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

## TL;DR

This study explores how ozanimod affects immune responses in hospitalized patients with severe COVID-19, finding it reduces monocytes and CCL2 levels, with mixed effects on antibody responses.

## Contribution

The study provides new insights into ozanimod's immune-modulating effects during acute SARS-CoV-2 infection in hospitalized patients.

## Key findings

- Ozanimod-treated patients had significantly reduced circulating monocytes compared to standard care.
- CCL2 levels were lower in patients receiving ozanimod.
- Ozanimod impaired humoral response in unvaccinated patients but not in vaccinated ones.

## 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.

In this exploratory study on the putative mechanisms of action of ozanimod in the modulation of severe coronavirus disease 2019 (COVID‐19), we found that patients receiving standard of care plus ozanimod had reduced circulating monocytes and C–C motif ligand 2 (CCL2) levels, compared with patients receiving standard of care alone. Moreover, while ozanimod appeared to mitigate the humoral response in unvaccinated patients, it did not hinder the development of a strong anti–severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) antibody in vaccinated individuals.