Evidence map›Paper›PMID 39709771›Full record

ArticleEBioMedicine2025

Combination of spatial transcriptomics analysis and retrospective study reveals liver infection of SARS-COV-2 is associated with clinical outcomes of COVID-19.

Shiqi Chen, Yi Zhang, Asha Ashuo, Shu Song, Lunzhi Yuan, Weixia Wang, Cong Wang, Zunguo Du, Yangtao Wu, Dan Tan and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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

7 citing papers in PubMed.

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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

22 authors.

Shiqi ChenDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Yi ZhangShanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China.
Asha AshuoKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Shu SongShanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China.
Lunzhi YuanState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Weixia WangQingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Cong WangShanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, Shanghai, China.
Zunguo DuDepartment of Pathology, Huashan Hospital, Fudan University, Shanghai, China.
Yangtao WuState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Dan TanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Chenlu HuangLiver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Jingna ChenKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Yaming LiKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Jinjin BaiLiver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China.
Huilin GuoState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Zehong HuangState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Yi GuanState Key Laboratory of Emerging Infectious Diseases, University of Hong Kong, Hong Kong, China; Joint Institute of Virology (Shantou University and University of Hong Kong), Guangdong-Hongkong Joint Laboratory of Emerging Infectious Diseases, Shantou University, Shantou, China.
Ningshao XiaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China. Electronic address: nsxia@xmu.edu.cn.
Zhenghong YuanKey Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhyuan@shmu.edu.cn.
Jiming ZhangDepartment of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: jmzhang@fudan.edu.cn.
Quan YuanState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China. Electronic address: yuanquan@xmu.edu.cn.
Zhong FangLiver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China. Electronic address: zhongfang13@fudan.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLiver involvement is a common complication of coronavirus disease 2019 (COVID-19), especially in hospitalized patients. However, the underlying mechanisms involved are not fully understood.

methodsImmunohistochemistry (IHC) staining of SARS-CoV-2 spike (S) and nucleocapsid (N) proteins was conducted on liver tissues from six patients with COVID-19. The 10x Genomics Visium CytAssist Spatial Gene Assay was designed to analyze liver transcriptomics. TCR CDR3 sequences were analyzed in DNA from liver tissues. Liver function indicators were retrospectively studied in 650 hospitalized patients with COVID-19.

findingsSARS-CoV-2 proteins were initially detected in the livers of naturally infected golden (Syrian) hamsters, prompting us to investigate the situation in clinical cases. Thus, we collected liver tissues from patients with abnormal liver biochemical values. Viral S and N proteins were detected in the livers of severe and deceased patients but not in those of moderate patients. We further demonstrated that hepatocytes and erythroid cells in hepatic sinusoids are major cells targeted by SARS-CoV-2. Immune cells, especially T cells, were enriched in surviving severe patients, characterized by enhanced CDR3α clonality and novel CDR3β recombination of the T-cell receptor. In contrast, hepatocyte apoptosis was triggered, and the transcription of albumin (ALB) was obviously impaired in the deceased patients. We then performed a retrospective study including patients with COVID-19. Serum aspartate aminotransferase (AST) and ALB levels at baseline significantly differed in the deceased cohort. However, AST regression did not decrease the risk of death. ALB recovery indicated clinical improvement, and declining or low serum ALB concentrations were associated with death.

interpretationThis study provides clinical evidence for liver infection with SARS-CoV-2, insight into the impact of SARS-CoV-2 on the liver, and a potential way to evaluate the risk of death via assessing serum ALB concentration fluctuations in patients with COVID-19.

fundingNational Key R&D Program of China (2021YFC2300602), National Natural Science Foundation of China (92369110), National Natural Science Foundation of China (U23A20474), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), Shanghai Jinshan District Medical and Health Technology Innovation Fund Project (2023-WS-31).

Indexed as

COVID-19LiverSARS-CoV-2AdultAgedAnimalsCoronavirus Nucleocapsid ProteinsFemaleGene Expression ProfilingHumansLiver DiseasesMaleMiddle AgedPhosphoproteinsRetrospective StudiesSpike Glycoprotein, CoronavirusCoronavirus Nucleocapsid Proteinsnucleocapsid phosphoprotein, SARS-CoV-2PhosphoproteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2ALBCOVID-19LiverSARS-COV-2Spatial transcriptome

Identifiers

PMID39709771
PMCPMC11732063

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LicenceCC BY-NC-ND
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Registered trials

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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 OpenQuestion graph.