Association between Brain Injury Markers and Testosterone in Critically-Ill COVID-19 Male Patients

Abstract

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18–65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4–366.4) vs. 146.4 (92.5–243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2–40.1) vs. 29.8 (21.8–39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = −0.452, p < 0.001; r = −0.430, p < 0.001 and r = −0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients.

High Levels of NfL, GFAP, TAU, and UCH-L1 as Potential Predictor Biomarkers of Severity and Lethality in Acute COVID-19

“…When it comes to UCH-L1, Tokic et al (2022) investigated severity biomarkers and testosterone in severe COVID-19 male patients, then suggested that UCH-L1 may be related to neurological deficits in such population, reinforcing that this may be a relevant prognostic biomarker of neurological manifestation of COVID-19 [ 39 ].…”

Recuperative herbal formula Jing Si maintains vasculature permeability balance, regulates inflammation and assuages concomitants of “Long-Covid”

“…This study provides evidence to support that JSHT not only displays the anti-inflammatory effects in LPS-induced inflammation, but also significantly inhibited the entry of COVID-19 into the host by reducing the expression of TMPRSS2 in acute lung injury. In addition to the respiratory infection, evidences show that SARS-CoV-2 can infect central nervous system [89] , [90] , [91] . Reports on 2D static and 3D microfluidic in vitro models suggests that SARS-CoV-2 S protein may alter BBB function and reduce their integrity [92] .…”

Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection

“…A study has shown that protein ubiquitination exacerbates disease severity in affected individuals, which may imply its involvement in the development of complications (Huang et al, 2022). Research posits that the deubiquitinase UCHL1 potentially participates in the neuropathological damage and ensuing complications that stem from SARS-CoV-2 infection and may also possess prognostic value (De Lorenzo et al, 2021;Tokic et al, 2022). The M protein inhibits B-cell lymphoma 2 ovarian killer (BOK) by ubiquitinating it.…”