Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19

Abstract Objective Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVI...

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Autores principales:	Jude Savarraj, Eun S. Park, Gabriela D. Colpo, Sarah N. Hinds, Diego Morales, Hilda Ahnstedt, Atzhiry S. Paz, Andres Assing, Fudong Liu, Shivanki Juneja, Eunhee Kim, Sung-min Cho, Aaron M. Gusdon, Pramod Dash, Louise D. McCullough, H. Alex Choi
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Brain injury COVID-19 SARS-CoV-2 Inflammation Endothelial injury Sex differences Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a2e653b59277428d8e2e0f5a7aef6ae4
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spelling	oai:doaj.org-article:a2e653b59277428d8e2e0f5a7aef6ae42021-11-28T12:37:37ZBrain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-1910.1186/s12974-021-02323-81742-2094https://doaj.org/article/a2e653b59277428d8e2e0f5a7aef6ae42021-11-01T00:00:00Zhttps://doi.org/10.1186/s12974-021-02323-8https://doaj.org/toc/1742-2094Abstract Objective Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes. Methods Plasma samples from 57 subjects at < 48 h of COVID-19 hospitalization, and 20 matched controls were interrogated for the levels of six BIMs—including GFAP, S100B, Syndecan-1, UCHLI, MAP2 and NSE, two EIMs—including sICAM1 and sVCAM1. Additionally, several cytokines/chemokines were analyzed by multiplex. Statistical and bioinformatics methods were used to measure differences in the marker profiles across (a) COVID-19 vs. controls and (b) men vs. women. Results Three BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (p < 0.05) elevated in the COVID-19 cohort compared to controls. Bioinformatics analysis reveal a stronger positive association between BIM/CC/EIMs in the COVID-19 cohort. Analysis across sex revealed that several BIMs and CCs including NSE, IL10, IL15 and IL8 were significantly (p < 0.05) higher in men compared to women. Men also expressed a more robust BIM/ EIM/CC association profile compared to women. Conclusion The acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization are suggestive of brain and endothelial injury. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.Jude SavarrajEun S. ParkGabriela D. ColpoSarah N. HindsDiego MoralesHilda AhnstedtAtzhiry S. PazAndres AssingFudong LiuShivanki JunejaEunhee KimSung-min ChoAaron M. GusdonPramod DashLouise D. McCulloughH. Alex ChoiBMCarticleBrain injuryCOVID-19SARS-CoV-2InflammationEndothelial injurySex differencesNeurology. Diseases of the nervous systemRC346-429ENJournal of Neuroinflammation, Vol 18, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Brain injury COVID-19 SARS-CoV-2 Inflammation Endothelial injury Sex differences Neurology. Diseases of the nervous system RC346-429
spellingShingle	Brain injury COVID-19 SARS-CoV-2 Inflammation Endothelial injury Sex differences Neurology. Diseases of the nervous system RC346-429 Jude Savarraj Eun S. Park Gabriela D. Colpo Sarah N. Hinds Diego Morales Hilda Ahnstedt Atzhiry S. Paz Andres Assing Fudong Liu Shivanki Juneja Eunhee Kim Sung-min Cho Aaron M. Gusdon Pramod Dash Louise D. McCullough H. Alex Choi Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
description	Abstract Objective Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes. Methods Plasma samples from 57 subjects at < 48 h of COVID-19 hospitalization, and 20 matched controls were interrogated for the levels of six BIMs—including GFAP, S100B, Syndecan-1, UCHLI, MAP2 and NSE, two EIMs—including sICAM1 and sVCAM1. Additionally, several cytokines/chemokines were analyzed by multiplex. Statistical and bioinformatics methods were used to measure differences in the marker profiles across (a) COVID-19 vs. controls and (b) men vs. women. Results Three BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (p < 0.05) elevated in the COVID-19 cohort compared to controls. Bioinformatics analysis reveal a stronger positive association between BIM/CC/EIMs in the COVID-19 cohort. Analysis across sex revealed that several BIMs and CCs including NSE, IL10, IL15 and IL8 were significantly (p < 0.05) higher in men compared to women. Men also expressed a more robust BIM/ EIM/CC association profile compared to women. Conclusion The acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization are suggestive of brain and endothelial injury. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.
format	article
author	Jude Savarraj Eun S. Park Gabriela D. Colpo Sarah N. Hinds Diego Morales Hilda Ahnstedt Atzhiry S. Paz Andres Assing Fudong Liu Shivanki Juneja Eunhee Kim Sung-min Cho Aaron M. Gusdon Pramod Dash Louise D. McCullough H. Alex Choi
author_facet	Jude Savarraj Eun S. Park Gabriela D. Colpo Sarah N. Hinds Diego Morales Hilda Ahnstedt Atzhiry S. Paz Andres Assing Fudong Liu Shivanki Juneja Eunhee Kim Sung-min Cho Aaron M. Gusdon Pramod Dash Louise D. McCullough H. Alex Choi
author_sort	Jude Savarraj
title	Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
title_short	Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
title_full	Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
title_fullStr	Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
title_full_unstemmed	Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19
title_sort	brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after covid-19
publisher	BMC
publishDate	2021
url	https://doaj.org/article/a2e653b59277428d8e2e0f5a7aef6ae4
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Brain injury, endothelial injury and inflammatory markers are elevated and express sex-specific alterations after COVID-19

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