Background: The COVID-19 outbreak challenges the Spanish health system since March 2020. Some available therapies (antimalarials, antivirals, biological agents) were grounded on clinical case observations or basic science data. The aim of this study is to describe the characteristics and impact of different therapies on clinical outcomes in a cohort of severe COVID-19 patients. Methods: In this retrospective, single-center, observational study, we collected sequential data on adult patients admitted to Hospital Universitario Quironsalud Madrid. Eligible patients should have a microbiological (positive test on RT-PCR assay from a nasal swab) or an epidemiological diagnosis of severe COVID-19. Demographic, baseline comorbidities, laboratory data, clinical outcomes, and treatments were compared between survivors and non-survivors. We carried out univariate and multivariate logistic regression models to assess potential risk factors for in-hospital mortality. Findings: From March 10th to April 15th, 2020, 607 patients were included. Median age was 69 years [inter-quartile range, {IQR} 22; 65% male). The most common comorbidities were hypertension (276 [46.94%]), diabetes (95 [16.16%]), chronic cardiac (133 [22.62%]) and respiratory (114 [19.39%]) diseases. 141 patients (23.2%) died. In the multivariate model the risk of death increased with older age (odds ratio, for every year of age, 1.15, [95% CI 1.11 - 1.2]), tocilizumab therapy (2.4, [1.13 - 5.11]), C-reactive protein at admission (1.07, per 10 mg/L, [1.04 - 1.10]), D-dimer > 2.5 mg/mL (1.99, [1.03 - 3.6]), diabetes mellitus (2.61, [1.19 - 5.73]), and the PaO2/FiO(2) at admission (0.99, per every 1 mmHg, [0.98 - 0.99]). Among the prescribed therapies (tocilizumab, glucocorticoids, lopinavir/ritonavir, hydroxychloroquine, cyclosporine), only cyclosporine was associated with a significant decrease in mortality (0.24, [0.12 - 0.46]; p<0.001). Interpretation: In a real-clinical setting, inhibition of the calcineurin inflammatory pathway, NF-kappa B, could reduce the hyperinflammatory phase in COVID-19. Our findings might entail relevant implications for the therapy of this disease and could boost the design of newclinical trials among subjects affected by severe COVID-19. (C) 2020 The Author(s). Published by Elsevier Ltd.