SECTION 1: Inhaled budesonide in COVID 19 

Key pathogenetic mechanism underlying COVID 19 disease progression

A dysregulated type I interferon response to SARS-CoV-2

Overproduction of proinflammatory cytokines 

Progression to severe COVID-19 and death

Controlling the excessive inflammatory response may prevent disease progression. 

Inhaled corticosteroids have been used in the treatment of several inflammatory respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD), to control dysregulated airway inflammation, with a good efficacy and safety profile.  

Study by Ramakrishnan and colleagues showed that an easily accessible therapeutic intervention is effective to prevent clinical deterioration  of COVID-19. 

Results of PRINCIPLE trial showed that inhaled budesonide improved time to recovery by a median 3 days when used to treat COVID-19 in people at higher risk of adverse outcomes in the community.

Inhaled corticosteroids have been succesfully used to downregulate the excessive inflammation in asthma and COPD.

In chronic airway diseases like asthma and COPD, inhaled corticosteroids lower the pulmonary expression of the SARS-CoV-2 viral entry receptor, angiotensin-converitng enzyme 2. 

Some inhaled corticosteroids inlcuding budesonide reduce or inhibit SARS-CoV-2 replication in vitro. 

Reference: 

Agusti A, Torres F, Faner R. Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19. The Lancet Respiratory Medicine. April 9, 2021. DOI: https://doi.org/10.1016/S2213-2600(21)00171-5

Ramakrishnan S, et al. The Lancet respiratory Medicine. April 9, 2021. DOI:https://doi.org/10.1016/S2213-2600(21)00160-0

PRINCIPLE Collaborative Group, Yu LM, Bafadhel M, Dorward J, et al. Inhaled budesonide for COVID 19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial. BMJ Yale. DOI: https://doi.org/10.1101/2021.04.10.21254672