Abstract

Introduction: Previous randomized trials suggest the benefit of inhaled budesonide for COVID-19 patients in outpatient settings. We evaluated available studies on the effect of the therapeutic use of inhaled corticosteroids (ICS) on mortality and pertinent clinical outcomes. Methods: A comprehensive literature search was conducted across the WHO, LitCOVID, and EMBASE databases from inception until June 30th, 2022. The primary outcome was overall mortality and secondary outcomes included symptom-based clinical improvement rates at day 14, ER visits or hospitalization, and adverse events. Data analysis was performed using Review Manager Software, version 5.2, to evaluate the combined odds ratio (OR) with 95% confidence intervals (CI) using a random-effects model. Results: Nine studies (7 RCTs (3 budesonide, 3 ciclesonide, 1 fluticasone RCTs), & 2 observational studies) were included in the mortality meta-analysis. Of the 3,934 patients included, 103 patients died (44 out of 1925 in the ICS group and 59 out of 2009 in the non-ICS group). The odds of mortality in the therapeutic ICS use group were lower compared to the non-ICS therapy group (OR 0.78, 95% CI 0.48-1.28, p-value=0.33, I2=0%). The result was statistically insignificant, possibly due to the low mortality rate. But therapeutic ICS showed statistically significant clinical improvement rates at day 14 (5 RCTs; 3 Ciclesonide, 2 Budesonide) (OR 1.56, 95% CI 1.31-1.86, p < 0.0001, I2=0%). The number of ED visits/Hospitalization rate, and adverse events were not statistically significant between the groups (OR 0.73, 95% CI 0.32-1.70, p= 0.47 I2=75% and OR 1.10 95% CI 0.67-1.82, p=0.70, I2=28%). Conclusions: This meta-analysis shows that the therapeutic use of ICS in COVID-19 is associated with higher symptom-based clinical improvement rates. Although the reduction in mortality odds remained insignificant, as the overall mortality rates were low which increased the confidence interval overall. Early administration of ICS showed a trend towards the reduced likelihood of urgent care needs. Well-designed trials are needed to explore ICS efficacy in patients with a high risk of disease progression and in reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2.

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