https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext
Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality.2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections3 and occurs in 3·7–4·3% of sepsis cases.4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients.5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α.6 Predictors of fatality from a recent retrospective, multicentre 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),2
suggesting that mortality might be due to virally driven hyperinflammation.
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As during previous pandemics (severe acute respiratory syndrome and Middle East respiratory syndrome), corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury. However, in hyperinflammation, immunosuppression is likely to be beneficial. 7Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.8 A multicentre, randomised 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).9 Janus kinase (JAK) inhibition could affect both inflammation and cellular viral entry in COVID-19.10
All patients with severe COVID-19 should be screened for hyperinflammation using laboratory trends (eg, increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore11 (table) to identify the subgroup of patients for whom immunosuppression could improve mortality. Therapeutic options include steroids, intravenous immunoglobulin, selective cytokine blockade (eg, anakinra or tocilizumab) and JAK inhibition.
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