ArticleFrontiers in immunology2021
Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Prenatal social support in low-risk pregnancy shapes placental epigenome.BMC medicine · 2023Trial
- Mechanistic study of MUC3A in promoting progression of clear cell renal cell carcinoma via the JAK‑STAT pathway.Oncology reports · 2026Article
- Association between coronavirus disease 2019 and new-onset autoimmune diseases during the early phase of the pandemic.PloS one · 2026Article
- Host-Strain-Specific Responses to Pneumonia Virus of Mice Infection: A Study of Lesions, Viral Load, and Cytokine Expression.Viruses · 2025Article
- LILRA5Frontiers in cellular and infection microbiology · 2025Article
- Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease.CNS neuroscience & therapeutics · 2024Article
- Review
- Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Can Waves of Autoimmune Diseases Occur after the COVID-19 Pandemic?Infectious disorders drug targets · 2024Article
- Network-based integrative multi-omics approach reveals biosignatures specific to COVID-19 disease phases.Frontiers in molecular biosciences · 2024Article
- High risk of autoimmune diseases after COVID-19.Nature reviews. Rheumatology · 2023Article
- Expression ofFuture virology · 2023Article
- Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect.Nucleic acids research · 2023Article
- Plasma Proteomics Unveil Novel Immune Signatures and Biomarkers upon SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration.International journal of molecular sciences · 2022Article
- Cellular immune states in SARS-CoV-2-induced disease.Frontiers in immunology · 2022Review
- A systems biology approach for investigating significantly expressed genes among COVID-19, hepatocellular carcinoma, and chronic hepatitis B.The Egyptian journal of medical human genetics · 2022Article
- Identification ofPharmacogenomics and personalized medicine · 2022Article
- Review
- Review
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11 authors.
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Abstract
As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues.
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