Severe COVID-19 manifests as a viral-induced autoimmune multiorgan disease with pneumonia, and associated cytokine-mewdiated hyperinflammation and coagulopathy.1 A key proinflammatory cytokine involved in COVID-19 is interleukin-6 (IL-6), which induces synthesis of C-reactive protein (CRP) by hepatocytes.
We read with interest the observational study by Giovanni Guaraldi and colleagues,2 in which baseline concentrations of IL-6 and CRP, as well the PaO2/FiO2 ratio, were higher in patients who received tocilizumab compared with patients who received standard of care in the Modena cohort. Moreover, 76% of patients treated with tocilizumab received concomitant glucocorticoids.2 Preliminary unpublished data, from a Roche press release, regarding the COVACTA trial (NCT04320615) in severe COVID-19 pneumonia have revealed futility for tocilizumab compared with placebo for the primary end point after 4 weeks with no difference in mortality or need for ventilation.
Herold and colleagues3 reported on patients with severe COVID-19, showing that once IL-6 concentrations exceeded 80 pg/mL, the median time to mechanical ventilation was 1·5 days (range 0–4 days), and for CRP concentrations above 97 mg/mL, the median time to mechanical ventilation was 0 days (range 0–4 days). In another study,4 a composite score comprising SaO2/FiO2 ratio, and concentrations of CRP and IL-6 on admission, predicted clinical deterioration within 3 days of hospital admission, with an area under the receiver operating curve of 0·88.4
Another possibility for escalating treatment in patients with severe COVID-19 is to use medium-dose systemic glucocorticoids to non-selectively suppress the cytokine cascade. In one study,5 treatment with dexamethasone at 6 mg/day in 2014 patients, compared with usual care in 4321 patients, resulted in a 35% relative reduction in mortality in ventilated patients and a 20% relative reduction in patients requiring oxygen alone.
Taken together, these observations suggest that it is time to adopt a personalised endotype-driven approach to facilitate earlier identification of patients with COVID-19 who might benefit from such selective or non-selective cytokine suppression.
Acknowledgments
CRWK reports personal fees from AstraZeneca, Chiesi, and Circassia, outside the submitted work. BJL and RC declare no competing interests.
References
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