Beneficial Effect of Corticosteroids in Preventing Mortality in Patients Receiving Tocilizumab to Treat Severe COVID-19 Illness

Rubio-Rivas, Manuel; Ronda, Mar; Padulles, Ariadna; Mitjavila, Francesca; Riera-Mestre, Antoni; Garcia-Forero, Carlos; Iriarte, Adriana; Mora, Jose M; Padulles, Nuria; Gonzalez, Monica; Solanich, Xavier; Gasa, Merce; Suarez, Guillermo; Sabater, Joan; Perez-Fernandez, Xose L; Santacana, Eugenia; Leiva, Elisabet; Ariza-Sole, Albert; Dallaglio, Paolo D; Quero, Maria; Soriano, Antonio; Pasqualetto, Alberto; Koo, Maylin; Esteve, Virginia; Antoli, Arnau; Moreno, Rafael; Yun, Sergi; Cerda, Pau; Llaberia, Mariona; Formiga, Francesc; Fanlo, Marta; Montero, Abelardo; Chivite, David; Capdevila, Olga; Bolao, Ferran; Pinto, Xavier; Llop, Josep; Sabate, Antoni; Guardiola, Jordi; Cruzado, Josep M; Comin-Colet, Josep; Santos, Salud; Jodar, Ramon; Corbella, Xavier

Introduction: On the basis of the preliminary report from the RECOVERY trial, the use of dexamethasone or alternative corticosteroids (CS) is currently recommended in severe COVID-19 patients requiring supplemental oxygen. However, last updated recommendations have not taken a position either for or against the use of other immunomodulators such as tocilizumab (TCZ), with or without CS, since results are still limited. Methods: From March 17 to April 7, 2020, a real-world observational retrospective analysis was conducted at our 750-bed university hospital to study the characteristics and risk factors for mortality in patients with severe COVID-19 treated with TCZ, with or without CS, in addition to standard of care (SOC). Data were obtained from routine clinical practice, stored in electronic medical records. The main outcome was all-cause in-hospital mortality. Results: A total of 1,092 COVID-19 patients were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186, 155 (83.3 %) patients were receiving non-invasive ventilation when TCZ, with or without CS was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (SD 4.3) and 4.3 days (SD 3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR=1.09, p<0.001), chronic heart failure (HR=4.4, p=0.003), and chronic liver disease (HR=4.69, p=0.004). The use of CS, in combination with TCZ, was the main protective factor against mortality (HR=0.26, p<0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. Conclusions: In severe COVID-19 patients receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in combined therapy with TCZ, was the main protective factor against in-hospital mortality.