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) 

In This Article

Abstract and Introduction

Abstract

Background: The successful management of patients infected with coronavirus disease 2019 (COVID-19) with inhaled ciclesonide has been reported, however few studies have investigated its application among hospitalized patients.

Methods: This retrospective cohort study enrolled all adult patients admitted to our hospital with confirmed COVID-19 infection from May to June 2021. Critical patients who received mechanical ventilation within 24 h after admission and those who started ciclesonide more than 14 days after symptom onset were excluded. The in-hospital mortality rate was compared between those who did and did not receive inhaled ciclesonide.

Results: A total of 269 patients were enrolled, of whom 184 received inhaled ciclesonide and 85 did not. The use of ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and a trend of shorter hospital stay (12.0 (10.0–18.0) days vs. 13.0 (10.0–25.3) days, p = 0.0577). In subgroup analysis, the use of inhaled ciclesonide significantly reduced mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and in those with a high risk of mortality (16.4% vs. 43.2%, p = 0.0037). The use of inhaled ciclesonide also reduced the likelihood of receiving mechanical ventilation in the patients with severe COVID-19 infection. After multivariate analysis, inhaled ciclesonide remained positively correlated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% confidence interval: 0.087–0.8763, p = 0.0291).

Conclusions: The use of inhaled ciclesonide in hospitalized patients with COVID-19 infection can reduce in-hospital mortality. Further randomized studies in patients with moderate to severe COVID-19 infection are urgently needed.

Introduction

Coronavirus disease 2019 (COVID-19) has infected 404 million people and caused 5 million deaths worldwide.[1] Several treatment options have been introduced, including systemic corticosteroids,[2–4] remdesivir,[5] tocilizumab,[3,6] enoxaparin,[7] and traditional Chinese medicine formula NRICM101.[8] However, the effectiveness of these treatments is still under debate.

In the early months of the pandemic, Beurnier et al.[9] reported a lower prevalence of asthma patients hospitalized with COVID-19 compared to the general population. There are several possible explanations for this finding. First, patients with asthma have been reported to have lower expressions of angiotensin-converting enzyme 2 (ACE2), the putative viral entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[10] Second, chronic inflammation in asthmatic lungs caused by repeated epithelial insults may lead to a degree of immune tolerance, thereby restricting the development of the excessive inflammatory response in COVID-19.[11–13] Third, it may be related to a possible protective effect of inhaled corticosteroids (ICS).[9,14–16]

Anti-inflammatory medications, and especially corticosteroids,[3,4] have become popular in managing patients with severe COVID-19 infection since the RECOVERY trial.[17] However, excess anti-inflammation may be detrimental for patients with milder disease.[17] Compared with systemic corticosteroids, ICS have milder systemic effects,[18] and have been shown to be effective in shortening the time to recovery among patients with mild COVID-19 infection.[19,20] Moreover, some studies have reported that corticosteroids may have anti-viral effects,[21–24] and reduce the expressions of ACE-2 and TMPRSS2.[24] The successful management of patients with COVID-19 infection with inhaled ciclesonide has been reported,[25–27] however results from larger patient groups have been controversial or even suggested that ICS may be harmful.[28,29] Although growing evidence supports the potential role of ICS in the treatment of patients with mild COVID-19 infection and those who do not require hospitalization,[19,20,30–35] the use of ICS in hospitalized patients remains controversial.[36] In 2020, we once successfully treated a patient with severe COVID-19 infection using inhaled ciclesonide.[37] Considering the limited therapeutic options during the pandemic, our institution then included it as a possible treatment for COVID-19 infection. In this study, we retrospectively analyzed hospitalized COVID-19 patients during the first wave of the pandemic (2021) in Taiwan and compared the effect of inhaled ciclesonide between those who did and did not receive treatment.

processing....