Association Of Serum Ferritin Levels And Methylprednisolone Treatment With Outcomes In Nonintubated Patients With Severe Covid-19 Pneumonia

This cohort study examines serum ferritin levels as a potential biomarker associated with response to methylprednisolone among nonintubated patients with severe COVID-19 pneumonia.Question Is the acute phase protein serum ferritin an early marker associated with response to methylprednisolone in nonintubated patients with severe COVID-19 pneumonia? Findings In this cohort study including 380 nonintubated patients with severe COVID-19 pneumonia, methylprednisolone was associated with lower mortality and reduced rates of death or mechanical ventilation only in patients with admission ferritin levels in the upper tertile of values (1322-13418 ng/mL); in contrast, there was no association with benefit among those with lower ferritin values at baseline. Meaning These findings suggest that ferritin levels on admission may be used as a marker associated with corticosteroid response among patients with severe COVID-19 pneumonia.Importance Serum ferritin, an acute phase marker of inflammation, has several physiologic functions, including limiting intracellular oxidative stress. Whether the effectiveness of corticosteroids differs according to serum ferritin level in COVID-19 has not been reported. Objective To examine the association between admission serum ferritin level and methylprednisolone treatment outcomes in nonintubated patients with severe COVID-19. Design, Setting, and Participants This retrospective cohort study included patients with severe COVID-19 admitted to an academic referral center in Stony Brook, New York, from March 1 to April 15, 2020, receiving high-flow oxygen therapy (fraction of inspired oxygen, >= 50%). The outcomes of treatment with methylprednisolone were estimated using inverse probability of treatment weights, based on a propensity score comprised of clinical and laboratory variables. Patients were followed up for 28 days. Data were analyzed from December 19, 2020, to July 22, 2021. Exposures Systemic methylprednisolone administered per the discretion of the treating physician. Main Outcomes and Measures The primary outcome was mortality, and the secondary outcome was a composite of death or mechanical ventilation at 28 days. Results Among 380 patients with available ferritin data (median [IQR] age, 60 years [49-72] years; 130 [34.2%] women; 250 [65.8%] men; 310 White patients [81.6%]; 47 Black patients [12.4%]; 23 Asian patients [6.1%]), 142 patients (37.4%) received methylprednisolone (median [IQR] daily dose, 160 [120-240] mg). Ferritin levels were similar in patients who received methylprednisolone vs those who did not (median [IQR], 992 [509-1610] ng/mL vs 893 [474-1467] ng/mL; P = .32). In weighted analyses using tertiles of ferritin values (lower: 29-619 ng/mL; middle: 623-1316 ng/mL; upper: 1322-13 418 ng/mL), methylprednisolone was associated with lower mortality in patients with ferritin in the upper tertile (HR, 0.16; 95% CI, 0.06-0.45) and higher mortality in those with ferritin in the middle (HR, 2.46; 95% CI, 1.15-5.28) and lower (HR, 2.43; 95% CI, 1.13-5.22) tertiles (P for interaction < .001). Composite end point rates were lower with methylprednisolone in patients with ferritin in the upper tertile (HR, 0.45; 95% CI, 0.25-0.80) but not in those with ferritin in the middle (HR, 0.83; 95% CI, 0.50-1.39) and lower (HR, 0.89; 95% CI, 0.51-1.55) tertiles (P for interaction = .11). Conclusions and Relevance In this cohort study of nonintubated patients with severe COVID-19, methylprednisolone was associated with improved clinical outcomes only among patients with admission ferritin in the upper tertile of values.