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

Journal of Neuroinflammation

Jude Savarraj¹  H. Alex Choi¹  Andres Assing¹  Eunhee Kim¹  Sarah N. Hinds¹  Aaron M. Gusdon¹  Atzhiry S. Paz¹  Eun S. Park¹  Pramod Dash²  Diego Morales³  Hilda Ahnstedt³  Louise D. McCullough³  Gabriela D. Colpo³  Shivanki Juneja³  Fudong Liu³  Sung-min Cho⁴ 

[1] Departent of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, 6431 Fannin St, 77030, Houston, TX, USA;Department of Neurobiology, McGovern Medical School, The University of Texas Health Science Center at Houston, 77030, Houston, TX, USA;Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, 77030, Houston, TX, USA;Johns Hopkins University School of Medicine, 21205, Baltimore, MD, USA;

关键词: Brain injury;    COVID-19;    SARS-CoV-2;    Inflammation;    Endothelial injury;    Sex differences;   

DOI  :  10.1186/s12974-021-02323-8

来源: Springer

【 摘 要 】

ObjectiveAlthough 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.MethodsPlasma 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.ResultsThree 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.ConclusionThe 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.

【 授权许可】

CC BY