Exploratory analyses of leukocyte responses in hospitalized patients treated with ozanimod following a severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection

Abstract

Sphingosine-1-phosphate receptor 1 (S1P₁) ligands effectively reduce immunopathological damage in viral pneumonia models. Specifically, S1P₁ ligands inhibit cytokine storm and help preserve lung endothelial barrier integrity. We recently showed that the S1P receptor ligand ozanimod can be safely administered to hospitalized patients with coronavirus disease 2019 (COVID-19) exhibiting severe symptoms of viral pneumonia, with potential clinical benefits. Here, we extend on this study and investigate the impact of ozanimod on key features of the immune response in patients with severe COVID-19. We quantified circulating cytokine levels, peripheral immune cell numbers, proportions and activation status; we also monitored the quality of the humoral response by assessing anti-severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) antibodies. Our findings reveal that patients receiving ozanimod during acute SARS-CoV-2 infection exhibit significantly reduced numbers of circulating monocytes compared with those receiving standard care. Correspondingly, in the ozanimod-treated group, circulating levels of C-C motif ligand 2 (CCL2) were decreased. While treatment with ozanimod negatively impacted the humoral response to COVID-19 in unvaccinated patients, it did not impair the development of a robust anti-SARS-CoV-2 antibody response in vaccinated patients. These findings suggest that ozanimod influences key immune mechanisms during the acute phase of SARS-CoV-2 infection.

Keywords: COVID‐19; S1P; anti–SARS‐CoV‐2 antibodies; clinical trial; monocytes.