TABLE 1.
Summary of circulating biomarkers associated with neurological dysfunction showing potential dysregulation in COVID-19.
| Biomarker | Source | Function | Pathophysiology | Status in neurodegenerative diseases | Patients’ information | Status in COVID-19 |
References |
| GFAP | Serum/ plasma |
Provides stability to astrocytes influencing their shape and movement. | Astrocytes damage and inflammation | AD- increased PD- increased MS- increased |
1. 47 COVID-19 patients divided into 3 groups related to systemic disease severity. 2. 100 COVID-19 patients classified into three main groups: mild, moderate and severe patients. 3. 58 COVID-19 patients divided into 3 groups related to disease severity. 4. 251 hospitalized COVID-19 patients aged between 60-83 years without a history of dementia |
Significantly increased | Eng et al., 2000; Elahi et al., 2020; Kanberg et al., 2020, 2021; Frontera et al., 2022; Heimfarth et al., 2022; Kim et al., 2022; Sahin et al., 2022 |
| NFL | Serum/ plasma |
Provide cytoskeletal stability and allow for radial growth of neurons. | Neuroaxonal injury | AD- increased PD- increased ALS- increased HD- increased LBD- increased |
1. 104 COVID-19 patients 2. COVID-19 Patients classified into 3 groups according to the disease severity: mild (n = 24), moderate (n = 28), and severe (n = 48). 3. 142 hospitalized COVID-19 4. 251 hospitalized COVID-19 patients aged between 60-83 years without a history of dementia 5. 57 hospitalized Covid-19 patients without major neurological manifestations |
Significantly increased | Yuan et al., 2017; Gaetani et al., 2019; Palermo et al., 2020; Rajan et al., 2020; De Lorenzo et al., 2021; Kanberg et al., 2021; Prudencio et al., 2021; Verde et al., 2021, 2022; Chouliaras et al., 2022; Frontera et al., 2022; Thijssen et al., 2022; Zanella et al., 2022 |
| P-tau 181 | Serum/ plasma |
Maintaining neuronal microtubule integrity by providing stability and encouraging assembly. | Form neurofibrillary tangles | AD- increased | 1. 16 COVID-19 volunteers without neurological symptoms and 8 COVID-19 volunteers with neurological symptoms 2. 251 hospitalized COVID-19 patients aged between 60-83 years without a history of dementia |
Significantly increased | Metaxas and Kempf, 2016; Wang and Mandelkow, 2016; Moscoso et al., 2021; Sun et al., 2021; Frontera et al., 2022; Smirnov et al., 2022 |
| UCH-L1 | Plasma | Removing ubiquitin from their target proteins maintaining the nervous system integrity. | Changes in regulating the function of various synapses influencing their maintenance, transmission, and plasticity. | PD- increased AD-increased FA- increased |
1. 27 hospitalized COVID-19 patients aged 54-76 years without major neurological manifestations 2. 251 hospitalized COVID-19 patients aged between 60-83 years without a history of dementia 3. 104 COVID-19 patients aged 49- 67 |
Significantly increased |
Bishop et al., 2016; Zeitlberger et al., 2018; Cooper et al., 2020; Ng et al., 2020; De Lorenzo et al., 2021; Bogdan et al., 2022; Frontera et al., 2022 |
| S100B | Serum | Regulation of cell proliferation and cytoskeletal structure | Cause astrocyte damage and injury | AD- increased PD- increased ALS- increased MS- increased |
1. 74 hospitalized COVID-19 patients 2. 64 COVID-19 patients (34 mild cases; 30 severe cases) 3. 57 patients hospitalized with COVID-19 4. 58 COVID-19 Patients classified into mild (n = 17), moderate (n = 18), and severe (n = 23). |
Significantly increased | Steiner et al., 2007; Lam et al., 2013; Barateiro et al., 2016; Serrano et al., 2017; Cristovao and Gomes, 2019; Aceti et al., 2020; Angelopoulou et al., 2021; Mete et al., 2021; Savarraj et al., 2021; Sahin et al., 2022 |
| NSE | Serum/ plasma |
Regulating neuronal growth, differentiation, survival. | Cause axonal injury and neuroinflammation | AD-increased HD-increased BPAN-increased |
1. 252 COVID-19 patients classified into 3 groups according to the disease severity. 2. 128 hospitalized COVID-19 patients 3. 57 COVID-19 hospitalized patients |
Significantly increased | Chaves et al., 2010; Ciancarelli et al., 2014; Polcyn et al., 2017; Takano et al., 2017; Haque et al., 2018; Wei et al., 2020; Cione et al., 2021; Savarraj et al., 2021 |
| Inflammatory cytokines | Serum | Mobilization of immune cells | Cytokine storm implicated in neurotoxicity, disruption of the integrity of BBB, neuroglial cells activation, and neuroinflammation | AD-increased | 1. 57 COVID-19 hospitalized patients 2. 43 COVID-19 patients with mild-moderate (n = 39) and severe (n = 14) 3. 33 COVID-19 patients 4. 60 COVID-19 patients divided in to two subgroup, clinical group (n = 32), participants seeking care for post-acute cognitive complaints and a non-clinical group (n = 28), participants patients who did not seek care for post-acute COVID-19. |
Significantly increased | Gupta et al., 2020b; Xin et al., 2021; Acosta-Ampudia et al., 2022; Ferrando et al., 2022; Hirzel et al., 2022; Lu et al., 2022; Schultheiss et al., 2022; Zhang et al., 2022b |
Ischemia stroke (IS), Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), Multiple system atrophy (MSA), mild cognitive impairment (MIC), Huntington’s Disease (HD), Lewy body dementia (LBD), Friedreich’s Ataxia (FA), beta-propeller protein-associated neurodegeneration (BPAN).