Impact of COVID-19 on central nervous system biomarkers: A comparative analysis

Introduction

In late 2019, SARS-CoV-2 emerged in Wuhan, China,leading to a worldwide pandemic. By February 2020,Najaf in Iraq reported its initial COVID-19 cases. Twoweeks later, Iraq's Ministry of Health confirmed 101positive cases and nine deaths across fourteenprovinces, with nearly 40% in Baghdad (Al-Sarrayand Shareef, 2022)

SARS-CoV-2 can cause a cytokine storm, leading toinflammation that compromises the blood-brainbarrier. This may result in brain tissue damage andvarious neurological complications, although suchsevere outcomes are more common in serious cases ofCOVID-19 (Thepmankorn et al., 2021). A cytokinestorm is characterized by an excessive production ofpro-inflammatory cytokines, including interleukin(IL)-6, IL-2, IL-7, and tumor necrosis factor (TNF)-α.Recent research has indicated that COVID-19 patientsin intensive care units exhibit increased levels of IL24 in their bloodstream (Nazzal and Sabbar, 2022).

In addition to post-recovery effects like "brain fog"severe COVID-19 case frequently result in cognitivedisorders like confusion, delirium, and a low level ofconsciousness (Otani et al., 2023). The virus alsoresults in long-lasting neurological problems such asjoint, chest pain, anosmia, and ageusia (Sarıoğlu etal., 2023). COVID-19's respiratory side effects anddamage might cause problems such brain hypoxia,which may result in long-term cognitive and physicaldeficits (Dondaine et al., 2022). Furthermore, there isa notable influence on mental health, as seen by thehigh prevalence of anxiety, depression, and stressfollowing recovery (Iqbal et al., 2021). Additionally,there is a symptom overlap between myalgicencephalomyelitis /chronic fatigue syndrome(ME/CFS) and long-term COVID-19 effects(Sokocheva et al., 2022). The virus disproportionatelyaffects particular racial and ethnic populations andincreases the risk for people with underlying diseasessuch diabetes, obesity, and cerebrovascular illness(Carethers, 2021).

According to recent studies, direct viral entry andinflammatory reactions are the ways that COVID-19may affect the central nervous system (Spudich andNath, 2022). According to studies, the virus mayenter the central nervous system CNS through theblood-brain barrier or the olfactory bulb, which couldexplain a variety of neurological symptoms thatpatients experience. Acute cerebrovascular episodes,encephalitis, headaches, and anosmia are amongthese symptoms (Khatoon et al., 2022). Additionallylinked to CNS involvement and possibly causingneurological impairment in COVID-19 patients areinflammatory responses such cytokine storms (Salekiet al., 2021). The increasing amount of data highlightsthe necessity for additional study to completelycomprehend the neurological effects of COVID-19. 

Important biomarkers for determining brain damageand neurological involvement include neurofilamentlight (NFL), tau, glial fibrillary acidic protein (GFAP),and neuron-specific enollase (NSE). Because NSEmeasures impairment to neuronal function directly, itis useful for assessing traumatic brain injury (TBI)(Mendoza et al., 2020). Tau and GFAP are brainspecific protein biomarkers that have been thoroughlyinvestigated in traumatic brain injury (TBI) and offerinsights into neuronal and astrocyte damage (Dadaset al., 2018; Nishimura et al., 2022). Furthermore,blood tests for GFAP and NFL, a marker of axonalingury, provide a straightforward way to diagnose andprognostic TBI, especially in mild instances (Zhang etal., 2016). These biomarkers are critical for correctneurological condition assessment andmanagement, as they play a major role in knowingthe pathophysiological state of brain damage(Wang et al., 2018; Kulbe and Geddes, 2015; Wildeet al., 2023).

When evaluating brain damage and cognitiveinvolvement in COVID-19 patients, neurofilamentlight (NFL) glial fibrillary acidic protein (GFAP), tau,and neuron-specific enolase (NSE) are essentialmarkers. Study has demonstrated that thesebiomarkers, which indicate brain damage andendothelial injury with sex-specific changes, areincreased in COVID-19 individuals exhibitingneurological symptoms (Sahin et al., 2022; Needhamet al., 2022). These biomarkers can also clarify neuroaxonal and astrogliail injuries, offering informationabout the pathophysiological condition of brain damage in COVID-19 affected individuals (Telser etal., 2023). The importance of these biomarkers indetermining brain injury in COVID-19 patients ishighlighted by the correlation between elevated levelsof these markers and poor outcomes and the severityof condition (Dekosky et al., 2020; Silva et al., 2023). 

These central nervous system(CNS) experiencesdemyelination and neurodegeneration in multiplesclerosis(MS) , a chronic inflammatory illness thatcauses a variety of neurological symptoms. Threefactors contribute to the pathophysiology of MS:autoimmune, neurodegeneration, and CNSinflammation (Richter et al., 2021). Encephalitis,acute cerebrovascular, and other central nervoussystem signs have been linked to COVID-19, a virusgenerated by the SARS-CoV-2 virus (Maury et al.,2021). Both MS and COVID-19 can lead toneurological involvement, making MS a comparativemodel in studying COVID-19-related neurologicalissues (Schwartz et al., 2022).

Similarities between the pathophysiology of MS andCOVID-19-related neurological issues include theinvolvement of inflammatory processes in CNSdamage. Both conditions can lead toneuroinflammation and neurodegeneration,contributing to neurological symptoms (Conway etal., 2022). However, differences exist in theunderlying mechanisms, with MS being anautoimmune disease affecting the CNS, while COVID19 primarily involves viral infection and systemicinflammatory responses (Fernandes de Souza et al.,2023). It was shown that individuals with MS mayhave worse COVID-19 outcomes compared to thegeneral population, indicating a potential interactionbetween MS and COVID-19 (Barzegar et al., 2023).The impact of COVID-19 on people with MS has beena subject of research, with some studies reporting anincreased risk of hospitalization and mortality in MSpatients (Sormani et al., 2022). However, otherstudies have suggested that MS may not be associatedwith an increased risk for severe COVID-19 (MorenoTorres et al., 2021).

Biomarkers play a crucial role in the diagnosis,prognosis, and management of multiple sclerosis(MS). Neurofilament light (NFL), glial fibrillary acidicprotein (GFAP), tau, and neuron-specific enolase(NSE) are some of the biomarkers that have beenstudied in MS. NFL, a marker of axonal injury, iselevated in MS patients, indicating neuroaxonaldamage (Arneth and Kraus, 2022). Two brain-specificprotein biomarkers that shed light on MS-relatedastroglial injury and neuronal impairment are tau andGFAP (Momtazmanesh et al., 2020). NSE is useful inevaluating (MS) since it is a measure of impairmentto neuronal function (Gyang and Rempe, 2021). Theidentification of MS, assessment of disease activity,and evaluation of therapy response can all be aided bythese biomarkers (Serafeim and Anagnostouli, 2013).Furthermore, biomarkers can help distinguishbetween different MS subtypes, predict relapses, andsuggest tailored treatment plans (Buck and Hemmer,2014). In order to improve patient outcomes by earlyidentification and efficient treatment of the disease,biomarkers must be used in MS management.(Arneth and Kraus, 2022). 

This research fills a major knowledge gap about theeffects of COVID-19 on the central nervous system(CNS) and draws comparisons with multiple sclerosis,with a focus on the particulars of Erbil City, KRG,Iraq. Comprehending these associations is essentialfor formulating focused treatments and handlingtactics. The findings could offer important insightsinto the neurological manifestations of the virus andMultiple Sclerosis in other populations, perhapsdirecting global health responses, given the numerousethnic and environmental conditions in Erbil City.

Investigating the effect of COVID-19 on centralnervous system biomarkers and comparing it with theeffects seen in MS patients and healthy controls is themain goal of this study. Our goal is to investigate theidea that, in contrast to what is seen in multiplesclerosis, COVID-19 induces notable changes inseveral biomarkers (NFL, GFAP, tau, and NSE) linkedto brain injury. This research seeks to bridge thegap in understanding the neurological implicationsof COVID-19 in comparison to a well-characterizedneurological disorder like MS, thereby contributingto the broader knowledge of virus-inducedneurological damage.