Prolonged low-dose methylprednisolone in patients with severe COVID-19 pneumonia

Salton, Francesco; Confalonieri, Paola; Meduri, G Umberto; Santus, Pierachille; Harari, Sergio; Scala, Raffaele; Lanini, Simone; Vertui, Valentina; Oggionni, Tiberio; Caminati, Antonella; Patruno, Vincenzo; Tamburrini, Mario; Scartabellati, Alessandro; Parati, Mara; Villani, Massimiliano; Radovanovic, Dejan; Tomassetti, Sara; Ravaglia, Claudia; Poletti, Venerino; Vianello, Andrea; Gaccione, Anna Talia; Guidelli, Luca; Raccanelli, Rita; Lucernoni, Paolo; Lacedonia, Donato; Foschino Barbaro, Maria Pia; Centanni, Stefano; Mondoni, Michele; Davì, Matteo; Fantin, Alberto; Cao, Xueyuan; Torelli, Lucio; Zucchetto, Antonella; Montico, Marcella; Casarin, Annalisa; Romagnoli, Micaela; Gasparini, Stefano; Bonifazi, Martina; D’Agaro, Pierlanfranco; Marcello, Alessandro; Licastro, Danilo; Ruaro, Barbara; Volpe, Maria Concetta; Umberger, Reba; Confalonieri, Marco

BACKGROUND: In hospitalized patients with COVID-19 pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for ICU and mortality. METHODS: We conducted a multicenter, observational study to explore the association between exposure to prolonged, low-dose, MP treatment and need for ICU referral, intubation or death within 28 days (composite primary endpoint) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels. RESULTS: Findings are reported as MP (n=83) vs. control (n=90). The composite primary endpoint was met by 19 vs. 40 [adjusted hazard ratio (HR) 0.41; 95% confidence interval (CI): 0.24-0.72]. Transfer to ICU and need for invasive MV was necessary in 15 vs. 27 (p=0.07) and 14 vs. 26 (p=0.10), respectively. By day 28, the MP group had fewer deaths (6 vs. 21, adjusted HR=0.29; 95% CI: 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs. 17.5 ± 12.8; p=0.001). Study treatment was associated with rapid improvement in PaO(2):FiO(2) and CRP levels. The complication rate was similar for the two groups (p=0.84). CONCLUSION: In patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large RCT (RECOVERY trial) has been performed that validates these findings. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04323592