Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis

ABSTRACT

Objectives

The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019). We systematically reviewed mortality in COVID-19 patients with ARDS and the potential role of systemic corticosteroids in COVID-19 patients.

Methods

Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle–Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS.

Results

The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23–56%). The pooled mortality estimate for China was 69% (95% CI: 67–72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58–86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2–29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%).

Conclusions

The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients.

KEYWORDS:

• Acute respiratory distress syndrome
• coronavirus disease 2019
• corticosteroids
• mortality

Article highlights

• Severe bilateral pneumonia developing into acute respiratory distress syndrome (ARDS) is one of the determinant factors for increased mortality in coronavirus disease 2019 (COVID-19).

• This systematic review and meta-analysis of original studies and country-specific reports assessed the mortality among COVID-19 patients with ARDS and to review the potential role of corticosteroids in COVID-19.

• Relatively high mortality was found with COVID-19 associated ARDS which demands an aggressive therapeutic intervention to prevent deaths.

• Despite the concerns that corticosteroids may hamper virus clearance, the low dose corticosteroids appear to have a role in the management of severely ill COVID-19 patients.

6. Expert Opinion

The current COVID-19 pandemic adversely impacted upon economy and costed many lives across the world particularly in developed countries. One of the main causes of deaths in severely ill COVID-19 patients was ARDS, a result of uncontrolled inflammatory processes originating from the airways and the SARS-CoV-2 mediated cytokine storm. The mortality rate augmented due to the lack of an effective treatment led researchers to investigate the potential role of systemic corticosteroids to mitigate the cytokine storms in severely ill COVID-19 patients to prevent death. Indeed, this was initially received criticism and became controversial due to the obvious effects on corticosteroids on immunity and the potential for delayed viral clearance. The studies from previous viral outbreaks supported the notion that corticosteroid should not be used in COVID-19 patients due to the risks of delayed viral clearance. However, there was a dearth of high-quality data to evidence that the delayed viral clearance represents a significant prognostic factor of the disease, while patients deteriorated rapidly once cytokine storms developed, leading to ARDS mediated death. Therefore, the benefits of administration of systemic corticosteroids in severely ill COVID-19 patients outweighs the potential risk of delayed viral clearance.

Importantly, the role of systemic corticosteroids has been previously established before COVID-19 for the treatment of all-cause ARDS. Besides, extrapolation of data from patients with SARS observed the effectiveness of systemic corticosteroids among patients with severe illness. This systematic review provided further evidence of the effectiveness of low-dose corticosteroid therapy in reducing the risk of mortality in COVID-19 patients with severe course of illness including those who develop ARDS. Recently, the release of the results from a randomized controlled trial (RECOVERY [99]) on the use of dexamethasone demonstrated mortality benefits in a subset of COVID-19 patients receiving respiratory support, which supports the findings of this systematic review and meta-analysis, though the data from RECOVERY trial has yet to complete the peer-review process at the time of writing this article. Nevertheless, the current evidence supports the recommendations by the Society of Critical Care Medicine [100] in permitting the use of systemic glucocorticoids in patients with COVID-19 who have moderate-to-severe ARDS (patients with a partial arterial pressure of oxygen/fraction of inspired oxygen [PaO2: FiO2]<100 mmHg).

The worsening glycaemic control is anticipated with the systemic corticosteroids use in both diabetic and non-diabetic COVID-19 patients. Although, it is not in the scope of this systematic review to discuss the management of acute hyperglycaemia induced by systemic corticosteroids, we still foresee that the mortality benefits of corticosteroid therapy outweigh the risks of altered glycaemic control. Nevertheless, hyperglycaemia during hospitalization has been linked to a worse prognosis in COVID-19 patients, therefore, it is imperative that clinicians should be prepared to initiate or adjust insulin therapy based on the type of corticosteroid administered (i.e. either long- or short-acting), in order to maintain optimal glycaemic control during the course of treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

SSH and CSK conceived the content, retrieved the data, wrote the manuscript, and approved the final version. HAM, RA, FM, and STRZ reviewed the data, revised the manuscript, and approved the final version.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.