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Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients.
Hammoudeh, Sarah Musa; Hammoudeh, Arabella Musa; Bhamidimarri, Poorna Manasa; Al Safar, Habiba; Mahboub, Bassam; Künstner, Axel; Busch, Hauke; Halwani, Rabih; Hamid, Qutayba; Rahmani, Mohamed; Hamoudi, Rifat.
Afiliação
  • Hammoudeh SM; Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Hammoudeh AM; Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany.
  • Bhamidimarri PM; Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Al Safar H; General Surgery Department, Tawam Hospital, SEHA, Al Ain, United Arab Emirates.
  • Mahboub B; Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Künstner A; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • Busch H; Department of Genetics and Molecular Biology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • Halwani R; Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Hamid Q; Department of Respiratory Medicine, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
  • Rahmani M; Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany.
  • Hamoudi R; Luebeck Institute of Experimental Dermatology, University of Luebeck, Luebeck, Germany.
Front Immunol ; 12: 595150, 2021.
Article em En | MEDLINE | ID: mdl-34262555
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Índice de Gravidade de Doença / Pandemias / SARS-CoV-2 / COVID-19 / Rim / Fígado / Pulmão / Miocárdio Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Front Immunol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Emirados Árabes Unidos País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Índice de Gravidade de Doença / Pandemias / SARS-CoV-2 / COVID-19 / Rim / Fígado / Pulmão / Miocárdio Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Front Immunol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Emirados Árabes Unidos País de publicação: Suíça