Biomarkers in relation to outcome after severe traumatic brain injury and severe covid-19

Abstract

Intro: A severe traumatic brain injury (sTBI) causes neuronal and astrocytic injuries, initiating a cascade of mechanisms further exacerbating the damage. Similarly, a severe covid-19 infection can cause brain damage by the virus itself or via hypoxia or inflammation. Aims: This thesis explores brain injury related short- and long-term outcomes after a sTBI or a severe covid-19. Further, it investigates how proteins specific to neurons and astrocytes, and a genetic marker, relate to these outcomes. Method: Paper I-III: sTBI-patients were assessed by Glasgow outcome scale (GOS) one-year and 10-15 years after trauma. Mortality was compared with a matched Swedish population (Paper I). Cerebrospinal fluid (CSF) and blood was collected during initial 3 weeks and one-year after trauma (only blood). Paper IV: Severe covid-19 survivors gave blood samples and were assessed according to Montreal Cognitive assessment 4-6 months after ICU-discharge. A subset of patients also had blood samples collected at admission. Neurofilament light (NfL) and Glial fibrillary acidic protein (GFAP) in CSF, was analyzed with enzyme-linked immunosorbent assay (paper II). Total-tau in serum (paper III) and NfL, GFAP, total-tau, pTau181 and pTau231 in plasma (paper IV) was analyzed with single molecular array. APOE-polymorphism was analyzed with polymerase chain reaction. Results: We showed that approximately 50% of patients after a sTBI suffer long-term unfavorable outcome, including a higher mortality rate than a matched Swedish population (paper I). Higher concentrations of NfL and GFAP in CSF the first two weeks after trauma (paper II) and higher concentrations of total-tau in serum on days 3-12 were associated with worse one-year and 10-15 years outcome. APOE 4-carriers had higher total-tau concentrations 10-12 days after trauma than non-carriers (paper III). Finally, almost 50% of severe covid-19 survivors had cognitive impairment 4-6 months after ICU-discharge, mostly influenced by age (Paper IV). Conclusion: Many survivors have lingering symptoms related to brain insult after a sTBI or a severe covid-19 infection and biomarkers might give an early indication of prognosis. However, other relevant factors such as age need to be considered.