Abstract

Introduction: Dysregulated immune responses are implicated in the pathogenesis of severe COVID19 and may be modulated by the transcription factor Nrf2.

Hypothesis: Treatment with stabilised, synthetic sulforaphane (S-SFN)—an Nrf2 inducer—improves clinical status in hospitalised patients with suspected COVID19 pneumonia by curbing the inflammatory response.

Methods: Double-blind RCT of S-SFN (300mg, once daily, 14 days; EudraCT 2020-003486-19) in patients hospitalised with confirmed or suspected COVID19, in Dundee, UK. The primary outcome was the 7 point WHO Clinical Status scale at day 15. Blood samples were taken on days 1, 8 and 15 for measurement of 45 serum cytokines using the Olink Target48 panel. Key neutrophil functions were assessed including migration, phagocytosis and bacterial killing.

Results: 133 participants were randomized (placebo n=68, S-SFN n=65) from Nov 2020 to May 2021. S-SFN treatment did not improve clinical status at day 15 (adjusted OR 0.87 95%CI 0.41-1.83).

In serum, Nrf2 target TGFa was significantly increased at day 15 in those receiving S-SFN treatment compared with placebo (p=0.004; linear mixed effects model). Other targets implicated in cytokine storm, including IL6, IL1ß and TNFa, were unchanged. Patients receiving Tocilizumab (n=20) were excluded from exploratory analyses due to a strong impact upon IL6 levels, leading to significant increases at day 8 across the study population (p=0.015). S-SFN treatment did not significantly affect neutrophil function.

Conclusion: S-SFN treatment modulated select Nrf2 targets but did not modulate key cytokines. Further analyses to delineate drug activity are ongoing.