Systemic Corticosteroids | Cochrane Equity

Systemic Corticosteroids slightly reduces all‐cause mortality in people hospitalized because of symptomatic COVID‐19

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Why is systemic corticosteroid treatment of COVID-19 important?

COVID-19 is an infectious disease that affects the lungs and airways. As the immune system fights the virus, the lungs and airways become inflamed, causing breathing difficulties. Corticosteroids are anti-inflammatory medicines given orally or by injection (systemic) that reduce redness and swelling. Some patients’ immune systems overreact to the virus causing further inflammation and tissue damage; corticosteroids may help to control this response.

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

Moderate‐certainty evidence shows that systemic corticosteroids slightly reduces all‐cause mortality in people hospitalised for symptomatic COVID‐19
Low‐certainty evidence suggests there may also be a reduction in ventilator‐free days with systemic corticosteroid use.

Equity: Do systemic corticosteroids work in the disadvantaged?

The study participants were mainly from high‐income countries. Only 13% of participants came from middle‐income countries and none from low‐income countries. In low and middle‐income countries, there might be a more severe shortage of hospital beds in both ordinary wards and intensive care units, shortage of oxygen and other resource constraints on the delivery of respiratory support, and other aspects of care labelled as standard care in this review

Intervention Delivery

All the completed studies included studies comparing systemic corticosteroids: hydrocortisone, prednisolone & methylprednisolone, and dexamethasone to standard care (plus/minus placebo), except one compared methylprednisolone to dexamethasone
The route of administration was predominately intravenous except one study allowed both oral and intravenous administration, and another performed oral dose-tapering after intravenous administration

Population and Setting

All participants were adults hospitalized with a suspected or confirmed diagnosis of COVID-19
The review was carried out without excluding any studies based on gender, ethnicity, disease severity, or setting
Studies that included populations with other coronavirus diseases were excluded
We included 11 studies, of which two were multi-centre platform RCTs, five were multi-centre RCTs, and four were single-centre RCTs
The study participants were mainly from high‐income countries. Only 13% of participants came from middle‐income countries and none from low‐income countries

Summary of Findings [SOF] Table: Systemic Corticosteroids plus standard care compared to standard care

for adults with suspected or confirmed diagnosis of COVID-19

Patient or population: Adults with suspected or confirmed diagnosis of COVID-19

Settings: Inpatient, ICU

Intervention: Systemic Corticosteroids plus standard care

Comparison: Standard care

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Certainty of the evidence (GRADE)
	Risk with standard care	Risk with systemic corticosteroids plus standard care
All cause mortality follow up: range 21 days to 60 days	275 per 1000	245 per 1000 (220 to 275)	RR 0.89 (0.80 to 1.00)	7930 (9 RCTs)	Moderate
Clinical improvement: Ventilator-free days follow up: 28 days	The mean clinical improvement: Ventilator-free days was 4 days	MD 2.6 days more (0.67 more to 4.53 more)	-	299 (1 RCT)	Low
RR=risk ratio CI=confidence interval MD= mean difference
About quality of evidence (GRADE) High quality (High): Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality (Moderate): Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality (Low): Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality (Very low): We are very uncertain about the estimate.

Relevance of the review for disadvantaged communities
Findings	Interpretation
Equity - Which of the PROGRESS groups examined
Participants in the study were adults hospitalised with a suspected or confirmed diagnosis of COVID-19. The review was carried out without excluding any studies based on gender, ethnicity, disease severity, or setting	Moderate‐certainty evidence shows that systemic corticosteroids slightly reduces all‐cause mortality in people hospitalised because of symptomatic COVID‐19. Low‐certainty evidence suggests that there may also be a reduction in ventilator‐free days.
Equity Applicability
The participants in the included studies were exclusively from higher income and upper middle-income countries. The circumstances of low-income countries were not considered.	In low- and middle-income countries, there might be a more severe shortage of hospital beds in both ordinary wards and intensive care units, shortage of oxygen and other resource constraints on the delivery of respiratory support, and other aspects of care labelled as standard care in this review. These factors could severely limit the accessibility of this intervention within low-and middle- income countries.
Cost-equity
The review does not comment on the cost-effectiveness of systemic corticosteroids for the treatment of COVID-19	Policymakers planning to endorse systemic corticosteroids as a form of treatment for COVID-19 need to consider the potential strain that the decision will have on the availability of systemic corticosteroids, and how that will affect individuals who rely on the medicine for other conditions such as rheumatoid arthritis. Cost-effectiveness of systemic 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

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

COVID-19 is a novel coronavirus, and its long-term effects are still relatively unknown, participants in this study should be monitored to evaluate the potential effects of this intervention.

Comments on this summary? Please contact Jennifer Petkovic.

This summary was prepared by Obinna Ikeonu.