Evidence mapPaperPMID 40296111Full record

ArticleVirology journal2025

Elucidating SARS-CoV-2 neurotropism: a comprehensive Mendelian randomization study on cerebrospinal fluid biomarkers and their relevance to COVID-19 neurological manifestations.

Ziyan Wu, Honglin Xu, Siyuan Fan, Futai Feng, Zhan Li, Linlin Cheng, Haolong Li, Yongmei Liu, Haoting Zhan, Xinxin Feng and 3 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Ziyan Wu *Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Honglin Xu *Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Siyuan Fan *Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Futai FengDepartment of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.
Zhan LiDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Linlin ChengDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Haolong LiDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Yongmei LiuDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Haoting ZhanDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Xinxin FengDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Siyu WangDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China.
Shulan ZhangDepartment of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China. shulanpumch@126.com.
Yongzhe LiDepartment of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China. yongzhelipumch@126.com.

Funding

Beijing Natural Science Foundation M23008the CAMS Innovation Fund for Medical Sciences CIFMS: 2021-I2M-C&T-A-002the National High Level Hospital Clinical Research Funding 2022-PUMCH-B-124,2022-PUMCH-A-007the National Key Research and Development Program of China 2018YFE0207300the National Natural Science Foundation of China Grants 82472348
6 · The paper itself

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.

Indexed as

BiomarkersCOVID-19Nervous System DiseasesSARS-CoV-2AdultAgedBrainFemaleHumansMaleMendelian Randomization AnalysisMiddle AgedRetrospective StudiesSeverity of Illness IndexBiomarkersCOVID-19CSFMendelian randomizationNeuroinflammation.Neurological complications

Identifiers

PMID40296111
PMCPMC12036247

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.