AUTHOR=Gong Jiao , Chen Yaqiong , Jie Yusheng , Tan Mingkai , Jiang Zhaofang , Yuan Lianxiong , Cao Jing , Li Ganwen , Chong Yutian , Qu Jiuxin , Shi Yaling , Hu Bo TITLE=U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=Volume 8 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.604736 DOI=10.3389/fcvm.2021.604736 ISSN=2297-055X ABSTRACT=Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protect against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including non-severe (n=460) and severe group (severe and critical cases) (n=141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in severe group was higher than non-severe group (22.7% vs 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C less than or equal to 1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p =0.023 ) and 2.02 (1.04–3.94; p =0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108–131mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p=0.035) and 2.36 (1.09–5.14; p=0.030). Similar results yielded using 0.3 mmol/L and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.