HDL cholesterol levels and susceptibility to COVID-19

Chidambaram, Vignesh; Kumar, Amudha; Majella, Marie Gilbert; Seth, Bhavna; Sivakumar, Ranjith Kumar; Voruganti, Dinesh; Bavineni, Mahesh; Baghal, Ahmad; Gates, Kim; Kumari, Annu; Al’Aref, Subhi J.; Galiatsatos, Panagis; Karakousis, Petros C.; Mehta, J. L.

doi:10.1016/j.ebiom.2022.104166

Cited by 21 publications

(18 citation statements)

References 45 publications

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“…Apo-A1, an important component of HDL, has been shown to inhibit virus fusion and its entry into the host cells. Taken together, these data support our findings that increased serum HDL-C levels may be protective against an SARS-CoV-2 infection [ 28 ].…”

Section: Covid-19 Diseases In Lipid Metabolism Pregnancy Womensupporting

confidence: 91%

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns

Jovandaric¹,

Dokić

Babovic

et al. 2022

IJMS

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Coronavirus disease (COVID-19) is an infectious disease caused by SARS-CoV-2. Elderly people, people with immunodeficiency, autoimmune and malignant diseases, as well as people with chronic diseases have a higher risk of developing more severe forms of the disease. Pregnant women and children can becomesick, although more often they are only the carriers of the virus. Recent studies have indicated that infants can also be infected by SARS-CoV-2 and develop a severe form of the disease with a fatal outcome. Acute Respiratory Distress Syndrome (ARDS) ina pregnant woman can affect the supply of oxygen to the fetus and initiate the mechanism of metabolic disorders of the fetus and newborn caused by asphyxia. The initial metabolic response of the newborn to the lack of oxygen in the tissues is the activation of anaerobic glycolysis in the tissues and an increase in the concentration of lactate and ketones. Lipid peroxidation, especially in nerve cells, is catalyzed by iron released from hemoglobin, transferrin and ferritin, whose release is induced by tissue acidosis and free oxygen radicals. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through various pathways, resulting in a decrease in the antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in the cells, ultimately leading to oxidative cell stress, and finally, death. Conclusion: damage to the mitochondria as a result of lipid peroxidation caused by the COVID-19 disease can cause the death of a newborn and pregnant women as well as short time and long-time sequelae.

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Section: Covid-19 Diseases In Lipid Metabolism Pregnancy Womensupporting

confidence: 91%

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns

Jovandaric¹,

Dokić

Babovic

et al. 2022

IJMS

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“…Specifically, a reduction of serum HDL-C in COVID-19 patients is linked with disease severity [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Moreover, patients with higher antecedent HDL-C levels have a lower risk of COVID-19 infection [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Low HDL Cholesterol Efflux Capacity Indicates a Fatal Course of COVID-19

et al. 2022

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Plasma membrane cholesterol is required for proper trafficking and localization of receptors that facilitate severe acute respiratory syndrome coronavirus 2 infection. High-density lipoproteins (HDL) mobilize plasma membrane cholesterol, and HDL-cholesterol levels are associated with the severity of COVID-19 disease and mortality. However, HDL-cholesterol levels poorly reflect the function of this complex family of particles, and a detailed assessment of COVID-19-associated changes in HDL functionality and its prognostic value is lacking. In the present study, we assessed HDL cholesterol efflux capacity, HDL anti-inflammatory and antioxidant properties, and changes in HDL composition and metabolism in COVID-19 (n = 48) and non-COVID pneumonia patients (n = 32). COVID-19 infection markedly reduced the activity of lecithin-cholesteryl-acyltransferase and functional parameters of HDL, such as the cholesterol efflux capacity, arylesterase activity of paraoxonase 1, and anti-oxidative capacity of apoB-depleted serum when compared to non-COVID pneumonia at baseline, paralleled by markedly reduced levels of HDL-cholesterol. Of particular interest, low HDL cholesterol efflux capacity was associated with increased mortality risk in COVID-19 patients, independent of HDL-C levels. Our results highlight profound effects of COVID-19 infection on HDL function, metabolism, and composition. Low HDL cholesterol efflux capacity indicates a fatal course of COVID-19, independent of HDL-cholesterol levels.

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“…These signaling cascades and some of these drivers have already been implicated with COVID-19, which attests to APNet’s overall capacity to make biologically plausible predictions. (Basile et al, 2022; Chidambaram et al, 2022; Merad and Martin, 2020; Pistollato et al, 2022; Thompson et al, 2021). A paradigmatic case concerning the translational value of APNet’s findings was the implication of MAPK pathway in severe COVID-19 based on various drivers (e.g., MAPK9, AREG, KIT, JUN, FLT3LG).…”

Section: Discussion - Conclusionmentioning

confidence: 99%

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19

Gavriilidis,

Vasileiou,

Dimitsaki

et al. 2024

Preprint

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MotivationComputational analyses of plasma proteomics provide translational insights into complex diseases such as COVID-19 by revealing molecules, cellular phenotypes, and signaling patterns that contribute to unfavorable clinical outcomes. Currentin silicoapproaches dovetail differential expression, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking.ResultsWe introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically-informed sparse deep learning model to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests co-expression and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19.Availability and ImplementationAPNet’s R, Python scripts and Cytoscape methodologies are available athttps://github.com/BiodataAnalysisGroup/APNetContactggeorav@certh.grSupplementary informationSupplementary information can be accessed in Zenodo (10.5281/zenodo.10438830).

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HDL cholesterol levels and susceptibility to COVID-19

Cited by 21 publications

References 45 publications

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns

The Significance of COVID-19 Diseases in Lipid Metabolism Pregnancy Women and Newborns

Low HDL Cholesterol Efflux Capacity Indicates a Fatal Course of COVID-19

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19

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