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Should Corticosteroids Be Used to Treat COVID-19 Hyperinflammation?

After determining in previous coronavirus outbreaks that corticosteroids might have done more harm than good, the World Health Organization has recommended against use of corticosteroids to treat COVID-19. A new study argues, however, that the drugs should play a role in the treatment of novel coronavirus patients with deadly hyperinflammatory syndrome. Here is more information.

LONDON — The World Health Organization has recommended against treating COVID-19 with corticosteroids, which were widely used during the outbreaks of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, unless indicated for another reason.

“A systematic review of observational studies of corticosteroids administered to patients with SARS reported no survival benefit and possible harms (avascular necrosis, psychosis, diabetes, and delayed viral clearance),” the WHO said in recent guidance.

Correspondence published this month in The Lancet argues, however, that there should be some exceptions to the rule.

Authors from UK’s HLH Across Specialty Collaboration point out that a subgroup of patients with severe COVID-19 appear to have a cytokine storm syndrome, adding, “We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality.”

While respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality, according to the article, “Secondary hemophagocytic lymphohistiocytosis (sHLH) is an under-recognized, hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections and occurs in 3.7–4.3% of sepsis cases.”

The condition is characterized by unremitting fever, cytopenias, and hyperferritinemia, with pulmonary involvement (including ARDS) occurring in about 50% of patients.

The authors point out that predictors of fatality from a recent retrospective, multicenter study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p<0·001) and IL-6 (p<0·0001) and suggests that mortality might be due to virally driven hyperinflammation.

Conceding that corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury, the authors emphasize, “However, in hyperinflammation, immunosuppression is likely to be beneficial. Re-analysis of data from a phase 3 randomized controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.”

The correspondence goes on to say that a multicenter, randomized controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), has been approved in patients with COVID-19 pneumonia and elevated IL-6 in China (ChiCTR2000029765). It adds that Janus kinase (JAK) inhibition could affect both inflammation and cellular viral entry in COVID-19.

“All patients with severe COVID-19 should be screened for hyperinflammation using laboratory trends (e.g., increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore to identify the subgroup of patients for whom immunosuppression could improve mortality,” the authors conclude. “Therapeutic options include steroids, intravenous immunoglobulin, selective cytokine blockade (e.g., anakinra or tocilizumab) and JAK inhibition.”

The recommendation about corticosteroids use is in Interim guidance from the WHO, entitled “Clinical Management of Severe Acute Respiratory Infection When Novel Coronavirus (2019-Ncov) Infection is Suspected.”