Introduction A growing evidence suggests that immune dysregulation and thrombotic phenomena are key features in the pathophysiology of COVID-19 . Apart from antivirals and respiratory support, anticoagulants, corticoids and immunomodulators are increasingly being prescribed, especially for more severe cases . We describe the clinical outcome of a large cohort of patients preferentially treated with glucocorticoids and interleukin inhibitors . Methods Single center and retrospective case series . Adult patients admitted with COVID-19 related respiratory insufficiency were included.Patients who died within 2 days after admission and those testing positive but asymptomatic were excluded . We defined two study periods: from March 3rd to March 31 st , 2020 (beginning of epidemic until peak of incidence) and April 1 st to May 7 th,2020 (second half of epidemic). The majority of patients received respiratory support, combinations of antimicrobials, anticoagulants, corticoids and interleukin inhibitors.Antivirals were preferentially given in the first period . The clinical outcome (death and ventilator dependency) of both periods was compared . Results From March 3 rd to May 7 th, 685 patients were included for analysis (58.4% males, mean age 68.9 years). Patients in the first period (n=408) were younger (66.6 vs 71.1 years, p=0.003), presented lower mean P a O 2/F i O2 ratio at admission (256.5 vs 270.4 mm Hg, p=0.0563), higher ferritin (1520 vs 1221 ng/ml, p=0.01), higher IL-6 (679 vs 194 pg/ml, p <0.0001) and similar D-dimer levels (3.59 vs 3.39 μg/mL, p=0.65) compared to the second period (n=277). Lopinavir/ritonavir and interferon were preferentially given in the first period (23.8% and 32% vs 1.8% and 11.9%, p <0.0001). Use of corticoids (88.2% vs 87.4%, p=0,74) and tocilizumab (26.29 vs 20.22% p=0.06) were similarly administered in both periods . Patients in the second period needed less mechanical ventilation (4.9% vs 16.9%, p <0.0001), fewer ICU admission (6.1% vs 20.1%, p <0.0001) and showed similar mortality (17.7% vs 15.4%, p=0.43). Infectious and thrombotic complications were comparable in both periods (both around 8%, with no statistical difference). Patients treated with tocilizumab (n=163) had lower mortality rate compared to those untreated under the same indication (7.9% vs 24.2%, p <0.0001) .Conclusions In this large retrospective COVID-19 in-hospital cohort, lopinavir/ritonavir and interferon showed no significant impact on survival . Extensive use of corticosteroids and tocilizumab resulted in good overall outcome and showed acceptable complication rates.