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

J Neuroinflammation. 2021 Nov 27;18(1):277. doi: 10.1186/s12974-021-02323-8.

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.

Keywords: Brain injury; COVID-19; Endothelial injury; Inflammation; SARS-CoV-2; Sex differences.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Brain Injuries / blood
  • Brain Injuries / complications*
  • Brain Injuries / pathology*
  • COVID-19 / complications*
  • Cytokines / blood*
  • Endothelium / pathology*
  • Female
  • Hospitalization
  • Humans
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation / pathology*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • Sex Characteristics
  • Sex Factors

Substances

  • Biomarkers
  • Cytokines