β-d-mannuronic acid (m2000) and inflammatory cytokines in covid-19; an in vitro study

Coronavirus disease of 2019 (covid-19) can be complicated by acute respiratory distress syndrome (ards) and may be associated with cytokine storm and multiorgan failure. anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (nsaids) can be used for this purpose. in this study, we evaluated the immunomodulatory effect of mannuronic acid (m2000), which is a novel nsaid, on covid-19-related cytokine storms. this study was conducted in vitro on blood samples of 30 covid-19 patients who presented with ards to a referral center. peripheral blood mononuclear cells (pbmcs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. m2000 was administered with the dosages of 25 μg/well and 50 μg/well after 4 hours of incubation at 37°c. the quantitative real-time polymerase chain reaction (qrt-pcr) was conducted to assess mrna gene expression. enzyme-linked immunosorbent assay (elisa) was performed to evaluate the supernatant pbmc levels of interleukin (il)-6, il-17, tumor necrosis factor (tnf)-α, and interferon (ifn)-γ. both mrna expression and the supernatant pbmc levels of il-17, tnf-α, il-6, and ifn-γ were decreased in pbmcs of covid-19 patients treated with m2000 compared with the control group. for the first time, it was observed that m2000 could be effective in alleviating the inflammatory cascade of covid-19 patients based on an in vitro model. after further studies in vitro and in animal models, m2000 could be considered a novel nsaid drug in covid-19 patients.