| Sažetak | Uvod: Koronavirusna bolest 2019. je visoko zarazna bolest uzrokovana SARS-CoV-2 virusom,
prvi put potvrđena u Wuhanu, Kini, 2019. godine. Njeno brzo širenje i katastrofalne globalne
posljedice na zdravlje i ekonomiju prisilile su cijelu zdravstvenu zajednicu na zajedničku borbu
za rješenjem. Biomarkeri moždane ozljede su objektivni indikatori kako bioloških i patoloških
procesa u organizmu te mogu biti korišteni u dijagnostičke, prevencijske i terapijske svrhe.
Ubikvitin karboksi-terminalna hidrolaza L1 je protein neurona koji se nalazi u citoplazmi.
Glijalni fibrilarni kiseli glikoprotein je strukturalni protein astrocita. Oba biomarkera su
istraživana u traumatskim ozljedama mozga, ali i kod netraumatskih patoloških procesa, kao
što su Parkinsonova i Alzheimerova bolest. Testosteron je primarni muški spolni hormon
odgovoran za regulaciju diferencijacije spola. Zbog češće pojavnosti COVID-19 kod
muškaraca, testosteron je uvelike istraživan u bolesnika s COVID-19. Glavni cilj ovog
istraživanja bio je istražiti dinamiku GFAP-a i UCH-L1 tijekom boravka bolesnika s teškom i
kritičnom COVID-19 u Jedinici intenzivnog liječenja. Nadalje, sekundarni ciljevi istraživanja
bili su istražiti jesu li razine GFAP i UCH-L1 više kod pacijenata koji su razvili neurološke
posljedice tijekom boravka u bolnici te istražiti jesu li razine testosterona povezane s GFAPom i UCH-L1.
Metode: Ova retrospektivna studija provedena je u Jedinici intenzivnog liječenja Klinike za
anesteziologiju, reanimatologiju i intenzivno liječenje Kliničkog bolničkog centra Split u
razdoblju od siječnja do svibnja 2022. godine. U studiju je uključeno 65 muških bolesnika u
dobi od 18 do 65 godina koji su liječeni u JIL-u zbog teške i kritične COVID-19 bolesti. Svi
uključeni pacijenti bili su intubirani i mehanički ventilirani pri prijemu u JIL. Po prijemu u JIL
bolesnicima je uzet uzorak krvi. Uzorci periferne venske krvi korišteni u ovoj studiji su izvađeni
prvi, sedmi i četrnaesti dan od prijema u JIL, osim u slučaju premještaja iz JIL-a ili smrtnog
ishoda bolesnika. Uzorci krvi su centrifugirani na 3000x g kroz 10 minuta te potom skladišteni
na -80°C do trenutka korištenja. Koncentracije GFAP i UCH-L1 su određivane iz seruma
koristeći kemiluminiscentnu imunokemijsku metodu (CMIA). Razine ukupnog testosterona su
određivane pomoći imunokemijske metode. Sve pretrage su napravljene po uputama
proizvođača.
Rezultati: Nije bilo značajne dinamike u serumskim koncentracijama biomarkera moždane
ozljede UCH-L1 i GFAP u razdoblju od dva tjedna boravka u JIL-u u muških bolesnika s teškim
i kritičnim oblikom COVID-19. Bolesnici s razvijenim neurološkim posljedicama imali su
značajnije duže vrijeme boravka u JIL-u i dulje su mehanički ventilirani (p = 0,014 i p = 0,010).
Razine testosterona pokazale su porast u bolesnika s teškim i kritičnim oblikom COVID-19
liječenih u JIL-u kroz tri točke mjerenja (p < 0,001). Prvi put je pokazana negativna korelacija
između UCH-L1 i serumskih razina testosterona (p < 0,001). Korelacija između GFAP i
testosterona nije utvrđena. Od bolesnika koji su preživjeli teški ili kritični oblik COVID-19,
bolesnici s razvijenim neurološkim posljedicama imaju značajno više razine UCH-L1 u serumu
(p = 0,022). Pronađena je značajna pozitivna korelacija između UCH-L1 i visokoosjetljivog
troponina (p = 0,007).
Zaključak: Nije utvrđena dinamika serumskih razina GFAP i UCH-L1 u bolesnika s teškim i
kritičnim oblikom COVID-19 liječenih u JIL-u, dok su razine testosterona pokazale porast u tri
točke mjerenja. Razine UCH-L1 bile su više pri prijemu u bolesnika s razvijenim neurološkim
posljedicama u odnosu na bolesnike bez, dok se razine GFAP pri prijemu nisu se razlikovale u
ispitivanim skupinama. Ovakav rezultat otvara mogućnost budućim ispitivanjima te
potencijalnim prognostičkim i terapijskim metodama. Razine UCH-L1 negativno su korelirale
s razinama testosterona u sve tri točke mjerenja, dok razine GFAP nisu pokazale korelaciju s
testosteronom. GFAP je imao pozitivnu korelaciju s dobi bolesnika. Razine UCH-L1, GFAP i
testosterona nisu se razlikovale u bolesnika koji su preživjeli i bolesnika koji su preminuli.
Pronađena je značajna pozitivna korelacija između UCH-L1 i visokoosjetljivog troponina. |
| Sažetak (engleski) | Background: Coronavirus disease 2019. is a highly contagious disease caused by the SARSCoV-2 virus, first confirmed in Wuhan, China, in 2019. Although it primarily affects the
respiratory system, it also causes damage to several other organ systems. Its rapid spread and
catastrophic global consequences on health and economy forced the entire health community
to fight together for a solution. Brain injury biomarkers are objective indicators of both
biological and pathological processes and thus can be used for diagnostic, preventive and
therapeutic purposes. Ubiquitin carboxy-terminal hydrolase L1 is a protein found in the
cytoplasm of neurons. Glial fibrillary acid protein is a structural protein of astrocytes. Both of
these biomarkers have been extensively investigated in traumatic brain injuries, but also in nontraumatic pathological processes, such as Parkinson's and Alzheimer's disease. Testosterone is
the primary male sex hormone responsible for regulating sex differentiation. Due to the more
frequent occurrence of COVID-19 in men, testosterone has been extensively investigated in
patients with COVID-19. The main goal of this study was to investigate the dynamics of GFAP
and UCH-L1 during the hospitalization of patients with severe and critical COVID-19 in the
Intensive Care Unit. Furthermore, secondary study objectives were to investigate whether
GFAP and UCH-L1 levels were higher in patients who developed neurological sequelae during
the hospital stay and to investigate whether testosterone levels were associated with GFAP and
UCH-L1.
Participants and methods: This retrospective study was conducted in the Intensive Care Unit
of the Department for Anesthesiology, Reanimatology and Intensive Care, University Hospital
of Split, Croatia in the period from January to May 2022. The study included 65 male patients
between the ages of 18 and 65 who were treated in the ICU for severe and critical form of
COVID-19. All included patients were intubated and mechanically ventilated upon admission
to the ICU. Exclusion criteria were: female sex, active malignant disease in the past year,
neuromuscular diseases, previous cerebrovascular incidents, autoimmune diseases, previously
diagnosed hypogonadism, heart failure, liver failure, and kidney failure. Upon admission to the
ICU blood samples were taken from the patients. Peripheral venous blood samples used in this
study were taken on the first, seventh and fourteenth day after admission to the ICU, except in
the case of transfer from the ICU or death of the patient. Blood samples were centrifuged at
3000x g for 10 minutes and then stored at -80°C. GFAP and UCH-L1 concentrations were determined from serum using a chemiluminescent immunochemical method (CMIA). Total
testosterone levels were determined using an immunochemical method. All tests were
performed according to the manufacturer's instructions.
Results: There were no significant differences in the serum concentrations of brain injury
biomarkers UCH-L1 and GFAP during a two-week stay in the ICU in male patients with severe
and critical form of COVID-19. Patients with developed neurological sequelae had longer ICU
stay and were mechanically ventilated for a longer period of time (p = 0.014 and p = 0.010). A
negative correlation between UCH-L1 and serum testosterone levels was demonstrated for the
first time (p < 0.001). A correlation between GFAP and testosterone has not been established.
Among patients who survived the severe or critical form of COVID-19, patients with developed
neurological sequelae have significantly higher levels of serum UCH-L1 (p = 0.022). A
significant positive correlation was found between UCH-L1 and high-sensitivity troponin (p =
0.007).
Conclusions: There was no significant difference in serum levels of GFAP and UCH-L1 in
patients with severe and critical form of COVID-19 treated in the ICU for two weeks, while
testosterone levels showed increase. UCH-L1 levels were higher at the admission in patients
with developed neurological sequelae compared to patients without, however, GFAP levels at
the admission did not differ between investigated groups. Also, UCH-L1 levels were negatively
correlated with testosterone levels at all three measurement points, while GFAP levels did not
show a correlation with testosterone. GFAP had a positive correlation with the age. The levels
of UCH-L1, GFAP and testosterone did not differ between patients who survived and patients
who died. A significant positive correlation was found between UCH-L1 and high-sensitivity
troponin. |
