Another week, another COVID-19 study...

On August 12th, the Metcovid study was e-published ahead of print in Clinical Infectious Diseases.  This was another study looking at steroids in COVID-19 pneumonia, this time performed in Brazil.  Metcovid was a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial which enrolled 416 patients at a single academic center for the evaluation of methylprednisolone (MP; 0.5 mg/kg BID x 5 days) vs placebo.  As with all COVID studies, Metcovid has some significant limitations, and some equivocal findings.  However, Metcovid was largely in line with RECOVERY and other trials looking at steroids in COVID-19, which lends it some face validity.  Metcovid found no significant difference in the primary outcome (mortality at day 28), but did find a difference in mortality in patients over 60 years old (a post-hoc analysis).  Metcovid was probably underpowered (sample size was based on a 50% reduction in mortality), and did have a very small trend towards reduced mortality in the MP group (37.1% vs 38.2%, p=0.629).

Bottom Line: 

• Steroids (methylprednisolone 0.5 mg/kg BID x 5 days in this case) may have some mild benefit in severe cases of COVID-19 pneumonia, especially in patients who are elderly or have more aggressive inflammatory responses (as measured by CRP here).  
• Steroids in COVID-19 may be associated with some theoretical downsides like reduced viral clearance, but are relatively safe.  Main side effect is the well known hyperglycemia induced by corticosteroids.
• When using steroids in COVID pneumonia, both to stick with the evidence and for theoretical pharmacologic reasons, it may make sense to use dexamethasone or methylprednisolone, as these medications have a higher glucocorticoid:mineralocorticoid activity ratio.  It is hypothesized that using high mineralocorticoid steroids (like cortisone or hydrocortisone) may lead to increased water retention, which could be deterimental in ARDS.  This is purely theoretical.
• There was a signal towards harm in younger and less sick patients in this study, and it probably remains prudent to reserve steroids for older, sicker COVID-19 pneumonia patients, similar to the RECOVERY trial.

References

Metcovid: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1177/5891816