Inhaled Corticosteroids

Inhaled corticosteroids for the treatment of COVID-19

Why are inhaled corticosteroids important for the treatment of COVID-19?

COVID-19 predominantly affects the airways and lungs. The immune system fights the virus, causing inflammation of the lungs and airways. Due to inflammation, the lungs can become ineffective in removing carbon dioxide and moving oxygen back into the blood, causing breathing difficulties. More effective treatment options are needed for asymptomatic SARS‐CoV‐2 infection (virus that causes COVID‐19) and mild, moderate, or severe COVID‐19. Inhaled corticosteroids are medications breathed into the lower airways via inhalers, reducing lung inflammation. Inhaled corticosteroids may be effective in reducing COVID-19 symptoms and decreasing the risk of hospitalizations and death. 

Do inhaled corticosteroids work for the treatment of COVID-19?

  • Up to 30 days, inhaled corticosteroids may have little to no impact on death from any cause
  • Up to 30 days, inhaled corticosteroids likely decrease the risk of hospitalization or death 
  • Inhaled corticosteroids may reduce the time it takes for symptoms to resolve & likely stops COVID-19 symptoms at day 14
  • Inhaled corticosteroids may result in little to no impact in the number of adverse side effects or infections; there is not enough research to confirm if they cause serious harms
  • No data has been collected for people with asymptomatic COVID-19 or for those with moderate‐to‐severe COVID‐19

Equity: Do inhaled corticosteroids work in the disadvantaged?

  • All the studies were conducted in high-income countries, therefore impact on populations in low or middle income countries was not studied
  • One of the three included studies undertook extensive community outreach to increase participation from ethnic minority and socially deprived communities
  • Due to insufficient data, it was not possible to conduct subgroup analysis for certain sociodemographic characteristics (ex. age, ethnicity, sex) or comorbidites, as originally intended
  • There was no information for how to treat people with asymptomatic COVID-19, which could be especially important in areas with limited medical resources

Intervention Delivery

  • Intervention- any type or dose of inhaled corticosteroids
  • Comparisons- inhaled corticosteroids plus standard care versus standard care (with or without placebo)
  • Standard care had to be similar in both arms
  • A total of 1057 participants were analyzed in the inhaled corticosteroid arm (budesonide: 860 participants; ciclesonide: 197 participants), and 1075 participants in the control arm

Population and Setting

  • 3 randomized controlled trials (RCTs) evaluated inhaled corticosteroids for mild diagnosis of COVID‐19
  • Participants were included irrespective of age, sex or ethnicity
  • Participants had to have received at least 1 dose of a COVID-19 vaccination
  • Participants were not allowed to already be using inhaled corticosteroids
  • These studies analyzed 2171 participants older than 50 years with other medical problems consisting of 52% females, of whom 1057 received inhaled corticosteroids
  • Conducted in outpatient settings
  • Excluded studies examining nasal or topical steroids
  • 10 ongoing studies and 4 completed studies were found without published results. The findings of these studies are expected to be incorporated into future versions of the review
  • The studies were conducted in the United States and United Kingdom 

Summary of findings table: Inhaled corticosteroids plus standard care compared to standard care (with or without placebo) for adults with a confirmed diagnosis of mild COVID‐19

Patient or population: adults with a confirmed diagnosis of mild COVID‐19, of whom only 10% (219/2132) participants had received ≥ 1 vaccination                                

Settings: outpatient

Intervention: inhaled corticosteroids plus standard care

Comparison: standard care (with or without placebo)

 

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Certainty of the evidence
(GRADE)

 

Risk with standard care (with or without placebo) 

Risk with inhaled corticosteroids (plus standard care)

 

 

 

All‐cause mortality

Follow‐up: at up to 30 days

9 per 1000

3 fewer per 1000

(from 7 more to 7 fewer)

RR 0.61

(0.22 to 1.67)

2132

(3 RCTs)

Low

Admission to hospital or death

Follow‐up: at up to 30 days

79 per 1000

 

22 fewer per 1000

(from 1 to 39 fewer)

 

RR 0.72

(0.51 to 0.99)

 

2025

(2 RCTs)

Moderate

Symptom resolution: all initial symptoms resolved 

at day 14

465 per 1000

68 more per 1000

(from 42 to 140 more)

RR 1.19

(1.09 to 1.30)

 

1986

(2 RCTs)

         

Moderate

Symptom resolution: duration to symptoms resolved 

Follow‐up: at up to day 30

The mean duration to        symptoms resolved was  12.00 days.

The mean duration of symptoms resolved was 4 days earlier (from 1.78 to 6.22 earlier)

MD −4.00 days

(−6.22 to −1.78)

139

(1 RCT)

Low

Serious adverse events

Follow‐up: during study period

5 per 1000

2 fewer per 1000

(from 5 fewer to 9 more)

RR 0.51

(0.09 to 2.76)

1586

(1 RCT)

Very Low

Adverse events

Follow‐up: at up to day 30

143 per 1000

 

32 fewer per 1000

(from 24 fewer to 44 more)

 

RR 0.78

(0.47 to 1.31)

 

400

(1 RCT)

Low

Infections

Follow‐up: during study period

34 per 1000

 

4 fewer per 1000

(from 10 fewer to 55 more)

 

RR 0.88

(0.30 to 2.58)

 

400

(1 RCT)

Low

CI=confidence interval

MD=mean difference

RR= risk ratio

 

 

About quality of evidence (GRADE)
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.  
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.  
Low quality: Confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

 

Relevance of the review for disadvantaged communities

Findings

Interpretation
Equity - Which of the PROGRESS groups examined

 

Most of the participants of the study were adults aged 50 years and older with a mild diagnosis of COVID-19, consisting of 52% females. The review was carried out without excluding studies based on ethnicity, sex, disease severity or setting. One of the three included studies took extensive outreach to include participants of ethnic minority and socially deprived communities. 

 

The results of this review are primarily applicable to adults aged 50 years and older with mild diagnosis of COVID-19.  There is no evidence to confirm effectiveness of inhaled corticosteroids for people with asymptomatic, moderate or severe diagnosis of COVID-19. Low-certainty evidence shows that inhaled corticosteroids have little to no impact on death from any cause. Moderate-certainty evidence shows inhaled corticosteroids reduce risk of hospitalization or death and may reduce the time it takes for symptoms to solve  and stop at day 14. Low-certainty evidence suggests inhaled corticosteroids may have little to no impact in the number of infections of adverse events. 

Equity Applicability

 

The participants in the included studies were exclusively from higher income countries; USA and United Kingdom. The relevance of inhaled corticosteroids for people with mild diagnosis of COVID-19 was not considered for low and middle-income countries.

 

 

The results of the review are likely transferable to other high-income countries. The results may not apply for low and middle income countries. 

Cost-equity

The review does not comment on the cost-effectiveness of inhaled corticosteroids for the treatment of COVID-19

 

Policymakers planning should consider the potential tension the decision to use inhaled corticosteroid for COVID-19 treatment will have on the accessibility of inhaled corticosteroids, and how that will affect individuals who rely on the medication for other medical conditions such as asthma.

Cost-effectiveness of inhaled corticosteroids in low & middle income countries must also be considered-there may be limited access to these medications depending on cost. 

 
Monitoring & Evaluation for PROGRESS groups

 

Long-term evaluation of the effectiveness of inhaled corticosteroids for the treatment of COVID‐19 is needed. Other studies should examine the feasibility of implementing this intervention in low and middle-income countries.

 

This study evaluated the effects of inhaled corticosteroids for the treatment of mild          diagnoses of COVID-19 up to 30 days. Long-term follow up for the effectiveness of inhaled corticosteroids is encouraged to help determine is there are any serious long-term effects/harms. 

This summary is based on the following systematic review: 

Griesel M, Wagner C, Mikolajewska A, Stegemann M, Fichtner F, Metzendorf M-I, Nair AAnil, Daniel J, Fischer A-L, Skoetz N. Inhaled corticosteroids for the treatment of COVID-19. Cochrane Database of Systematic Reviews 2022, Issue 3. Art. No.: CD015125. DOI: 10.1002/14651858.CD015125.

Link for PDF: Inhaled corticosteroids for COVID-19.pdf

Comments on this summary? Please contact Jennifer Petkovic.                                                                                                                                                            This summary was prepared by Jessica Tiilikainen.