Clinical Benefits of Inhaled Ciclesonide for Hospitalized Patients With COVID-19 Infection

A Retrospective Study

Kuan-Chih Kuo; Chao-Hsien Chen; Chieh-Jen Wang; Jou-Chun Wu; Hsin-Pei Chung; Yen-Ting Chen; Yen-Hsiang Tang; Wen-Kuei Chang; Chang-Yi Lin; Chien-Liang Wu


BMC Pulm Med. 2022;22(368) 

In This Article

Materials and Methods

Study Design and Patient Selection

This study was a single-center, retrospective analysis. All patients admitted to Mackay Memorial Hospital with a diagnosis of COVID-19 from May 1st, 2021, to June 30th, 2021, were enrolled. The patients were eligible for inclusion if they: (1) were ≥ 18 years of age, and (2) had a positive COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) at the emergency department. Patients who were (1) previously treated, (2) transferred to/from another hospital, (3) had delayed ciclesonide treatment (time from symptoms to first ciclesonide treatment > 14 days), and (4) received mechanical ventilation support on admission or within 24 h after admission, were excluded from the analysis. Their medical records were reviewed, and demographic characteristics, co-morbidities, treatment received, and outcomes during hospitalization were collected. Severe COVID-19 infection was defined as pulse oximetry < 94% under ambient air or requiring supplemental oxygen at admission.[38] Patients at high risk of mortality were defined according to Shang's COVID-19 scoring system (CSS) as > 2 points on the first day of admission.[39] This study was approved by the Institutional Review Board of MacKay Memorial Hospital (approval no. 21MMHIS330e) and the need for written informed consent was waived.

Treatment Protocol at our Hospital

After admission, all patients remained asymptomatic or had mild symptoms but did not require oxygen supply, only symptoms support measurements were applied. Pulse oximetry (SpO2) was monitored every 8 h in all patients. The patients with an FiO2 ≥ 0.4 were treated with oral dexamethasone 6 mg/day and remdesivir if within 5 days of symptom onset. Inhaled ciclesonide three puffs (480 mcg) every 8 h was an option if the patients needed oxygen supply. Prophylactic enoxaparin 40 mg SC daily was given if the D-dimer level was > 1000 ng/ml or there was a high risk of developing thromboembolism. Traditional Chinese medicine NRICM101 was also an option.

If the patient's condition continued to deteriorate and intubation with mechanical ventilator support was considered to be necessary, tocilizumab, an anti-IL-6 receptor antibody, was given (8 mg/kg of ideal body weight, maximum 800 mg) once. A prophylactic dose of enoxaparin was also given if not previously prescribed (Additional file: 1).

Outcome Measurements

The primary outcome was in-hospital mortality. The secondary outcomes included the use of supplemental oxygen, mechanical ventilation, duration of fever, and hospital stay. The time to mortality after admission was calculated, and the patients were followed until they died or were discharged.

Subgroup analyses by disease severity, including severe COVID-19 infection or risk according to Shang's CSS score, were also performed. The risks of supplemental oxygen, mechanical ventilation, duration of fever, and hospital stay were also analyzed.

Statistical Analysis

Categorical variables were reported as number (percentage). The chi-squared test or Fisher's exact test was used to compare the frequencies of categorical variables, when appropriate. Continuous variables with normal distribution were reported as mean ± standard deviation (SD), and non-normally distributed variables were reported as median (interquartile range [IQR]). The Shapiro–Wilk test was used to examine the normality of distribution of continuous variables. Two continuous normally distributed variables were compared using independent samples t-tests. The Mann–Whitney U test was used to compare two groups of non-normally distributed variables. For time-to-event analysis, the log-rank test and Cox's proportional hazards model were used to compare differences and effect size in the probability.

Variables with p < 0.05 in univariate logistic regression analysis were considered as confounders, and they were used in multivariable logistic regression analysis. All p values were two-sided, and a value < 0.05 was considered to be statistically significant. All analyses were performed using MedCalc version 20.014 for Windows (MedCalc Software Ltd, Ostend, Belgium).