Serum 25-hydroxycholesterol levels are increased in patients with coronavirus disease 2019

• DOI: 10.1016/j.jacl.2022.10.012
• Publication Date: 2022-11-06T06:20:08Z
• Authors: Takumi Asano; Tetsuji Wakabayashi; Yasuyuki Kondo; Kenta Okada; Daisuke Yamamuro; Yukiko Koga; Kiyonori Oka; Momoe Sakurai; Nagisa Sawayama; Manabu Takahashi; Hiroaki Okazaki; Ken Ebihara; Kensuke Minami; Yuji Morisawa; Shuji Hatakeyama; Masami Matsumura; Shun Ishibashi
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; Humans; Animals; COVID-19; Virus Replication; Antiviral Agents; Original Research; Cell Line; 3. Good health

25-hydroxycholesterol (25HC), produced by cholesterol 25-hydroxylase (CH25H) in macrophages, has been reported to inhibit the replication of viral pathogens such as severe acute respiratory syndrome coronavirus-2. Also, CH25H expression in macrophages is robustly induced by interferons (IFNs).To better understand the serum level increase of 25HC in coronavirus disease 2019 (COVID-19) and how it relates to the clinical picture.We measured the serum levels of 25HC and five other oxysterols in 17 hospitalized COVID-19 patients.On admission, 25HC and 27-hydroxycholesterol (27HC) serum levels were elevated; however, 7-ketocholesterol (7KC) levels were lower in patients with COVID-19 than in the healthy controls. There was no significant correlation between 25HC serum levels and disease severity markers, such as interferon-gamma (IFN-γ) and interleukin 6. Dexamethasone effectively suppressed cholesterol 25-hydroxylase (CH25H) mRNA expression in RAW 264.7 cells, a murine leukemia macrophage cell line, with or without lipopolysaccharide or IFNs; therefore, it might mitigate the increasing effects of COVID-19 on the serum levels of 25HC.Our results highlighted that 25HC could be used as a unique biomarker in severe COVID-19 and a potential therapeutic candidate for detecting the severity of COVID-19 and other infectious diseases.