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Authors: Giuseppe Gritti et al

Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.01.20048561v1

Journal/ Pre-Print: medRxiv

Key Words: siltuximab, interleukin-6, ARDS, C-Reactive Protein

Research Highlights

1. Observational case control study of use of siltuximab in COVID-19 patients with ARDs

2. 33% patients improved, 43% of patients stabilised and 24% experienced a worsening in their condition

3. CRP levels reduced to normal range following Siltuximab treatment

Summary

Trial of the use of siltuximab, a chimeric mAb that blocks IL-6, in COVID-19 patients who developed pneumonia/ARDS. Preliminary data presented for the first 21 patients treated with siltuximab and followed for up to 7 days show 33% (7/21) patients improved, 43% (9/21) of patients stabilised and 24% (5/21) experienced a worsening in their condition in which 1 patient died, and 1 patient experienced a cerebrovascular event. CRP levels returned to normal levels by day 5 in all patients with sufficient recorded values (100% 16/16). Targeting IL-6 has been identified as a potential strategy to mitigate the complications associated with COVID-19 infection.

Impact for SARS-CoV2/COVID19 research efforts

Treatment of SARS-CoV2/COVID19 positive individuals

Study shows potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection

Study Type

· Clinical Cohort study (e.g. drug trials)

Strengths and limitations of the paper

Novelty: Potential use of siltuximab to treat severe COVID-19 infected patients

Standing in the field: IL-6 may play a role in the cytokine storm associated with serious adverse outcomes in patients infected with SARS-CoV-2. Several studies are exploring blockade of IL-6 as a suitable therapeutic target for such patients.

Appropriate statistics: Not applicable

Viral model used: SARS-CoV2 strain

Translatability: Elevated IL-6 levels are associated with severity of disease and lead to ARDS the leading caused of mortality in patients with COVID-19. Direct targeting of IL-6 may improve clinical outcomes in these critically ill patients. Siltuximab is already an FDA-approved drug for other conditions.

Main limitations: Trial not randomised, no control arm, poor outcome, short follow-up period with limited number of patients. However, study is ongoing up to day 30 and further results expected.