key: cord-0764659-7y8fx8ob
authors: Chroboczek, Tomasz; Lacoste, Marie; Wackenheim, Chloe; Challan-Belval, Thibaut; Amar, Benjamin; Boisson, Thomas; Hubac, Jason; Leduc, Dominique; Masse, Colleen; Dechaene, Victor; Touhiri-Maximin, Laetitia; Megessier, Sandrine; Lassale, Camille
title: Corticosteroids in patients with COVID-19: what about the control group?
date: 2020-06-16
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa768
sha: b772795ed019446787520e3960d3b863a0774c75
doc_id: 764659
cord_uid: 7y8fx8ob

nan

A c c e p t e d M a n u s c r i p t Dear Editor.

Effect of corticosteroids in COVID-19 still needs to be examined [1] [2] [3] . In their article, Fadel et al. compared two groups of patients hospitalized with COVID-19, with over half of them receiving corticotherapy in both groups (68.2%, vs 56.8% p=0.094), but different median time between hospitalization and therapy initiation (2 days, IQR 1-3, vs 5 days , IQR 3-7). Negative evolution of the disease occurred less often in the early group (34.9 vs 54.3%, p=0.005). They conclude that corticotherapy may improve the evolution of COVID-19 [4] . To reach this conclusion, comparison of treated and untreated patients should have been made.

In our hospital, we investigated retrospectively all cases of confirmed COVID-19 requiring more than 3L of oxygen, in adult patients hospitalized between 10 March and 9 April, 2020. The outcome of interest was oro-tracheal intubation, and we aimed to study the effect of corticotherapy. The study received approval from our Ethics Committee, the patients were informed, and the study was declared to the National Comity for Informatics and Liberties. The independent contribution of the patient's characteristics to the risk of intubation was analyzed by logistic regression (Table) . In order to compute the average treatment effect (ATE) of corticotherapy on intubation, we calculated a propensity score (PS) of exposure to corticosteroids using a logistic regression model, including: age, sex, Charlson index>1, BMI>25 kg/m 2 , hypertension, time from initiation of symptoms to hospitalization>7 days, CRP>150 mg/L, oxygen>3L, treatment with hydroxychloroquine, and azithromycin. These variables include potential confounders (related to treatment and outcome) and prognosis of the outcome [5] . We used PS matching, matching 1:1 to the nearest neighbor with a caliper of 0.25, to estimate the ATE on intubation of a treatment in a population where all individuals have the same probability of receiving the treatment. As sensitivity analysis, we used inverse probability weighting with the PS.

Out of 70 cases, 35 (50%) required mechanical ventilation, due to respiratory failure. Corticotherapy affected the risk of intubation with a risk difference (ATE) of -47.1% (95%CI -71.8 to -22.5). Using inverse probability weighting, the ATE was similar: -47.5% (95%CI -70.0% to -25.0%). Among the 49 patients that did not receive corticosteroids, 32, i.e. 65%, were intubated. Based on these results, systematic corticotherapy may have resulted in 65% -47.1% =17.9%, i.e. 12 intubations overall. That would have lifted the pressure on the limited number of beds at the ICU unit.

Fadel et al. found that the effect of corticosteroid varies according to the timing of their administration.

In our study, mean duration of symptoms before hospitalization was 7.6 ± 4 days, and mean duration before

Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury

COVID-19: consider cytokine storm syndromes and immunosuppression

Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

Variable selection for propensity score models

Corticosteroid treatment of patients with coronavirus disease

Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China

A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t