key: cord-257696-ybu772zw
authors: Bartoletti, Michele; Marconi, Lorenzo; Scudeller, Luigia; Pancaldi, Livia; Tedeschi, Sara; Giannella, Maddalena; Rinaldi, Matteo; Bussini, Linda; Valentini, Ilaria; Ferravante, Anna Filomena; Potalivo, Antonella; Marchionni, Elisa; Fornaro, Giacomo; Pascale, Renato; Pasquini, Zeno; Puoti, Massimo; Merli, Marco; Barchiesi, Francesco; Volpato, Francesca; Rubin, Arianna; Saracino, Annalisa; Tonetti, Tommaso; Gaibani, Paolo; Ranieri, Vito Marco; Viale, Pierluigi; Cristini, Francesco
title: Efficacy of corticosteroid treatment for hospitalized patients with severe COVID-19: a multicenter study
date: 2020-09-22
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.09.014
sha: 
doc_id: 257696
cord_uid: ybu772zw

OBJECTIVES: To assess the efficacy of corticosteroids in patients with coronavirus disease 2019 (COVID-19) METHODS: Multicenter observational study from February 22 through June 30, 2020. We included consecutive adult patients with severe COVID-19 defined as respiratory rate ≥30 breath per minute, oxygen saturation ≤93% on ambient air or arterial partial pressure of oxygen to fraction of inspired oxygen ≤300 mmHg. We excluded patients treated with other immunomodulant drugs, receiving low dose of corticosteroids and those receiving corticosteroids after 72h from admission. The primary endpoint was 30-day mortality form hospital admission. The main exposure variable was corticosteroid therapy at dosage of ≥0.5 mg/kg of prednisone equivalents. It was introduced as binomial covariate in a logistic regression model for primary endpoint and inverse probability of treatment weighting using the propensity score. RESULTS: Of 1717 patients with COVID-19 evaluated, 513 patients were included in the study; of these 170 (33%) were treated with corticosteroids. During the hospitalization 166 (34%) patients reached the primary outcome [60/170 (35%) in the corticosteroid group and 106/343 (31%) in the non-corticosteroid group]. At multivariable analysis corticosteroid treatment was not associated with lower 30-day mortality rate [aOR 0.59 (0.20-1.74), p=0.33]. After inverse probability of treatment weighting, corticosteroids were not associated to lower 30-day mortality [average treatment effect 0.05 (95% -0.02 to 0.09), p=0.12]. However, subgroup analysis revealed that in patients with PO(2)/FiO(2) < 200 mmHg at admission [135 patients, 52 (38%) treated with corticosteroids] corticosteroid treatment was associated to a lower risk of 30-day mortality [23/52 (44%) vs 45/83 (54%), aOR 0.20 (95%CI 0.04 to 0.90), p=0.036]. CONCLUSION: Our study shows that the effect of corticosteroid treatment on mortality might be limited to critically ill COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus 73 disease 2019 (COVID-19) is characterized by significant morbidity and mortality. 74 The clinical spectrum of COVID-19 is broad with the majority of infected individuals 75 experiencing only a mild or subclinical illness, especially in the early phase of disease [1] . 76 However, approximately 14 to 30% of hospitalized patients diagnosed with COVID-19 77 develop a severe respiratory failure requiring intensive care [2] [3] [4] [5] . 78 It has been hypothesized that the main cause of illness progression is a cytokine storm East respiratory syndrome (MERS) infections failed to find a benefit of corticosteroids [8] . 85 Among COVID-19 patients, two randomized trials showed conflicting results [9, 10]. 86 The exposure variable was corticosteroid treatment, defined as treatment with any 119 corticosteroid drug at dosage of ≥0.5 mg/kg of prednisone equivalents initiated within 72h 120 from hospital admission; it was treated as a binomial variable in models. 121 The primary endpoint was 30-day mortality from hospital admission. The effect of steroid treatment on 30-day mortality in two ways. First, univariable and 170 multivariable logistic models were fitted. At multivariable models, clinically relevant 171 variables, and those with p<0.10 at univariable analysis, were included, with no further 172 selection. To take time-dependency of steroid treatment in the analysis, we expanded our 173 dataset with one observation per each day since symptom onset; for each day, a binary 174 indicator for steroid treatment in that day for that patient was created. Finally, time since 175 symptom onset was subsequently included in models as cubic splines interacting with the 176 steroid treatment indicator; to take into account the multiple records per patient, robust 177 variance was estimated clustering by patient.

As a secondary analysis, logistic models with augmented Inverse-Probability-Weighting 179 (IPW) on propensity score for receiving steroid were also fitted. Risk factors for 30-day 180 mortality, besides corticosteroid treatment, were age, diabetes, hypertension, chronic 181 kidney disease, respiratory rate, SOFA score, creatinine, and CRP. Variables contributing 182 to the propensity score of receiving steroid in our model were study site, calendar month 183 into the pandemic, age, CRP, days since symptoms onset (as cubic splines). Covariate (Table 2 and web-only supplementary table S1) , several factors were 214 associated to 30-day mortality. At multivariable analysis (Table 2) In this study we were not able to find a lower mortality rate among hospitalized patients 

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