RESUMO
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 â= â408) were younger (66.6 vs 71.1 years, p â= â0.003), presented lower mean P a O 2/F i O2 ratio at admission (256.5 vs 270.4 âmm Hg,p â= â0.0563), higher ferritin (1520 vs 1221 âng/ml, p â= â0.01), higher IL-6 (679 vs 194 âpg/ml, p â< â0.0001) and similar D-dimer levels (3.59 vs 3.39 âµg/mL, p â= â0.65) compared to the second period (n â= â277). Lopinavir/ritonavir and interferon were preferentially given in the first period (23.8% and 32% vs 1.8% and 11.9%, p â< â0.0001). Use of corticoids (88.2% vs 87.4%, p â= â0,74) and tocilizumab (26.29 vs 20.22% p â= â0.06) were similarly administered in both periods. Patients in the second period needed less mechanical ventilation (4.9% vs 16.9%, p â< â0.0001), fewer ICU admission (6.1% vs 20.1%,p â< â0.0001) and showed similar mortality (17.7% vs 15.4%, p â= â0.43). Infectious and thrombotic complications were comparable in both periods (both around 8%, with no statistical difference). Patients treated with tocilizumab (n â= â163) had lower mortality rate compared to those untreated under the same indication (7.9% vs 24.2%, p â< â0.0001). 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.
RESUMO
Background: COVID-19 has high mortality in hospitalized patients, and we need effective treatments. Our objective was to assess corticosteroid pulses influence on 60-days mortality in hospitalized patients with severe COVID-19, intensive care admission, and hospital stay. Methods: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y Leon, Spain (865.096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2 < 300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or died the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then we used a Cox regression model in the PSM group to consider factors affecting mortality. Findings: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. One hundred and twenty-four patients were on corticosteroid pulses, and 133 were not. 30{middle dot}3% (37/122) of patients died in the corticosteroid pulses group and 42{middle dot}9% (57/133) in the non-exposed cohort. These differences (12{middle dot}6% CI95% [8{middle dot}54-16{middle dot}65]) were statically significant (log-rank 4{middle dot}72, p=0{middle dot}03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5{middle dot}31, p=0{middle dot}021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0{middle dot}561, p= 0{middle dot}039). There were no significant differences in intensive care admission rate (p=0{middle dot}173). The hospital stay was longer in the corticosteroid group (p<0,001). Interpretation: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both exposed and non-exposed groups. Funding: There was no funding provided.
