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

Disclosures

BMC Pulm Med. 2022;22(368)

Conclusion

The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection reduced in-hospital mortality and the likelihood of receiving invasive mechanical ventilation in those with severe COVID-19 infection. Further well-designed randomized control trials are indicated to validate our findings.

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Acknowledgements
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Funding
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Availability of data and materials
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Declarations
Ethics approval and consent to participate
Approved by the Institutional Review Board of MacKay Memorial Hospital (approval no. 21MMHIS330e) and the need for written informed consent was waived. This study was performed in accordance with the Declaration of Helsinki.

Consent for publication
Not applicable.

Table 1. Baseline characteristics, treatment and hospital outcomes of COVID-19 patients treated with and without inhaled ciclesonide
	Ciclesonide group (n = 184)	No ciclesonide group (n = 85)	p value
Age, years	62.0 (55.0–71.0)	62.0 (50.8–74.5)	0.9261
Sex (Male/female)	99/85 (53.8%/46.2%)	43/42 (50.6%/49.4%)	0.6239
Co-morbidities
Hypertension	73 (39.7%)	34 (40.0%)	0.9596
Diabetes	53 (28.8%)	25 (29.4%)	0.9188
Cardiovascular disease	13 (7.1%)	7 (8.2%)	0.7343
Heart failure	2 (1.1%)	11 (12.9%)	< 0.0001
Chronic obstructive pulmonary disease	8 (4.3%)	4 (4.7%)	> 0.9999
Organ transplantation	0 (0.0%)	0 (0.0%)	NA
Chronic kidney disease	6 (3.3%)	17 (20.0%)	< 0.0001
Malignancy	10 (5.4%)	6 (7.1%)	0.6013
Duration from symptoms to admission, days	5.0 (2.0–8.0)	3.0 (1.0–7.0)	0.0030
Fever	126 (68.5%)	59 (70.2%)	0.7730
Shang's CSS score^a	2.0 (1.0–3.0)	2.0 (1.0–4.0)	0.1723
High risk Shang's CSS score^a	61 (34.1%)	37 (47.4%)	0.0431
Severe COVID-19 infection	118 (64.1%)	34 (40.0%)	0.0002
Treatment
Systemic corticosteroids	167 (90.8%)	47 (55.3%)	< 0.0001
Remdesivir	81 (44.0%)	24 (28.2%)	0.0138
Tocilizumab	54 (29.3%)	16 (18.8%)	0.0679
Enoxaparin	62 (33.7%)	25 (29.4%)	0.4858
Traditional Chinese medicine formula NRICM101	57 (31.0%)	6 (7.1%)	< 0.0001
Outcomes
In-hospital mortality	14 (7.6%)	20 (23.5%)	0.0003
Supplemental oxygen during hospitalization	156 (84.8%)	51 (60.0%)	< 0.0001
Mechanical ventilation	23 (12.5%)	12 (14.1%)	0.7144
Duration of fever, days	2.0 (1.0–3.0)	2.0 (1.0–4.0)	0.1381
Duration of hospital stay, days	12.0 (10.0–18.0)	13.0 (10.0–25.3)	0.0577

COVID-19 coronavirus disease 2019; NA not applicable; Shang's CSS Shang's COVID-19 scoring system
^aThere were 179 versus 78 patients available to calculated Shang's CSS risk score

Table 2. Univariate logistic regression analysis for in-hospital mortality
	Odds ratio	95% confidence interval	p value
Inhaled ciclesonide	0.2676	0.1276–0.5612	0.0005
Age	1.0789	1.0455–1.1133	< 0.0001
Sex, male	1.0071	0.4899–2.0700	0.9847
Hypertension	3.2353	1.5251–6.8631	0.0022
Diabetes	2.4803	1.1914–5.1637	0.0152
Cardiovascular disease	2.5287	0.8556–7.4738	0.0934
Heart failure	32.2222	8.2954–125.1619	< 0.0001
Chronic obstructive pulmonary disease	1.4063	0.2947–6.7103	0.6689
Chronic kidney disease	11.1074	4.3914–28.0950	< 0.0001
Malignancy	1.6526	0.4457–6.1276	0.4524
Severe COVID-19 infection	2.3622	1.0572–5.2780	0.0361
High risk Shang's CSS score	13.9931	4.7086–41.5847	< 0.0001
Systemic corticosteroids	4.6593	1.0810–20.0825	0.039
Remdesivir	1.6705	0.8112–3.4398	0.1638
Tocilizumab	4.5699	2.1703–9.6229	0.0001
Enoxaparin	1.5534	0.7436–3.2454	0.2413
Traditional Chinese medicine formula NRICM101	0.8287	0.3424–2.0056	0.6769

COVID-19: coronavirus disease 2019; Shang's CSS: Shang's COVID-19 scoring system

Table 3. Multivariate logistic regression model for in-hospital mortality
	Odds ratio	95% confidence interval	p value
Inhaled ciclesonide	0.2724	0.0847–0.8763	0.0291
Age	1.0504	1.0004–1.1030	0.0481
Hypertension	0.8023	0.2547–2.5272	0.7067
Diabetes	1.3944	0.4669–4.1644	0.5514
Heart failure	9.7668	1.8968–50.2903	0.0064
Chronic kidney disease	1.5271	0.3673–6.3503	0.5604
Severe COVID-19 infection	0.7866	0.2385–2.5938	0.6933
High risk Shang's CSS score	4.4695	1.1094–18.0056	0.0352
Systemic corticosteroids	2.1265	0.2778–16.2771	0.4675
Tocilizumab	8.0628	2.5079–25.9221	0.0005

COVID-19 coronavirus disease 2019; Shang's CSS Shang's COVID-19 scoring system

Table 4. Subgroup analysis according to disease severity and hospital outcomes between COVID-19 patients treated with and without inhaled ciclesonide
	Severe COVID-19 infection			Not severe COVID-19 infection
	Ciclesonide (n = 118)	No ciclesonide (n = 34)	p value	Ciclesonide (n = 66)	No ciclesonide (n = 51)	p value
Initiated supplemental oxygen after admission	Not applicable			38 (57.6%)	17 (33.3%)	0.0095
Mechanical ventilation	18 (15.3%)	11 (32.4%)	0.0259	5 (7.6%)	1 (2.0%)	0.2301
In-hospital mortality	8 (6.8%)	17 (50.0%)	< 0.0001	6 (9.1%)	3 (5.9%)	0.7296
	High Shang's CSS risk			Low Shang's CSS risk
	Ciclesonide (n = 61)	No ciclesonide (n = 37)	p value	Ciclesonide (n = 118)	No ciclesonide (n = 41)	p value
Initiated supplemental oxygen after admission	9 (14.8%)	8(21.6%)	0.3865	27 (22.9%)	9 (22.0%)	0.9027
Mechanical ventilation	9 (14.8%)	8 (21.6%)	0.3865	14 (11.9%)	4 (9.8%)	> 0.9999
In-hospital mortality	10 (16.4%)	16 (43.2%)	0.0037	2 (1.7%)	2 (4.9%)	0.2738