower tertiles were 0.83 and 0.89, respectively. 

Along with C-reactive protein (CRP), serum amyloid A, haptoglobin and fibrinogen, ferritin too is an acute phase reactant and a marker of inflammation. These inflammatory markers have gained prominence particularly during the ongoing Covid pandemic. The hyperinflammatory response is the hallmark of Covid-19. And, the degree of inflammation is reflected in the high ferritin levels (and other inflammatory markers), which may be also be predictive of mortality during hospitalization.

This study has demonstrated an association of serum ferritin levels and methylprednisolone treatment with outcomes in nonintubated patients with severe COVID-19. The study therefore suggests that “ferritin levels on admission may be used as a marker associated with corticosteroid response among patients with severe COVID-19 pneumonia”. It calls for further study to investigate if severe Covid-19 patients can be selected for steroid treatment based on the levels of inflammatory biomarkers.

Reference

1. Papamanoli A, et al. Association of serum ferritin levels and methylprednisolone treatment with outcomes in nonintubated patients with severe COVID-19 pneumonia. JAMA Netw Open. 2021 Oct 1;4(10):e2127172.