Effect of IL-6R blockade on plasma lipids and clinical outcomes among hospitalized patients with COVID-19 infection

• DOI: 10.1016/j.jlr.2024.100568
• Publication Date: 2024-05-23T17:20:44Z
• Authors: Kusha Mohammadi; Mark W. Sleeman; Anita Boyapati; Parnian Bigdelou; Gregory P. Geba; Sergio Fazio
• Keywords: Lipid Profile; Post-hoc analysis

Plasma lipid levels are modulated by systemic infection and inflammation; it is unknown whether these changes reflect inflammatory responses or caused directly pathogen presence. We explored the hypothesis that anti-inflammatory intervention via interleukin 6 receptor (IL-6R) blockade would influence plasma during severe evaluated association of with clinical outcomes. Sarilumab (monoclonal antibody blocking IL-6R) efficacy was previously assessed in patients coronavirus disease 2019 (COVID-19) (NCT04315298). This analysis determined strong reduction sarilumab COVID-19 pneumonia increasing severity (severe, critical, multisystem organ dysfunction) affected between day 1 7 study therapy. Baseline reflected presence acute infection, characterized very low HDL-C, LDL-C, moderately elevated triglycerides (TGs). Disease associated progressively more abnormal levels. At 7, median increased versus placebo group (HDL-C +10.3%, LDL-C +54.7%, TG +32% vs. HDL-C +1.7%, +15.4%, +8.8%, respectively). No significant outcomes observed. In conclusion, severe-to-critical causes profound depression only modestly responsive to anti-IL-6R intervention. Conversely, strongly IL-6R blockade, likely returning predisease set point. These results advance our understanding complex relationship serum lipids infection/inflammation suggest contagious driven not IL-6-mediated inflammation.