ABSTRACT
Background: COVID-19 has been recognized as an emerging and rapidly evolving health condition. For this reason, efforts to determine changes in laboratory parameters of COVID-19 patients as biomarkers are urgent. Lipids are essential components of the human body, and their modulation has been observed implicated in some viral infections. Methods: To evaluate the clinical diagnosis utility of the lipid profile changes in Mexican COVID-19 patients, the lipid profile of one hundred two COVID-19 positive patients from three hospitals in Culiacan, Sinaloa in northwest Mexico, was analyzed. ROC curves and binary logistic regression analysis were used as a predictive model to determine their clinical diagnostic utility. Results: Significant changes in the serum lipid profile of patients with COVID-19, such as low levels of cholesterol, LDL, and HDL, while high triglycerides and VLDL were observed. The same abnormalities in the lipid profile among non-critical and critical COVID-19 patients were detected. The predictive model analysis suggests that cholesterol and LDL have AUC values of 0.710 and 0.769, respectively, for COVID-19 (p= 0.0002 and p= <0.0001), and LDL low levels might be a risk factor for critical COVID-19 (OR= 2.07, 95% IC: 1.18 to 3.63; p= 0.01). Conclusion: Our findings suggest that low cholesterol and LDL levels could be considered an acceptable predictor for COVID-19, and low levels of LDL might be a risk factor for critical COVID-19 patients.
Subject(s)
COVID-19 , Virus DiseasesABSTRACT
Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1 and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs. One Sentence Summary / Running titleSuppression of coronavirus replication through thapsigargin-regulated ER stress, ERQC / ERAD and metabolic pathways