Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients

Alhaji H. Janneh; Mohamed Faisal Kassir; Connor J. Dwyer; Paramita Chakraborty; Jason S. Pierce; Patrick A. Flume; Hong Li; Satish N. Nadig; Shikhar Mehrotra; Besim Ogretmen

doi:10.1038/s41598-021-93857-7

Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients

Alhaji H. Janneh, Mohamed Faisal Kassir, Connor J. Dwyer, Paramita Chakraborty, Jason S. Pierce, Patrick A. Flume, Hong Li, Satish N. Nadig, Shikhar Mehrotra, Besim Ogretmen^*

^*Corresponding author for this work

Surgery, Transplant Surgery Division

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus’s spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients’ serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.

Original language	English (US)
Article number	14232
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-93857-7
State	Published - Dec 2021

Funding

This work was supported in part by the Medical University of South Carolina\u2019s Lipidomics Shared Resource through the funding of laboratory space for the Analytical Unit located in 505 Children\u2019s Research Institute (CRI): Hollings Cancer Center (P30 CA138313), the Lipidomics Shared Resource in the South Carolina Lipidomics and Pathobiology COBRE (P30 GM103339); MUSC Department of Biochemistry (P20 RR017677), the National Center for Research Resources and Office of the Director of the National Institutes of Health (C06 RR018823)\u201D, Hollings Cancer Center Support Grant (P30 CA138313), and individual research grants (CA214641, DE016572, and P01 CA203628 to BO) from the National Institutes of Health.

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10.1038/s41598-021-93857-7

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title = "Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients",

abstract = "COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus{\textquoteright}s spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients{\textquoteright} serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.",

author = "Janneh, {Alhaji H.} and Kassir, {Mohamed Faisal} and Dwyer, {Connor J.} and Paramita Chakraborty and Pierce, {Jason S.} and Flume, {Patrick A.} and Hong Li and Nadig, {Satish N.} and Shikhar Mehrotra and Besim Ogretmen",

note = "Funding Information: This work was supported in part by the Medical University of South Carolina{\textquoteright}s Lipidomics Shared Resource through the funding of laboratory space for the Analytical Unit located in 505 Children{\textquoteright}s Research Institute (CRI): Hollings Cancer Center (P30 CA138313), the Lipidomics Shared Resource in the South Carolina Lipidomics and Pathobiology COBRE (P30 GM103339); MUSC Department of Biochemistry (P20 RR017677), the National Center for Research Resources and Office of the Director of the National Institutes of Health (C06 RR018823)”, Hollings Cancer Center Support Grant (P30 CA138313), and individual research grants (CA214641, DE016572, and P01 CA203628 to BO) from the National Institutes of Health. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s41598-021-93857-7",

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AU - Janneh, Alhaji H.

AU - Kassir, Mohamed Faisal

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AU - Chakraborty, Paramita

AU - Pierce, Jason S.

AU - Flume, Patrick A.

AU - Li, Hong

AU - Nadig, Satish N.

AU - Mehrotra, Shikhar

AU - Ogretmen, Besim

N1 - Funding Information: This work was supported in part by the Medical University of South Carolina’s Lipidomics Shared Resource through the funding of laboratory space for the Analytical Unit located in 505 Children’s Research Institute (CRI): Hollings Cancer Center (P30 CA138313), the Lipidomics Shared Resource in the South Carolina Lipidomics and Pathobiology COBRE (P30 GM103339); MUSC Department of Biochemistry (P20 RR017677), the National Center for Research Resources and Office of the Director of the National Institutes of Health (C06 RR018823)”, Hollings Cancer Center Support Grant (P30 CA138313), and individual research grants (CA214641, DE016572, and P01 CA203628 to BO) from the National Institutes of Health. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12

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N2 - COVID-19 pandemic exerts a health care emergency around the world. The illness severity is heterogeneous. It is mostly unknown why some individuals who are positive for SARS-CoV-2 antibodies stay asymptomatic while others show moderate to severe disease symptoms. Reliable biomarkers for early detection of the disease are urgently needed to attenuate the virus’s spread and help make early treatment decisions. Bioactive sphingolipids play a crucial role in the regulation of viral infections and pro-inflammatory responses involved in the severity of COVID-19. However, any roles of sphingolipids in COVID-19 development or detection remain unknown. In this study, lipidomics measurement of serum sphingolipids demonstrated that reduced sphingosine levels are highly associated with the development of symptomatic COVID-19 in the majority (99.24%) SARS-CoV-2-infected patients compared to asymptomatic counterparts. The majority of asymptomatic individuals (73%) exhibited increased acid ceramidase (AC) in their serum, measured by Western blotting, consistent with elevated sphingosine levels compared to SARS-CoV-2 antibody negative controls. AC protein was also reduced in almost all of the symptomatic patients’ serum, linked to reduced sphingosine levels, measured in longitudinal acute or convalescent COVID-19 samples. Thus, reduced sphingosine levels provide a sensitive and selective serologic biomarker for the early identification of asymptomatic versus symptomatic COVID-19 patients.

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Alterations of lipid metabolism provide serologic biomarkers for the detection of asymptomatic versus symptomatic COVID-19 patients

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