As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125,048 people worldwide, with a mortality rate of approximately 3.7% , compared to a lower influenza mortality rate. at 1% .
There is an urgent need for effective treatment.
The current focus has been on the development of new therapies, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 may have cytokine storm syndrome . We recommend identification and treatment of hyperinflammation using existing approved therapies with proven safety profiles to address the immediate need to reduce rising mortality.
Current COVID-19 treatment is supportive, and respiratory failure due to acute respiratory distress syndrome (ARDS) is the leading cause of mortality.
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As during previous pandemics (severe acute respiratory syndrome and Middle East respiratory syndrome), corticosteroids are not routinely recommended and may exacerbate lung injury associated with COVID-19.
However, in hyperinflammation, immunosuppression is likely to be beneficial.
Reanalysis of data from a phase 3 randomized controlled trial of IL-1 blockade (anakinra) in sepsis showed a significant survival benefit in patients with hyperinflammation, without major adverse events.
A multicenter randomized controlled trial of tocilizumab (IL-6 receptor blockade, licensed for cytokine release syndrome), in patients with COVID-19 pneumonia and elevated IL-6, was approved in China (ChiCTR2000029765). Inhibition of Janus kinase (JAK) 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., increased ferritin, decreased platelet count, or erythrocyte sedimentation rate) and HScore (table) to identify 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.
- The Hscore generates a probability of the presence of secondary HLH.
- HS scores greater than 169 are 93% sensitive and 86% specific for HLH.
- Note that bone marrow hemophagocytosis is not mandatory for the diagnosis of HLH.
HS scores can be calculated using an online HScore calculator. HLH = hemophagocytic lymphohistiocytosis. *(1) Defined as a hemoglobin concentration of 9 2 g/dL or less (≤5 71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or a platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. (2) HIV positive or receiving long-term immunosuppressive therapy (i.e., glucocorticoids, cyclosporine, azathioprine).
Author statements:
PM is a clinical training fellow within the Experimental Medicine Initiative to Explore New Therapies network and receives project funding unrelated to this Correspondence. PM is also co-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre, University Hospitals London. DFM chairs the Medical Research Council and NIHR COVID-19 funding committee for therapies and vaccines. DFM reports personal ARDS consulting fees for GlaxoSmithKline, Boehringer Ingelheim and Bayer; Additionally, his institution has received grant funding from the UK NIHR, Wellcome Trust, Innovate UK and others, all unrelated to this correspondence. DFM also has a patent issued to its institution for a treatment for ARDS. DFM is Director of Research at the Intensive Care Society and Director of the NIHR Efficacy and Mechanism Evaluation Programme. All other authors declare no competing interests.
