Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison

BACKGROUND: Cytokine storm is a marker of severity and severe mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia. Immunomodulatory treatments may reduce morbidity and mortality. OBJECTIVES: To determine whether a 7-day course of methylprednisolone (MP) administered with and without tocilizumab improves outcomes in patients with severe COVID-19 (SARS-CoV-2) pneumonia requiring oxygen therapy, relative to historical controls. STUDY DESIGN AND METHOD: In this randomized controlled study, patients hospitalized with severe COVID-19 at Rashid Hospital, Dubai, in June 2020 were randomized 1:1 to receive intravenous MP (40 mg twice daily for 7 days) with or without a single dose of intravenous tocilizumab (400 mg). While data from the control arm, consisting of patients administered usual care, were obtained through retrospective review of their electronic medical records. The patients in the three arms were matched by disease severity and inclusion and exclusion criteria. The primary outcomes were day 45 all-cause mortality after randomization, rate of admission to the intensive care unit (ICU), length of ICU stay, days on ventilators, and length of hospital stay. RESULTS: In total, 76 patients were recruited, including 23 treated with MP, 26 with MP plus tocilizumab, and 27 historical controls. The rates of admission to the ICU and invasive mechanical ventilation were lowest in patients treated with MP alone, with the rates in this group being significantly lower than the rates in the control group (p = 0.04). Time on a ventilator was lowest in the MP group (1.09 ± 3.68 days) and highest in the control group (7.93 ± 14.86 days). The number of days in the ICU was significantly lower in the MP group than in the control and MP plus tocilizumab groups (p = 0.043). One patient (4.3%) in the MP group and five (18.5%) in the control arm died within 45 days. Survival was highest in patients treated with MP alone, with the addition of tocilizumab not improving survival or any of the other outcomes significantly. INTERPRETATION/CONCLUSION: In patients with severe COVID-19 pneumonia on oxygen support, administration of MP daily for 7 days had reduced mortality at 45 days and was associated with significantly lower ICU admission and ventilation rates compared with usual. Adding tocilizumab to MP did not improve any of the studied outcomes significantly.