The Role of Inhaled Corticosteroids (ICS) in Critically Ill Patients With COVID-19: A Multicenter, Cohort Study

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) can boost the systematic inflammatory response in critically ill patients, causing a systemic hyperinflammatory state leading to multiple complications. In COVID-19 patients, the use of inhaled corticosteroids (ICS) is surrounded by controversy regarding their impacts on viral infections. This study aims to evaluate the safety and efficacy of ICS in critically ill patients with COVID-19 and its clinical outcomes. Method: A multicenter, noninterventional, cohort study for critically ill patients with COVID-19 who received ICS. All patients aged ≥ 18 years old with confirmed COVID-19 and admitted to intensive care units (ICUs) between March 1, 2020 and March 31, 2021 were screened. Eligible patients were classified into two groups based on the use of ICS ± long-acting beta-agonists (LABA) during ICU stay. Propensity score (PS)-matched was used based on patient’s Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, systemic corticosteroids use, and acute kidney injury (AKI) within 24 h of ICU admission. We considered a P-value of < 0.05 statistically significant. Results: A total of 954 patients were eligible; 130 patients were included after PS matching (1:1 ratio). The 30-day mortality (hazard ratio [HR] [95% confidence interval [CI]]: 0.53 [0.31, 0.93], P-value = 0.03) was statistically significant lower in patients who received ICS. Conversely, the in-hospital mortality, ventilator-free days (VFDs), ICU length of stay (LOS), and hospital LOS were not statistically significant between the two groups. Conclusion: The use of ICS ± LABA in COVID-19 patients may have survival benefits at 30 days. However, it was not associated with in-hospital mortality benefits nor VFDs.

Clinical benefits of inhaled ciclesonide for hospitalized patients with COVID-19 infection: a retrospective study

“…Two participants in the budesonide group and four in the usual care group had serious adverse events. In Al Sulaiman et al’s [ 36 ] study, the 30-day mortality rate was significantly lower in 65 patients who received ICS during ICU stay (HR: 0.53, 95% CI: 0.31–0.93, p = 0.03). However, in-hospital mortality, ventilator-free days, ICU and hospital length of stay were not statistically significant between the ICS and usual care groups.…”

“…However, only our study was performed in hospitalized, severe COVID-19 patients. Al Sulaiman et al [ 36 ] recruited a similar age group (61.4 ± 14.7 years) of patients in an ICU who mainly used inhaled budesonide, but only 30 days mortality was significant. Differences in the steroids used, dosage and study outcomes between the studies make direct comparisons impractical.…”

“…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 ].…”

“…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][31][32][33][34][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].…”

Inhaled therapy for COVID-19: Considerations of drugs, formulations and devices

“…An inhaled hydroxychloroquine can be effective in COVID-19 patients reducing side effects that are associated with oral dosage form ( de Reus et al, 2020 ). A multicentre, noninterventional, cohort study conducted over 954 critically ill COVID-19 patients showed that inhaled corticosteroids lowered the mortality rate which was statistically significant ( Al Sulaiman et al, 2022 ). In a randomized and open-label Phase 2 study over 61 milds to moderately affected COVID-19 patients, it was found that inhaled ciclesonide eradicated SARS-CoV-2 more compared to the standard care ( Song et al, 2021 ).…”