Numerous neurological symptoms are associated with COVID-19, caused by SARS-CoV-2 infection, both in the acute phase of the disease and as long-term effects during post-acute sequelae of COVID-19. These include anosmia, dysgeusia, Guillain–Barré syndrome (GBS), stroke, encephalopathy, epilepsy, and neuropsychiatric symptoms [
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4]. Neurofilament light chain (NfL), as a constituent of the neuronal cytoskeleton, is a robust, well-known biomarker specific for neuroaxonal damage and has diagnostic and prognostic value in various neurological disorders such as amyotrophic lateral sclerosis, frontotemporal dementia, multiple sclerosis, or stroke [
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9]. Neurofilament light chain has been detected in serum (sNfL) and cerebrospinal fluid with commercially available assays. There are numerous studies showing the correlation between neurofilament light chain levels in serum or cerebrospinal fluid and neuroaxonal damage. Recent studies suggest sNfL as a potential neurological biomarker in COVID-19 addressing the putative neuroaxonal damage in COVID-19, which has not been proven up to today [
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12]. In one study hospitalized COVID-19 patients were found to have elevated sNfL levels regardless of neurological manifestations [
13]. Another study demonstrated a correlation between sNfL levels and an unfavorable clinical outcome in COVID-19 patients [
10]. Studies comparing sNfL in acute respiratory distress syndrome (ARDS) patients due to COVID-19 and bacterial pneumonia found elevated sNfL levels in both groups, suggesting a mechanism of sNfL elevation independent of SARS-CoV-2 in patients with ARDS [
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12]. However, all of these studies did not consider factors influencing sNfL levels, such as renal dysfunction, hypoxia, or body mass index [
14]. The exact pathomechanisms leading to COVID-19 causing neurological symptoms are still speculative, but the consequences of critical illness and hypoxia, hypercoagulopathy, para- and post-infectious inflammation, as well as the possible direct viral nerve infection may play a role [
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19]. In a post-mortem study, myositis-like histopathology was found in COVID-19 patients, indirectly suggesting presumed retrograde neuroaxonal injury from muscle pathology, which is more prevalent in COVID-19 ICU patients than previously thought before [
20]. Serum NfL levels remain highly elevated for months after brain injury, and higher sNfL levels have been shown to correlate with cardiovascular disease and peripheral neuropathies [
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23]. In addition, sNfL levels are elevated in patients with subclinical ischemic events in the brain, as has been found in some COVID-19 patients [
7]. Serum NfL levels are significantly elevated in patients after brain hypoxia and have better prognostic value than other serum markers including neuron-specific enolase, S100, and tau [
24]. The latter results raise the question of whether hypoxia caused by COVID-19 pneumonia may affect sNfL levels.
This study aimed to (i) examine sNfL in hospitalized COVID-19 patients, differentiated by oxygen treatment and clinical outcome, and (ii) test the hypothesis of whether sNfL level correlate with renal dysfunction or oxygen treatment in COVID-19 as a potential confounder of sNfL levels.