|
1
|
Alarcon PC, Ulanowicz CJ, Damen MSMA, Eom J, Sawada K, Chung H, Alahakoon T, Oates JR, Wayland JL, Stankiewicz TE, Moreno-Fernandez ME, Zacharias WJ, Salomonis N, Divanovic S. Obesity Uncovers the Presence of Inflammatory Lung Macrophage Subsets With an Adipose Tissue Transcriptomic Signature in Influenza Virus Infection. J Infect Dis 2025; 231:e317-e327. [PMID: 39494998 PMCID: PMC11841630 DOI: 10.1093/infdis/jiae535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 10/31/2024] [Indexed: 11/05/2024] Open
Abstract
Obesity is an independent risk factor for increased disease severity during influenza A virus (IAV) infection. White adipose tissue (WAT) inflammation promotes disease pathogenesis in obesity. Whether obesity modifies lung and WAT immune cells to amplify influenza severity is unknown. We show that obesity establishes a proinflammatory transcriptome in lung immune cells that is augmented during IAV infection and that IAV infection changes WAT immune cell milieu in obesity. Notably, a decrease in WAT macrophages (ATM) inversely correlates with an increase in infiltrating lung macrophages in obese IAV-infected mice. Further analyses of lung immune cell uncovered a macrophage subset that shares a transcriptomic signature with inflammatory ATMs. Importantly, adoptive transfer of ATMs from obese mice into lean IAV infected mice promotes host immune cell infiltration to the lungs. These findings suggest that, in an obese state, ATMs may exacerbate the inflammatory milieu important in pathologic responses to IAV infection.
Collapse
Affiliation(s)
- Pablo C Alarcon
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
- Medical Scientist Training Program, College of Medicine, University of Cincinnati, Ohio
| | - Cassidy J Ulanowicz
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
| | - Michelle S M A Damen
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
| | - John Eom
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
| | - Keisuke Sawada
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
- Medical Scientist Training Program, College of Medicine, University of Cincinnati, Ohio
| | - Hak Chung
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
| | - Tara Alahakoon
- Program in Biochemistry and Biophysics, Amherst College, Massachusetts
| | - Jarren R Oates
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
| | - Jennifer L Wayland
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
- Medical Scientist Training Program, College of Medicine, University of Cincinnati, Ohio
| | - Traci E Stankiewicz
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
| | - Maria E Moreno-Fernandez
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
| | - William J Zacharias
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Medical Scientist Training Program, College of Medicine, University of Cincinnati, Ohio
- Pulmonary Biology
| | - Nathan Salomonis
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Immunology Graduate Program
- Biomedical Informatics
| | - Senad Divanovic
- Department of Pediatrics, College of Medicine, University of Cincinnati
- Division of Immunobiology, Cincinnati Children's Hospital Medical Center
- Immunology Graduate Program
- Medical Scientist Training Program, College of Medicine, University of Cincinnati, Ohio
- Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Ohio
| |
Collapse
|
|
2
|
Xia B, Chen H, Taleb SJ, Xi X, Shaheen N, Baoyinna B, Soni S, Mebratu YA, Yount JS, Zhao J, Zhao Y. FBXL19 in endothelial cells protects the heart from influenza A infection by enhancing antiviral immunity and reducing cellular senescence programs. Am J Physiol Heart Circ Physiol 2024; 327:H937-H946. [PMID: 39150394 PMCID: PMC11482256 DOI: 10.1152/ajpheart.00371.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/25/2024] [Accepted: 08/15/2024] [Indexed: 08/17/2024]
Abstract
Influenza A virus (IAV) infection while primarily affecting the lungs, is often associated with cardiovascular complications. However, the mechanisms underlying this association are not fully understood. Here, we investigated the potential role of FBXL19, a member of the Skp1-Cullin-1-F-box family of E3 ubiquitin ligase, in IAV-induced cardiac inflammation. We demonstrated that FBXL19 overexpression in endothelial cells (ECs) reduced viral titers and IAV matrix protein 1 (M1) levels while increasing antiviral gene expression, including interferon (IFN)-α, -β, and -γ and RANTES (regulated on activation normal T cell expressed and secreted) in the cardiac tissue of IAV-infected mice. Moreover, EC-specific overexpression of FBXL19 attenuated the IAV infection-reduced interferon regulatory factor 3 (IRF3) level without altering its mRNA level and suppressed cardiac inflammation. Furthermore, IAV infection triggered cellular senescence programs in the heart as indicated by the upregulation of p16 and p21 mRNA levels and the downregulation of lamin-B1 levels, which were partially reversed by FBXL19 overexpression in ECs. Our findings indicate that EC-specific overexpression of FBXL19 protects against IAV-induced cardiac damage by enhancing interferon-mediated antiviral signaling, reducing cardiac inflammation, and suppressing cellular senescence programs.NEW & NOTEWORTHY Our study reveals a novel facet of IAV infection, demonstrating that it can trigger cellular senescence within the heart. Intriguingly, upregulation of endothelial FBXL19 promotes host innate immunity, reduces cardiac senescence, and diminishes inflammation. These findings highlight the therapeutic potential of targeting FBXL19 to mitigate IAV-induced cardiovascular complications.
Collapse
Affiliation(s)
- Boyu Xia
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Huilong Chen
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Sarah J Taleb
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Xiaoqing Xi
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Nargis Shaheen
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Boina Baoyinna
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
| | - Sourabh Soni
- Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
| | - Yohannes A Mebratu
- Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
| | - Jacob S Yount
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States
| | - Jing Zhao
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
- Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
| | - Yutong Zhao
- Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, United States
- Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States
| |
Collapse
|
|
3
|
Oshakbayev K, Durmanova A, Zhankalova Z, Idrisov A, Bedelbayeva G, Gazaliyeva M, Nabiyev A, Tordai A, Dukenbayeva B. Weight loss treatment for COVID-19 in patients with NCDs: a pilot prospective clinical trial. Sci Rep 2024; 14:10979. [PMID: 38744929 PMCID: PMC11094141 DOI: 10.1038/s41598-024-61703-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 05/08/2024] [Indexed: 05/16/2024] Open
Abstract
COVID-19 comorbid with noncommunicable chronic diseases (NCDs) complicates the diagnosis, treatment, and prognosis, and increases the mortality rate. The aim is to evaluate the effects of a restricted diet on clinical/laboratory inflammation and metabolic profile, reactive oxygen species (ROS), and body composition in patients with COVID-19 comorbid with NCDs. We conducted a 6-week open, pilot prospective controlled clinical trial. The study included 70 adult patients with COVID-19 comorbid with type 2 diabetes (T2D), hypertension, or nonalcoholic steatohepatitis (NASH). INTERVENTIONS a restricted diet including calorie restriction, hot water drinking, walking, and sexual self-restraint. PRIMARY ENDPOINTS COVID-19 diagnosis by detecting SARS-CoV-2 genome by RT-PCR; weight loss in Main group; body temperature; C-reactive protein. Secondary endpoints: the number of white blood cells; erythrocyte sedimentation rate; adverse effects during treatment; fasting blood glucose, glycosylated hemoglobin A1c (HbA1c), systolic/diastolic blood pressure (BP); blood lipids; ALT/AST, chest CT-scan. In Main group, patients with overweight lost weight from baseline (- 12.4%; P < 0.0001); 2.9% in Main group and 7.2% in Controls were positive for COVID-19 (RR: 0.41, CI: 0.04-4.31; P = 0.22) on the 14th day of treatment. Body temperature and C-reactive protein decreased significantly in Main group compared to Controls on day 14th of treatment (P < 0.025). Systolic/diastolic BP normalized (P < 0.025), glucose/lipids metabolism (P < 0.025); ALT/AST normalized (P < 0.025), platelets increased from baseline (P < 0.025), chest CT (P < 0.025) in Main group at 14 day of treatment. The previous antidiabetic, antihypertensive, anti-inflammatory, hepatoprotective, and other symptomatic medications were adequately decreased to completely stop during the weight loss treatment. Thus, the fast weight loss treatment may be beneficial for the COVID-19 patients with comorbid T2D, hypertension, and NASH over traditional medical treatment because, it improved clinical and laboratory/instrumental data on inflammation; glucose/lipid metabolism, systolic/diastolic BPs, and NASH biochemical outcomes, reactive oxygen species; and allowed patients to stop taking medications. TRIAL REGISTRATION ClinicalTrials.gov NCT05635539 (02/12/2022): https://clinicaltrials.gov/ct2/show/NCT05635539?term=NCT05635539&draw=2&rank=1 .
Collapse
Affiliation(s)
- Kuat Oshakbayev
- Internal Medicine Department, University Medical Center, Street Syganak, 46, 010000, Astana, Republic of Kazakhstan.
- ANADETO Medical Center, St. Kerey, Zhanibek Khans, 22, 010000, Astana, Republic of Kazakhstan.
| | - Aigul Durmanova
- Internal Medicine Department, University Medical Center, Street Syganak, 46, 010000, Astana, Republic of Kazakhstan
| | - Zulfiya Zhankalova
- Department of General Medical Practice, Asfendiyarov Kazakh National Medical University, #1, Street Tole Bi, 94, 050000, Almaty, Republic of Kazakhstan
| | - Alisher Idrisov
- Department of Endocrinology, Astana Medical University, Street Beibitshilik St 49/A, Astana, Republic of Kazakhstan
| | - Gulnara Bedelbayeva
- Faculty of Postgraduate Education, Asfendiyarov Kazakh National Medical University, Street Tole Bi, 94, 050000, Almaty, Republic of Kazakhstan
| | - Meruyert Gazaliyeva
- Faculty of Internal Medicine, Astana Medical University, Street Beibitshilik St 49/A, Astana, Republic of Kazakhstan
| | - Altay Nabiyev
- Internal Medicine Department, University Medical Center, Street Syganak, 46, 010000, Astana, Republic of Kazakhstan
| | - Attila Tordai
- Department of Transfusion Medicine, Semmelweis University, Vas U. 17, Budapest, 1088, Hungary
| | - Bibazhar Dukenbayeva
- Faculty of Pathology and Forensic Medicine, Astana Medical University, Astana, Republic of Kazakhstan
- ANADETO Medical Center, St. Kerey, Zhanibek Khans, 22, 010000, Astana, Republic of Kazakhstan
| |
Collapse
|
|
4
|
Kulasinghe A, Liu N, Tan CW, Monkman J, Sinclair JE, Bhuva DD, Godbolt D, Pan L, Nam A, Sadeghirad H, Sato K, Bassi GL, O'Byrne K, Hartmann C, Dos Santos Miggiolaro AFR, Marques GL, Moura LZ, Richard D, Adams M, de Noronha L, Baena CP, Suen JY, Arora R, Belz GT, Short KR, Davis MJ, Guimaraes FSF, Fraser JF. Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage. Immunology 2023; 168:403-419. [PMID: 36107637 PMCID: PMC9537957 DOI: 10.1111/imm.13577] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 09/12/2022] [Indexed: 12/15/2022] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.
Collapse
Affiliation(s)
- Arutha Kulasinghe
- Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Ning Liu
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Chin Wee Tan
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - James Monkman
- Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Jane E Sinclair
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
| | - Dharmesh D Bhuva
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - David Godbolt
- Pathology Queensland, The Prince Charles Hospital, Chermside, Queensland, Australia
| | - Liuliu Pan
- Nanostring Technologies, Inc, Seattle, Washington, USA
| | - Andy Nam
- Nanostring Technologies, Inc, Seattle, Washington, USA
| | - Habib Sadeghirad
- Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Kei Sato
- Critical Care Research Group, Faculty of Medicine, University of Queensland and The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Gianluigi Li Bassi
- Critical Care Research Group, Faculty of Medicine, University of Queensland and The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Ken O'Byrne
- The Princess Alexandra Hospital, Woolloongabba, Queensland, Australia
| | - Camila Hartmann
- Pontifical Catholic University of Parana, Curitiba, Brazil
- Marcelino Champagnat Hospital, Curitiba, Brazil
| | | | - Gustavo Lenci Marques
- Pontifical Catholic University of Parana, Curitiba, Brazil
- Marcelino Champagnat Hospital, Curitiba, Brazil
| | - Lidia Zytynski Moura
- Pontifical Catholic University of Parana, Curitiba, Brazil
- Marcelino Champagnat Hospital, Curitiba, Brazil
| | - Derek Richard
- Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Mark Adams
- Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
| | | | - Cristina Pellegrino Baena
- Pontifical Catholic University of Parana, Curitiba, Brazil
- Marcelino Champagnat Hospital, Curitiba, Brazil
| | - Jacky Y Suen
- Critical Care Research Group, Faculty of Medicine, University of Queensland and The Prince Charles Hospital, Brisbane, Queensland, Australia
| | - Rakesh Arora
- Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Gabrielle T Belz
- Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Kirsty R Short
- Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Melissa J Davis
- The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
- Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia
| | | | - John F Fraser
- Pathology Queensland, The Prince Charles Hospital, Chermside, Queensland, Australia
| |
Collapse
|
|
5
|
Markers of Infection-Mediated Cardiac Damage in Influenza and COVID-19. Pathogens 2022; 11:pathogens11101191. [PMID: 36297248 PMCID: PMC9607279 DOI: 10.3390/pathogens11101191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/18/2022] [Accepted: 10/13/2022] [Indexed: 11/07/2022] Open
Abstract
Introduction: Influenza and the coronavirus disease 2019 (COVID-19) are two potentially severe viral infections causing significant morbidity and mortality. The causative viruses, influenza A/B and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) can cause both pulmonary and extra-pulmonary disease, including cardiovascular involvement. The objective of this study was to determine the levels of cardiac biomarkers in hospitalized patients infected with influenza or COVID-19 and their correlation with secondary outcomes. Methods: We performed a retrospective comparative analysis of cardiac biomarkers in patients hospitalized at our department with influenza or COVID-19 by measuring high-sensitivity troponin-T (hs-TnT) and creatinine kinase (CK) in plasma. Secondary outcomes were intensive care unit (ICU) admission and all-cause in-hospital mortality. Results: We analyzed the data of 250 influenza patients and 366 COVID-19 patients. 58.6% of patients with influenza and 46.2% of patients with COVID-19 presented with increased hs-TnT levels. Patients of both groups with increased hs-TnT levels were significantly more likely to require ICU treatment or to die during their hospital stay. Compared with COVID-19, cardiac biomarkers were significantly higher in patients affected by influenza of all age groups, regardless of pre-existing cardiovascular disease. In patients aged under 65 years, no significant difference in ICU admission and mortality was detected between influenza and COVID-19, whereas significantly more COVID-19 patients 65 years or older died or required intensive care treatment. Conclusions: Our study shows that increased cardiac biomarkers are associated with higher mortality and ICU admission in both, influenza and SARS-CoV-2-infected patients. Cardiac biomarkers are higher in the influenza cohort; however, this does not translate into worse outcomes when compared with the COVID-19 cohort.
Collapse
|
|
6
|
Gao P, Ji M, Liu X, Chen X, Liu H, Li S, Jia B, Li C, Ren L, Zhao X, Wang Q, Bi Y, Tan X, Hou B, Zhou X, Tan W, Deng T, Wang J, Gao GF, Zhang F. Apolipoprotein E mediates cell resistance to influenza virus infection. SCIENCE ADVANCES 2022; 8:eabm6668. [PMID: 36129973 PMCID: PMC9491715 DOI: 10.1126/sciadv.abm6668] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 08/10/2022] [Indexed: 06/15/2023]
Abstract
Viruses exploit host cell machinery to support their replication. Defining the cellular proteins and processes required for a virus during infection is crucial to understanding the mechanisms of virally induced disease and designing host-directed therapeutics. Here, we perform a genome-wide CRISPR-Cas9-based screening in lung epithelial cells infected with the PR/8/NS1-GFP virus and use GFPhi cell as a unique screening marker to identify host factors that inhibit influenza A virus (IAV) infection. We discovered that APOE affects influenza virus infection both in vitro and in vivo. Cell deficiency in APOE conferred substantially increased susceptibility to IAV; mice deficient in APOE manifested more severe lung pathology, increased virus load, and decreased survival rate. Mechanistically, lack of cell-produced APOE results in impaired cell cholesterol homeostasis, enhancing influenza virus attachment. Thus, we identified a previously unrecognized role of APOE in restraining IAV infection.
Collapse
Affiliation(s)
- Ping Gao
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Miao Ji
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xinyuan Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaotong Chen
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Hongtao Liu
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shihua Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Baoqian Jia
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Chao Li
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lili Ren
- MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xin Zhao
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Qihui Wang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Yuhai Bi
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Xu Tan
- School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
| | - Baidong Hou
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Xuyu Zhou
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China
| | - Wenjie Tan
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Tao Deng
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
| | - Jianwei Wang
- MOH Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - George Fu Gao
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
| | - Fuping Zhang
- CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China
- Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101408, China
| |
Collapse
|
|
7
|
Froggatt HM, Heaton NS. Nonrespiratory sites of influenza-associated disease: mechanisms and experimental systems for continued study. FEBS J 2022; 289:4038-4060. [PMID: 35060315 PMCID: PMC9300775 DOI: 10.1111/febs.16363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 10/20/2021] [Accepted: 01/19/2022] [Indexed: 12/15/2022]
Abstract
The productive replication of human influenza viruses is almost exclusively restricted to cells in the respiratory tract. However, a key aspect of the host response to viral infection is the production of inflammatory cytokines and chemokines that are not similarly tissue restricted. As such, circulating inflammatory mediators, as well as the resulting activated immune cells, can induce damage throughout the body, particularly in individuals with underlying conditions. As a result, more holistic experimental approaches are required to fully understand the pathogenesis and scope of influenza virus-induced disease. This review summarizes what is known about some of the most well-appreciated nonrespiratory tract sites of influenza virus-induced disease, including neurological, cardiovascular, gastrointestinal, muscular and fetal developmental phenotypes. In the context of this discussion, we describe the in vivo experimental systems currently being used to study nonrespiratory symptoms. Finally, we highlight important future questions and potential models that can be used for a more complete understanding of influenza virus-induced disease.
Collapse
Affiliation(s)
- Heather M. Froggatt
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America
| | - Nicholas S. Heaton
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, United States of America
| |
Collapse
|
|
8
|
Xu Z, Forno E, Acosta-Pérez E, Han YY, Rosser F, Manni ML, Canino G, Chen W, Celedón JC. Differential gene expression in nasal airway epithelium from overweight or obese youth with asthma. Pediatr Allergy Immunol 2022; 33:e13776. [PMID: 35470932 PMCID: PMC9047012 DOI: 10.1111/pai.13776] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/07/2022] [Accepted: 04/09/2022] [Indexed: 12/21/2022]
Abstract
BACKGROUND The mechanisms underlying the known link between overweight/obesity and childhood asthma are unclear. We aimed to identify differentially expressed genes and pathways associated with obesity-related asthma through a transcriptomic analysis of nasal airway epithelium. METHODS We compared the whole transcriptome in nasal airway epithelium of youth with overweight or obesity and asthma with that of youth of normal weight and asthma, using RNA sequencing data from a cohort of 235 Puerto Ricans aged 9-20 years (EVA-PR) and an independent cohort of 66 children aged 6-16 years in Pittsburgh (VDKA). Differential expression analysis adjusting for age, sex, sequencing plate number, and sample sorting protocol, and the first five principal components were performed independently in each cohort. Results from the two cohorts were combined in a transcriptome-wide meta-analysis. Gene enrichment and network analyses were performed on top genes. RESULTS In the meta-analysis, 29 genes were associated with obesity-related asthma at an FDR-adjusted p <.05, including pro-inflammatory genes known to be differentially expressed in adipose tissue of obese subjects (e.g., CXCL11, CXCL10, and CXCL9) and several novel genes. Functional enrichment analyses showed that pathways for interferon signaling, and innate and adaptive immune responses were down-regulated in overweight/obese youth with asthma, while pathways related to ciliary structure or function were up-regulated. Upstream regulatory analysis predicted significant inhibition of the IRF7 pathway. Network analyses identified "hub" genes like GBP5 and SOCS1. CONCLUSION Our transcriptome-wide analysis of nasal airway epithelium identified biologically plausible genes and pathways for obesity-related asthma in youth.
Collapse
Affiliation(s)
- Zhongli Xu
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- School of Medicine, Tsinghua University, Beijing, China
| | - Erick Forno
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Edna Acosta-Pérez
- Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico, USA
| | - Yueh-Ying Han
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Franziska Rosser
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Michelle L Manni
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Glorisa Canino
- Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico, USA
| | - Wei Chen
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Juan C Celedón
- Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
9
|
Loosen SH, Jensen BEO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection 2022; 50:1165-1170. [PMID: 35355237 PMCID: PMC8966865 DOI: 10.1007/s15010-022-01784-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 02/04/2022] [Indexed: 12/12/2022]
Abstract
Purpose Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development. Methods We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS. Results Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28–1.65, p < 0.001) and obesity (OR 1.25, 95% CI 1.08–1.44, p = 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients’ age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54–2.13, p < 0.001), female sex (OR 1.33, 95% CI 1.20–1.47, p < 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39–2.00, p < 0.001) and depression (OR 1.27, 95% CI 1.09–1.47, p = < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09–1.95, p = < 0.012) in men were associated with an increased likelihood of developing LCS. Conclusion Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.
Collapse
Affiliation(s)
- Sven H Loosen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
| | - Björn-Erik Ole Jensen
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany
| | - Christian Tanislav
- Department of Geriatrics and Neurology, Diakonie Hospital Jung Stilling, Siegen, Germany
| | - Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
| | - Christoph Roderburg
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany.
| | | |
Collapse
|
|
10
|
Ibrahim Alhazmi A, Saleh Al-Sowayan N. Treatment and Prevention of Viral Infections through Nutrition and Strengthened Immunity: The COVID-19 Pandemic Case Scenario. Pak J Biol Sci 2022; 25:106-111. [PMID: 35233998 DOI: 10.3923/pjbs.2022.106.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The cause of the ongoing massive pandemic, the SARS-CoV-2 virus, originated in Wuhan, China and spread rapidly worldwide. The pandemic has helped identify the difficulties associated with devising best practices necessary to augment the immune system to prevent the contraction of viral infections, as well as enhance the process of recovery if an infection does occur. Medical scholars and researchers have been actively assessing dietary aspects that may improve the health of immune systems. It is already well-established that malnourishment can lead to increased oxidative stress and cause inflammation. Such conditions weaken the immune system and make people vulnerable to bacterial and infectious illnesses. In the current scenario, scientists have confirmed that some dietary components can enhance immunity in COVID-19 patients. Empirical evidence suggested that the condition of COVID-19 patients is largely attributable to increased metabolic rates that drain the body's glucose supplies. This highlights the necessity of improving the quality of enteral nutrition provided to COVID-19 patients. Despite being dietarily sensitive, these individuals require regular monitoring and assessments to discern their nutritional deficiencies. In general, the diet should include foodstuffs with anti-inflammatory properties and micronutrients, including polyphenols, carotenoids, vitamin C, vitamin E, etc. Considering nutrition in the overall treatment provided will greatly fortify the immunity of COVID-19 patients and increase the probability of survival.
Collapse
|
|
11
|
Hulme KD, Noye EC, Short KR, Labzin LI. Dysregulated Inflammation During Obesity: Driving Disease Severity in Influenza Virus and SARS-CoV-2 Infections. Front Immunol 2021; 12:770066. [PMID: 34777390 PMCID: PMC8581451 DOI: 10.3389/fimmu.2021.770066] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 09/30/2021] [Indexed: 12/15/2022] Open
Abstract
Acute inflammation is a critical host defense response during viral infection. When dysregulated, inflammation drives immunopathology and tissue damage. Excessive, damaging inflammation is a hallmark of both pandemic influenza A virus (IAV) infections and Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Chronic, low-grade inflammation is also a feature of obesity. In recent years, obesity has been recognized as a growing pandemic with significant mortality and associated costs. Obesity is also an independent risk factor for increased disease severity and death during both IAV and SARS-CoV-2 infection. This review focuses on the effect of obesity on the inflammatory response in the context of viral respiratory infections and how this leads to increased viral pathology. Here, we will review the fundamentals of inflammation, how it is initiated in IAV and SARS-CoV-2 infection and its link to disease severity. We will examine how obesity drives chronic inflammation and trained immunity and how these impact the immune response to IAV and SARS-CoV-2. Finally, we review both medical and non-medical interventions for obesity, how they impact on the inflammatory response and how they could be used to prevent disease severity in obese patients. As projections of global obesity numbers show no sign of slowing down, future pandemic preparedness will require us to consider the metabolic health of the population. Furthermore, if weight-loss alone is insufficient to reduce the risk of increased respiratory virus-related mortality, closer attention must be paid to a patient’s history of health, and new therapeutic options identified.
Collapse
Affiliation(s)
- Katina D Hulme
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Ellesandra C Noye
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Kirsty R Short
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.,Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia
| | - Larisa I Labzin
- Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia.,Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| |
Collapse
|
|
12
|
Alarcon PC, Damen MSMA, Madan R, Deepe GS, Spearman P, Way SS, Divanovic S. Adipocyte inflammation and pathogenesis of viral pneumonias: an overlooked contribution. Mucosal Immunol 2021; 14:1224-1234. [PMID: 33958704 PMCID: PMC8100369 DOI: 10.1038/s41385-021-00404-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/18/2021] [Accepted: 03/27/2021] [Indexed: 02/06/2023]
Abstract
Epidemiological evidence establishes obesity as an independent risk factor for increased susceptibility and severity to viral respiratory pneumonias associated with H1N1 influenza and SARS-CoV-2 pandemics. Given the global obesity prevalence, a better understanding of the mechanisms behind obese susceptibility to infection is imperative. Altered immune cell metabolism and function are often perceived as a key causative factor of dysregulated inflammation. However, the contribution of adipocytes, the dominantly altered cell type in obesity with broad inflammatory properties, to infectious disease pathogenesis remains largely ignored. Thus, skewing of adipocyte-intrinsic cellular metabolism may lead to the development of pathogenic inflammatory adipocytes, which shape the overall immune responses by contributing to either premature immunosenescence, delayed hyperinflammation, or cytokine storm in infections. In this review, we discuss the underappreciated contribution of adipocyte cellular metabolism and adipocyte-produced mediators on immune system modulation and how such interplay may modify disease susceptibility and pathogenesis of influenza and SARS-CoV-2 infections in obese individuals.
Collapse
Affiliation(s)
- Pablo C Alarcon
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Divisions of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Medical Scientist Training Program, Cincinnati, OH, USA
- Immunology Graduate Program Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Michelle S M A Damen
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Divisions of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Rajat Madan
- Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Veterans Affairs Medical Center, Cincinnati, OH, USA
| | - George S Deepe
- Division of Infectious Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Paul Spearman
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Sing Sing Way
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
- Divisions of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
| | - Senad Divanovic
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
- Divisions of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
- Medical Scientist Training Program, Cincinnati, OH, USA.
- Immunology Graduate Program Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA.
- Center for Inflammation and Tolerance, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
| |
Collapse
|
|
13
|
Sinclair JE, Bloxham CJ, Chiu H, Chew KY, Russell J, Yoshikawa Y, Bielefeldt-Ohmann H, Steele LE, Hulme KD, Verzele NA, Noye EC, Wu M, Reichelt ME, Thomas WG, Gallo LA, Redd MA, Short KR. Type I Diabetes Mellitus Increases the Cardiovascular Complications of Influenza Virus Infection. Front Cell Infect Microbiol 2021; 11:714440. [PMID: 34595130 PMCID: PMC8476859 DOI: 10.3389/fcimb.2021.714440] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/30/2021] [Indexed: 01/01/2023] Open
Abstract
People with diabetes mellitus are susceptible to both cardiovascular disease and severe influenza A virus infection. We hypothesized that diabetes also increases risks of influenza-associated cardiac complications. A murine type 1 (streptozotocin-induced) diabetes model was employed to investigate influenza-induced cardiac distress. Lung histopathology and viral titres revealed no difference in respiratory severity between infected control and diabetic mice. However, compared with infected control mice, infected diabetic mice had increased serum cardiac troponin I and creatine-kinase MB, left ventricular structural changes and right ventricular functional alterations, providing the first experimental evidence of type I diabetes increasing risks of influenza-induced cardiovascular complications.
Collapse
Affiliation(s)
- Jane E Sinclair
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Conor J Bloxham
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Han Chiu
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Keng Yih Chew
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Jake Russell
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Yusuke Yoshikawa
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Helle Bielefeldt-Ohmann
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.,School of Veterinary Science, The University of Queensland, Brisbane, QLD, Australia
| | - Lauren E Steele
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Katina D Hulme
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Nathalie Aj Verzele
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Ellesandra C Noye
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Melanie Wu
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Melissa E Reichelt
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Walter G Thomas
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Linda A Gallo
- School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia
| | - Meredith A Redd
- Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
| | - Kirsty R Short
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| |
Collapse
|
|
14
|
Yin M, Zhang L, Tang S, Matsuoka R, Xi Y, Tao N, Wang X. Egg Yolk Phospholipids Modulate Microbial Imbalance in the Intestinal Tract of Rats on a High‐Fructose Diet. EUR J LIPID SCI TECH 2021. [DOI: 10.1002/ejlt.202100131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Mingyu Yin
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
- College of Fisheries and Life Science Shanghai Ocean University Shanghai 201306 China
- Shanghai Engineering Research Center of Aquatic‐Product Processing and Preservation Shanghai 201306 China
| | - Long Zhang
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
- College of Fisheries and Life Science Shanghai Ocean University Shanghai 201306 China
- Shanghai Engineering Research Center of Aquatic‐Product Processing and Preservation Shanghai 201306 China
| | - Shijie Tang
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
- College of Fisheries and Life Science Shanghai Ocean University Shanghai 201306 China
| | - Ryosuke Matsuoka
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
| | - Yinci Xi
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
| | - Ningping Tao
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
- College of Fisheries and Life Science Shanghai Ocean University Shanghai 201306 China
| | - Xichang Wang
- College of Food Science and Technology Shanghai Ocean University Shanghai 201306 China
- College of Fisheries and Life Science Shanghai Ocean University Shanghai 201306 China
- Shanghai Engineering Research Center of Aquatic‐Product Processing and Preservation Shanghai 201306 China
| |
Collapse
|
|
15
|
Vargas-Mendoza N, García-Machorro J, Angeles-Valencia M, Martínez-Archundia M, Madrigal-Santillán EO, Morales-González Á, Anguiano-Robledo L, Morales-González JA. Liver disorders in COVID-19, nutritional approaches and the use of phytochemicals. World J Gastroenterol 2021; 27:5630-5665. [PMID: 34629792 PMCID: PMC8473593 DOI: 10.3748/wjg.v27.i34.5630] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/19/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.
Collapse
Affiliation(s)
- Nancy Vargas-Mendoza
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | - Jazmín García-Machorro
- Laboratorio de Medicina de Conservacion, Instituto Politécnico Nacional, México 11340, Mexico
| | | | - Marlet Martínez-Archundia
- Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotécnológica, Instituto Politécnico Nacional, México 11340, Mexico
| | | | | | | | - José A Morales-González
- Laboratorio Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México 11340, Mexico
| |
Collapse
|
|
16
|
Longmore DK, Miller JE, Bekkering S, Saner C, Mifsud E, Zhu Y, Saffery R, Nichol A, Colditz G, Short KR, Burgner DP. Diabetes and Overweight/Obesity Are Independent, Nonadditive Risk Factors for In-Hospital Severity of COVID-19: An International, Multicenter Retrospective Meta-analysis. Diabetes Care 2021; 44:1281-1290. [PMID: 33858854 PMCID: PMC8247499 DOI: 10.2337/dc20-2676] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/14/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Obesity is an established risk factor for severe coronavirus disease 2019 (COVID-19), but the contribution of overweight and/or diabetes remains unclear. In a multicenter, international study, we investigated if overweight, obesity, and diabetes were independently associated with COVID-19 severity and whether the BMI-associated risk was increased among those with diabetes. RESEARCH DESIGN AND METHODS We retrospectively extracted data from health care records and regional databases of hospitalized adult patients with COVID-19 from 18 sites in 11 countries. We used standardized definitions and analyses to generate site-specific estimates, modeling the odds of each outcome (supplemental oxygen/noninvasive ventilatory support, invasive mechanical ventilatory support, and in-hospital mortality) by BMI category (reference, overweight, obese), adjusting for age, sex, and prespecified comorbidities. Subgroup analysis was performed on patients with preexisting diabetes. Site-specific estimates were combined in a meta-analysis. RESULTS Among 7,244 patients (65.6% overweight/obese), those with overweight were more likely to require oxygen/noninvasive ventilatory support (random effects adjusted odds ratio [aOR], 1.44; 95% CI 1.15-1.80) and invasive mechanical ventilatory support (aOR, 1.22; 95% CI 1.03-1.46). There was no association between overweight and in-hospital mortality (aOR, 0.88; 95% CI 0.74-1.04). Similar effects were observed in patients with obesity or diabetes. In the subgroup analysis, the aOR for any outcome was not additionally increased in those with diabetes and overweight or obesity. CONCLUSIONS In adults hospitalized with COVID-19, overweight, obesity, and diabetes were associated with increased odds of requiring respiratory support but were not associated with death. In patients with diabetes, the odds of severe COVID-19 were not increased above the BMI-associated risk.
Collapse
Affiliation(s)
- Danielle K Longmore
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia .,Menzies School of Health Research, Charles Darwin University, Darwin, Australia.,Infectious Diseases Unit, Department of General Medicine, The Royal Children's Hospital, Parkville, Victoria, Australia
| | - Jessica E Miller
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.,Department of Paediatrics, Melbourne University, Parkville, Victoria, Australia
| | - Siroon Bekkering
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.,Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Christoph Saner
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.,Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Hospital Inselspital, University of Bern, Bern, Switzerland
| | - Edin Mifsud
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.,World Health Organization Collaborating Centre for Reference and Research on Influenza, Doherty Institute, Melbourne, Australia
| | - Yanshan Zhu
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia
| | - Richard Saffery
- Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.,Department of Paediatrics, Melbourne University, Parkville, Victoria, Australia
| | - Alistair Nichol
- Department of Intensive Care, Alfred Health, Melbourne, Australia.,Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.,University College Dublin Clinical Research Centre, St Vincent's Hospital, Dublin, Ireland
| | | | - Kirsty R Short
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia
| | | | | | | |
Collapse
|
|
17
|
Veldhuis Kroeze E, Bauer L, Caliendo V, van Riel D. In Vivo Models to Study the Pathogenesis of Extra-Respiratory Complications of Influenza A Virus Infection. Viruses 2021; 13:v13050848. [PMID: 34066589 PMCID: PMC8148586 DOI: 10.3390/v13050848] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/30/2021] [Accepted: 05/03/2021] [Indexed: 12/14/2022] Open
Abstract
Animal models are an inimitable method to study the systemic pathogenesis of virus-induced disease. Extra-respiratory complications of influenza A virus infections are not extensively studied even though they are often associated with severe disease and mortality. Here we review and recommend mammalian animal models that can be used to study extra-respiratory complications of the central nervous system and cardiovascular system as well as involvement of the eye, placenta, fetus, lacteal gland, liver, pancreas, intestinal tract, and lymphoid tissues during influenza A virus infections.
Collapse
|
|
18
|
Bohlouli J, Moravejolahkami AR, Ganjali Dashti M, Balouch Zehi Z, Hojjati Kermani MA, Borzoo-Isfahani M, Bahreini-Esfahani N. COVID-19 and Fast Foods Consumption: a Review. INTERNATIONAL JOURNAL OF FOOD PROPERTIES 2021. [DOI: 10.1080/10942912.2021.1873364] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Jalal Bohlouli
- Department of Nutrition, Nutrition and Food Security Research Centre, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amir Reza Moravejolahkami
- Department of Clinical Nutrition, School of Nutrition & Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marjan Ganjali Dashti
- Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA
| | - Zakiyeh Balouch Zehi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ali Hojjati Kermani
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Borzoo-Isfahani
- Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nimah Bahreini-Esfahani
- Department of Food Science and Technology, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| |
Collapse
|
|
19
|
Iddir M, Brito A, Dingeo G, Fernandez Del Campo SS, Samouda H, La Frano MR, Bohn T. Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis. Nutrients 2020; 12:E1562. [PMID: 32471251 PMCID: PMC7352291 DOI: 10.3390/nu12061562] [Citation(s) in RCA: 447] [Impact Index Per Article: 89.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 05/21/2020] [Accepted: 05/25/2020] [Indexed: 12/13/2022] Open
Abstract
The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.
Collapse
Affiliation(s)
- Mohammed Iddir
- Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; (M.I.); or (A.B.); (S.S.F.D.C.); (H.S.)
| | - Alex Brito
- Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; (M.I.); or (A.B.); (S.S.F.D.C.); (H.S.)
- Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology. I.M. Sechenov First Moscow Medical University, Trubetskay Str. 8, 119991 Moscow, Russia
| | - Giulia Dingeo
- Independent Researcher, Val de Marne, 94999 Paris, France;
| | - Sofia Sosa Fernandez Del Campo
- Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; (M.I.); or (A.B.); (S.S.F.D.C.); (H.S.)
| | - Hanen Samouda
- Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; (M.I.); or (A.B.); (S.S.F.D.C.); (H.S.)
| | - Michael R. La Frano
- Department of Food Science and Nutrition, California Polytechnic State University, 1 Grand Avenue, San Luis Obispo, CA 93407, USA;
- Center for Health Research, California Polytechnic State University, 1 Grand Avenue, San Luis Obispo, CA 93407, USA
| | - Torsten Bohn
- Nutrition and Health Research Group, Population Health Department, Luxembourg Institute of Health, 1A-B, rue Thomas Edison, L-1445 Strassen, Luxembourg; (M.I.); or (A.B.); (S.S.F.D.C.); (H.S.)
| |
Collapse
|