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

• Published in: Journal of neuroinflammation Vol. 18; no. 1; p. 277
• Main Authors: Savarraj, Jude, Park, Eun S, Colpo, Gabriela D, Hinds, Sarah N, Morales, Diego, Ahnstedt, Hilda, Paz, Atzhiry S, Assing, Andres, Liu, Fudong, Juneja, Shivanki, Kim, Eunhee, Cho, Sung-Min, Gusdon, Aaron M, Dash, Pramod, McCullough, Louise D, Choi, H Alex
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27.11.2021; BioMed Central; BMC
• Subjects: Adult; Aged; Bioinformatics; Biological markers; Biomarkers - blood; Brain; Brain Injuries - blood; Brain Injuries - complications; Brain Injuries - pathology; Brain injury; Cardiovascular disease; Chemokines; Coronaviruses; COVID-19; COVID-19 - complications; Cytokines - blood; Demographic aspects; Diabetes; Disability; Endothelial injury; Endothelium; Endothelium - pathology; Female; Gender differences; Glial fibrillary acidic protein; Health aspects; Hospitalization; Humans; Hypertension; Immune response; Inflammation; Inflammation - blood; Inflammation - complications; Inflammation - pathology; Injuries; Interleukin 1; Interleukin 1 receptor antagonist; Interleukin 10; Interleukin 15; Interleukin 8; Male; Middle Aged; Mortality; Patients; Plasma; Proteins; Respiratory diseases; Risk factors; S100b protein; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Sex Characteristics; Sex differences; Sex Factors; Syndecan; Traumatic brain injury; Tumor necrosis factor-α; Variables; United States; United States > US; Texas; COVID-19; Sex differences; SARS-CoV-2; Inflammation; Endothelial injury; Brain injury
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-021-02323-8

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. 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. 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. 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.