ArticleVirology journal2025
Elucidating SARS-CoV-2 neurotropism: a comprehensive Mendelian randomization study on cerebrospinal fluid biomarkers and their relevance to COVID-19 neurological manifestations.
Article in Virology journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Neurological Manifestations of SARS-CoV-2.Viruses · 2025Pooled it
- Post-booster longitudinal plasma proteomic changes following BNT162b2 COVID-19 vaccination in Qatar.Frontiers in immunology · 2026Article
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Authors and funding
13 authors.
Funding
Abstract
A mendelian randomization (MR) analysis was conducted to investigate whether SARS-CoV-2 invaded the human nervous system. This was confirmed by an increase in biomarkers found in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients. To confirm the neuroinvasive properties of SARS-CoV-2, a series of analyses were conducted utilizing accessible datasets by MR. In addition, external validation was conducted by testing specific proteins in a retrospective cohort study, which included 40 COVID-19 patients with neurological complications and 15 disease controls (DC). Our investigation revealed the hospitalization, severity of COVID-19 increased the area and volume of certain brain regions, but no other significant causal effects were found of brain imaging-derived phenotypes (IDPs) on COVID-19. Notably, the COVID-19 hospitalization significantly increased the area and volume of the left caudal middle frontal gyrus (p_fdr = 0.012; p_fdr = 0.012, respectively). Additionally, COVID-19 severity was linked to the area, volume of the right caudal anterior-cingulate cortex and the volume of the right cuneus cortex (p_fdr = 0.023; p_fdr = 0.025; p_fdr = 0.026, respectively). In the CSF of COVID-19 patients, the median level of CHI3L1 was significantly higher (13677 pg/mL) compared to the DC group (8421 pg/mL, p < 1.00E-04). Similar trends were also found in CSF KLK6 and NGF-β. Additionally, the median NRGN level in plasma was significantly higher in the COVID-19 group (1013.00 pg/mL) compared to the control group (360.00 pg/mL, p = 6.50E-03). A subgroup analysis demonstrated that COVID-19 patients experiencing moderate to critical symptoms exhibited higher levels of GFAP in their CSF compared to those without. Elevated CSF levels of GFAP and S100B were also found in COVID-19 patients with decreased consciousness and comorbidities. This MR analysis provided evidence that SARS-CoV-2 may invade the human nervous system, as indicated by the increased levels of CSF biomarkers CHI3L1, NGF-β, and KLK6 in COVID-19 patients. These findings suggested that neuroinflammation could be a potential mechanism underlying the neurological complications seen in COVID-19 patients.
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