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Félix P, Melo AA, Costa JP, Colaço M, Pereira D, Núñez J, de Almeida LP, Borges O. Exploring TLR agonists as adjuvants for COVID-19 oral vaccines. Vaccine 2025; 53:127078. [PMID: 40184639 DOI: 10.1016/j.vaccine.2025.127078] [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: 01/15/2025] [Revised: 03/18/2025] [Accepted: 03/27/2025] [Indexed: 04/07/2025]
Abstract
The COVID-19 pandemic underscored the importance of advancing technologies that enable the rapid development and distribution of more effective vaccines when required. Since SARS-CoV-2 enters the body through the nasal mucosa, optimising the induction of secretory IgA (sIgA) production, a key component of the mucosal immune response, is essential. It has long been known that the induction of sIgA occurs when a vaccine is administered through mucosal surfaces and the immune responses initiated at one mucosal site can influence immune activity at other mucosal surfaces. Consequently, we propose an oral vaccine formulation (Vacform) comprising the immunomodulator CL097, a TLR7/8 agonist, and the SARS-CoV-2 spike protein, both encapsulated within glucan particles (GPs). The studies demonstrated that Vacform induced ROS production in RAW 264.7 cells but not in human neutrophils. The concentrations of Vacform tested did not induce NO production in RAW 264.7 cells. While Vacform stimulated the production of TNF-α and IL-6 in mouse spleen cells, this effect was not observed in RAW 264.7 cells. Finally, Vacform stimulated the proliferation of human PBMCs. Thus, its immunomodulatory properties were evident in specific cells under certain in vitro conditions. The Vacform was subsequently tested in vaccination studies. C57BL/6 mice were initially immunized subcutaneously, followed by two oral boosts with Vacform every two weeks. The Vacform elicited both, humoral (serum IgG and mucosal sIgA) and cellular immune responses. A balanced Th1/Th2/Th17 immune profile was observed. In conclusion, the GPs:CL097 adjuvant system shows promise for eliciting robust immune responses against SARS-CoV-2 and provides a foundation for future studies on dose-response optimization and challenge models.
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Affiliation(s)
- Paulo Félix
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Alexandra A Melo
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - João Panão Costa
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Mariana Colaço
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal
| | - Dina Pereira
- Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal; IIIUC - Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal
| | - Jisette Núñez
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal
| | - Luís Pereira de Almeida
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal; Gene Therapy Center of Excellence (GeneT), Coimbra 3004-504, Portugal
| | - Olga Borges
- Faculty of Pharmacy (FFUC), University of Coimbra, 3000-548 Coimbra, Portugal; Centre for Innovation in Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra 3004-504, Portugal; Centre for Neuroscience and Cell Biology - University of Coimbra (CNC - UC), Coimbra 3004-504, Portugal.
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Xu J, Yu Y, Li S, Qiu F. Global Trends in Research of Amino Acid Metabolism in T Lymphocytes in Recent 15 Years: A Bibliometric Analysis. J Immunol Res 2025; 2025:3393342. [PMID: 39950085 PMCID: PMC11824865 DOI: 10.1155/jimr/3393342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 12/20/2024] [Indexed: 02/16/2025] Open
Abstract
Amino acid metabolism in T cells determines the therapeutic efficacy of T-cell-targeting drugs. To assess the direction of amino acid metabolism in T cells and construct related knowledge structure, we performed a bibliometric analysis aiming at amino acid metabolism in T cells utilizing studies publicized in recent 15 years. Three hundred thirty-seven related studies were downloaded from the Web of Science Core Collection (WoSCC), and the information on countries, institutes, and authors was collected and analyzed. In addition, the present research status and future trends were explored according to the results yielded from the analysis of cited references and keywords. This study revealed that publications regarding amino acid metabolism in T cells gradually increased each year. The USA is the top producer and most influential country in this field. Recent research has focused on the correlation between the metabolism of several amino acids and regulatory T cells (Tregs) and CD8+ T cells. Overall, this research offers a comprehensive exhibition on the field of amino acid metabolism in T cells, which will help researchers to study this domain more effectively and intuitively.
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Affiliation(s)
- Jiaona Xu
- Department of Rehabilitation, Hangzhou Geriatric Hospital, Hangzhou 310022, China
| | - Yinan Yu
- Department of Rehabilitation, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou 310006, China
| | - Shijie Li
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310018, China
| | - Fanghui Qiu
- Department of Rehabilitation, Hangzhou Geriatric Hospital, Hangzhou 310022, China
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Wu Y, He L, Li R, Li J, Zhao Q, Shao B. A20 as a Potential Therapeutic Target for COVID-19. Immun Inflamm Dis 2025; 13:e70127. [PMID: 39853876 PMCID: PMC11760982 DOI: 10.1002/iid3.70127] [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: 04/12/2024] [Revised: 11/29/2024] [Accepted: 01/03/2025] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major concern due to its astonishing prevalence and high fatality rate, especially among elderly people. Patients suffering from COVID-19 may exhibit immunosuppression in the initial stage of infection, while a cytokine storm can occur when the disease progresses to a severe stage. This inopportune immune rhythm not only makes patients more susceptible to the virus but also leads to numerous complications resulting from the excessive production of inflammatory factors. A20, which is widely accepted as a pivotal regulator of inflammation, has been shown to be implicated in the processes of antiviral responses and immunosuppression. Thus, A20 may participate in regulating the pathological processes of COVID-19. METHODS This narrative literature review summarizes recent evidence on the mechanisms of A20 in regulating the pathological processes of COVID-19. We also downloaded single-cell RNA-seq data sets from healthy individuals and patients with varying severities of COVID-19 from the NCBI GEO database to further dissect A20's regulatory mechanisms of these intricate cytokine pathways that are closely associated with SARS-CoV-2 infection. RESULTS A20 might be one of the most critical anti-infectious and anti-inflammatory factors involved in the pathogenesis of COVID-19. It effectively suppresses the immune damage and inflammatory storm caused by viral infection. CONCLUSIONS Understanding the relationship between A20-regulated signaling pathways and pathological processes of COVID-19 can provide insight into potential targets for intervention. Precise regulation of A20 to induce antiviral activity and an anti-inflammatory response could mediate the pathogenesis of COVID-19 and could become an effective treatment.
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Affiliation(s)
- Yongyao Wu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Lilan He
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Rong Li
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Jiuxuan Li
- Laboratory of Radiation Biology, Laboratory Medicine Centre, Department of Blood TransfusionThe Second Affiliated HospitalArmy Military Medical UniversityChongqingChina
| | - Qing Zhao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
| | - Bin Shao
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of StomatologySichuan UniversityChengduChina
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Subbarayan K, Al-Samadi A, Schäfer H, Massa C, Salo T, Biehl K, Vaxevanis CK, Ulagappan K, Wahbi W, Reimers M, Drexler F, Moreira-Soto A, Bachmann M, Seliger B. Altered ACE2 and interferon landscape in the COVID-19 microenvironment correlate with the anti-PD-1 response in solid tumors. Cell Mol Life Sci 2024; 81:473. [PMID: 39625479 PMCID: PMC11615173 DOI: 10.1007/s00018-024-05520-9] [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: 06/21/2024] [Revised: 10/03/2024] [Accepted: 11/18/2024] [Indexed: 12/06/2024]
Abstract
Angiotensensin-converting enzyme-2 (ACE2) is a receptor for SARS-CoV-2, allowing the virus to enter cells. Although tumor patients infected by SARS-CoV-2 often have a worse outcome, the expression, function and clinical relevance of ACE2 in tumors has not yet been thoroughly analyzed. In this study, RNA sequencing (RNA-seq) data from tumors, adjacent tissues and whole blood samples of COVID-19 patients from genome databases and from tumor cell lines and endothelial cells infected with different SARS-CoV-2 variants or transfected with an ACE2 expression vector (ACE2high) or mock (ACE2low) were analyzed for the expression of ACE2 and immune response relevant molecules in silico or by qPCR, flow cytometry, Western blot and/or RNA-seq. The differential expression profiles in ACE2high vs. ACE2low cells correlated with available SARS-CoV-2 RNA-seq datasets. ACE2high cells demonstrated upregulated mRNA and/or protein levels of HLA class I, programmed death ligand 1 (PD-L1), components of the antigen processing machinery (APM) and the interferon (IFN) signaling pathway compared to ACE2low cells. Co-cultures of ACE2high cells with peripheral blood mononuclear cells increased immune cell migration and infiltration towards ACE2high cells, apoptosis of ACE2high cells, release of innate immunity-related cytokines and altered NK cell-mediated cytotoxicity. Thus, ACE2 expression was associated in different model systems and upon SARS-CoV-2 infection with an altered host immunogenicity, which might influence the efficacy of immune checkpoint inhibitors. These results provide novel insights into the (patho)physiological role of ACE2 on immune response-relevant mechanisms and suggest an alternative strategy to reduce COVID-19 severity in infected tumor patients targeting the ACE2-induced IFN-PD-L1 axis.
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Affiliation(s)
- Karthikeyan Subbarayan
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | - Ahmed Al-Samadi
- Institute of Dentistry, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Joensuu, Finland
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
| | - Helene Schäfer
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | - Chiara Massa
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
- Institute of Translational Immunology, Brandenburg an der Havel, Germany
| | - Tuula Salo
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
- Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, 90014, Finland
| | - Katharina Biehl
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | - Christoforos K Vaxevanis
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | - Kamatchi Ulagappan
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | - Wafa Wahbi
- Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
| | - Matthias Reimers
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany
| | | | | | - Michael Bachmann
- Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
| | - Barbara Seliger
- Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Str. 2, 06112, Halle (Saale), Germany.
- Institute of Translational Immunology, Brandenburg an der Havel, Germany.
- Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
- Institute of Translational Medicine, Medical School Theodor Fontane, Hochstr. 29, 14770, Brandenburg an der Havel, Germany.
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Son S, Jin S, Hong JY, Shin JM, Jung KE, Seo YJ, Kim CD, Hong D, Lee Y. Clinical Manifestation of Alopecia Areata After COVID-19 Infection or Vaccination. Ann Dermatol 2024; 36:361-366. [PMID: 39623612 PMCID: PMC11621643 DOI: 10.5021/ad.24.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 02/05/2024] [Accepted: 02/13/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND Alopecia areata (AA) is characterized by an autoimmune inflammatory response to hair follicles. Several studies have suggested that infection and vaccination can trigger an autoimmune process around hair follicles. Moreover, reports of AA and various other autoimmune diseases have increased since the coronavirus disease 2019 (COVID-19) pandemic became established. OBJECTIVE We assessed the clinical characteristics and treatment response in patients who developed AA following COVID-19 infection or vaccination. METHODS This retrospective study involved patients who had developed COVID-19 or received a COVID-19 vaccination within 3 months before the onset or aggravation of AA from January 2020 to December 2022. RESULTS Fifty patients met the inclusion criteria. Eighteen patients had a history of COVID-19 infection, and 32 had a history of COVID-19 vaccination. The mean onset of AA after COVID-19 infection and vaccination was 5.22±3.35 and 4.13±2.73 weeks, respectively. The most common COVID-19-associated symptoms before AA were fever (88.9%) in the infection group and myalgia (50.0%) in the vaccination group. In the vaccination group, AA most commonly occurred after receiving the Pfizer-BioNTech vaccine (BNT162b2, 46.9%) or Moderna vaccine (mRNA-1273, 34.4%). The vaccination group showed more rapid improvement than the infection group; however, both showed significant improvement after 6 months of treatment of AA. CONCLUSION We examined the clinical characteristics and treatment responses of patients who developed AA after COVID-19 infection or vaccination. Further research is needed to evaluate the detailed pathogenesis and association between COVID-19 and AA.
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Affiliation(s)
- Seungjin Son
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Soyoung Jin
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Ji Yeon Hong
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Jung-Min Shin
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Kyung Eun Jung
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Young-Joon Seo
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Chang-Deok Kim
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Dongkyun Hong
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea.
| | - Young Lee
- Department of Dermatology, Chungnam National University School of Medicine, Daejeon, Korea.
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Zheng YB, Lu S, Chu TB, Pang GF, Yang LY, Zhang Q. Investigate the potential impact of Hemagglutinin from the H1N1 strain on severe pneumonia. Gene 2024; 926:148559. [PMID: 38740352 DOI: 10.1016/j.gene.2024.148559] [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: 01/20/2024] [Revised: 05/03/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
The most prevalent glycoprotein on the influenza virus envelope is called hemagglutinin (HA), yet little is known about its involvement in the pathophysiology and etiology of severe influenza pneumonia. Here, after stimulating human bronchial epithelial cells (16-HBE) and mice with HA of H1N1 for 12 h, we investigated the proliferation, migration, inflammatory cytokines expression, and apoptosis in 16-HBE and the pathological damage in mouse lung tissue. The expression of inflammatory cytokines plasminogen activator inhibitor 1(PAI-1), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators, and apoptosis were all enhanced by HA, which also prevented the proliferation and migration of bronchial epithelial cells. HA enhanced up-regulated PAI-1, uPA, and tPA protein expression within mouse lung tissue and caused lung injury. In conclusion, HA alone, but not the whole H1N1 virus, induces lung tissue injury by inhibiting cell proliferation and migration, while promoting the expression of inflammatory cytokines and apoptosis.
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Affiliation(s)
- Yu-Bi Zheng
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China.
| | - Song Lu
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China
| | - Tian-Bao Chu
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China
| | - Gui-Feng Pang
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China
| | - Lin-Ying Yang
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China
| | - Qing Zhang
- Affiliated Hospital of Chengde Medical University, Department of Respiratory and Critical Care Medicine, Chengde 067000, Hebei, China.
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Niu C, Liang T, Chen Y, Zhu S, Zhou L, Chen N, Qian L, Wang Y, Li M, Zhou X, Cui J. SARS-CoV-2 spike protein induces the cytokine release syndrome by stimulating T cells to produce more IL-2. Front Immunol 2024; 15:1444643. [PMID: 39359733 PMCID: PMC11445618 DOI: 10.3389/fimmu.2024.1444643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 08/13/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction Cytokine release syndrome (CRS) is one of the leading causes of mortality in patients with COVID-19 caused by the SARS-CoV-2 coronavirus. However, the mechanism of CRS induced by SARS-CoV-2 is vague. Methods Using spike protein combined with IL-2, IFN-γ, and TNF-α to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete CRS-related cytokines, the content of cytokines in the supernatant was detected, and the effects of NK, T, and monocytes were analyzed. Results This study shows that dendritic cells loaded with spike protein of SARS-CoV-2 stimulate T cells to release much more interleukin-2 (IL-2,) which subsequently cooperates with spike protein to facilitate PBMCs to release IL-1β, IL-6, and IL-8. These effects are achieved via IL-2 stimulation of NK cells to release tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), as well as T cells to release IFN-γ Mechanistically, IFN-γ and TNF-α enhance the transcription of CD40, and the interaction of CD40 and its ligand stabilizes the membrane expression of toll-like receptor 4 (TLR4) that serves as a receptor of spike protein on the surface of monocytes. As a result, there is a constant interaction between spike protein and TLR4, leading to continuous activation of nuclear factor-κ-gene binding (NF-κB). Furthermore, TNF-α also activates NF-κB signaling in monocytes, which further cooperates with IFN-γ and spike protein to modulate NF-κB-dependent transcription of CRS-related inflammatory cytokines. Discussion Targeting TNF-α/IFN-γ in combination with TLR4 may represent a promising therapeutic approach for alleviating CRS in individuals with COVID-19.
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Affiliation(s)
- Chao Niu
- Cancer Center, The First Hospital of Jilin University, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
| | - Tingting Liang
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Yongchong Chen
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Shan Zhu
- Cancer Center, The First Hospital of Jilin University, Changchun, China
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China
| | - Lei Zhou
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Naifei Chen
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Lei Qian
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Yufeng Wang
- Cancer Center, The First Hospital of Jilin University, Changchun, China
- Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, China
| | - Min Li
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Xin Zhou
- Cancer Center, The First Hospital of Jilin University, Changchun, China
- International Center of Future Science, Jilin University, Changchun, China
- Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, China
| | - Jiuwei Cui
- Cancer Center, The First Hospital of Jilin University, Changchun, China
- Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, China
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Xie E, Shen X, Yeo YH, Xing Z, Ebinger JE, Duan Y, Zhang Y, Cheng S, Ji F, Deng J. Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2024; 44:100417. [PMID: 39045234 PMCID: PMC11263507 DOI: 10.1016/j.ahjo.2024.100417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 06/20/2024] [Indexed: 07/25/2024]
Abstract
An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets.
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Affiliation(s)
- Enrui Xie
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Department of Infectious Disease, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaotao Shen
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore
- Department of Genetics, Stanford University, California, USA
| | - Yee Hui Yeo
- Department of Genetics, Stanford University, California, USA
| | - Zixuan Xing
- Department of Infectious Disease, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Joseph E. Ebinger
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Yixuan Duan
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yue Zhang
- Department of Infectious Disease, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- The Eighth Hospital of Xi'an City, Xi'an Jiaotong University, Xi'an, China
| | - Susan Cheng
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, USA
| | - Fanpu Ji
- Department of Infectious Disease, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Shaanxi Provincial Clinical Medical Research Center of Infectious Diseases, Xi'an, China
| | - Jie Deng
- Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Yang Y, Zhao M, Kuang Q, You F, Jiang Y. A comprehensive review of phytochemicals targeting macrophages for the regulation of colorectal cancer progression. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 128:155451. [PMID: 38513378 DOI: 10.1016/j.phymed.2024.155451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 01/19/2024] [Accepted: 02/11/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Phytochemicals are natural compounds derived from plants, and are now at the forefront of anti-cancer research. Macrophage immunotherapy plays a crucial role in the treatment of colorectal cancer (CRC). In the context of colorectal cancer, which remains highly prevalent and difficult to treat, it is of research value to explore the potential mechanisms and efficacy of phytochemicals targeting macrophages for CRC treatment. PURPOSE The aim of this study was to gain insight into the role of phytochemical-macrophage interactions in regulating CRC and to provide a theoretical basis for the development of new therapeutic strategies in the future. STUDY DESIGN This review discusses the potential immune mechanisms of phytochemicals for the treatment of CRC by summarizing research of phytochemicals targeting macrophages. METHODS We reviewed the PubMed, EMBASE, Web of Science and CNKI databases from their initial establishment to July 2023 to classify and summaries phytochemicals according to their mechanism of action in targeting macrophages. RESULTS The results of the literature review suggest that phytochemicals interfere with CRC development by affecting macrophages through four main mechanisms. Firstly, they modulate the production of cytotoxic substances, such as NO and ROS, by macrophages to exert anticancer effects. Secondly, phytochemicals polarize macrophages towards the M1 phenotype, inhibit M2 polarisation and enhance the anti-tumour immune responses. Thirdly, they enhance the secretion of macrophage-derived cytokines and alter the tumour microenvironment, thereby inhibiting tumor growth. Finally, they activate the immune response by targeting macrophages, triggering the recruitment of other immune cells, thereby enhancing the immune killing effect and exerting anti-tumor effects. These findings highlight phytochemicals as potential therapeutic strategies to intervene in colorectal cancer development by modulating macrophage activity, providing a strong theoretical basis for future clinical applications. CONCLUSION Phytochemicals exhibit potential anti-tumour effects by modulating macrophage activity and intervening in the colorectal cancer microenvironment by multiple mechanisms.
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Affiliation(s)
- Yi Yang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, PR China
| | - Maoyuan Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, PR China
| | - Qixuan Kuang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, PR China
| | - Fengming You
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, PR China; Cancer Institute, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610075, PR China.
| | - Yifang Jiang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province 610072, PR China.
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10
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Fu S, Song X. The clinical and immunological features of alopecia areata following SARS-CoV-2 infection or COVID-19 vaccines. Expert Opin Ther Targets 2024; 28:273-282. [PMID: 38646688 DOI: 10.1080/14728222.2024.2344696] [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: 12/04/2023] [Accepted: 04/15/2024] [Indexed: 04/23/2024]
Abstract
INTRODUCTION Alopecia areata (AA) is an autoimmune disease induced by viral infection or vaccination. With the increased incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the incidence of AA has also increased. Recently the incidence was found to be 7.8% from a previously reported rate of 2.1%. The physical and psychological damage caused by AA could seriously affect patients' lives, while AA is a challenging dermatological disease owing to its complex pathogenesis. AREAS COVERED This paper presents a comprehensive review of the prevalence, pathogenesis and potential therapeutic targets for AA after infection with SARS-CoV-2 or SARS-CoV-2 vaccine. EXPERT OPINION The treatment of AA remains challenging because of the complexity of its pathogenesis. For patients with AA after SARS-CoV-2 infection or vaccination, the use of sex hormones and alternative regenerative therapies may be actively considered in addition to conventional treatments. For preexisting disease, therapeutic agents should be adjusted to the patient's specific condition.
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Affiliation(s)
- Shiqi Fu
- The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, China
| | - Xiuzu Song
- Department of Dermatology, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital, Hangzhou, China
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11
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Chakraborty C, Bhattacharya M, Lee SS. Regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses: A comprehensive review. Rev Med Virol 2024; 34:e2526. [PMID: 38446531 DOI: 10.1002/rmv.2526] [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: 01/16/2024] [Revised: 02/11/2024] [Accepted: 02/22/2024] [Indexed: 03/07/2024]
Abstract
miRNAs are single-stranded ncRNAs that act as regulators of different human body processes. Several miRNAs have been noted to control the human immune and inflammatory response during severe acute respiratory infection syndrome (SARS-CoV-2) infection. Similarly, many miRNAs were upregulated and downregulated during different respiratory virus infections. Here, an attempt has been made to capture the regulatory role of miRNAs in the human immune and inflammatory response during the infection of SARS-CoV-2 and other respiratory viruses. Firstly, the role of miRNAs has been depicted in the human immune and inflammatory response during the infection of SARS-CoV-2. In this direction, several significant points have been discussed about SARS-CoV-2 infection, such as the role of miRNAs in human innate immune response; miRNAs and its regulation of granulocytes; the role of miRNAs in macrophage activation and polarisation; miRNAs and neutrophil extracellular trap formation; miRNA-related inflammatory response; and miRNAs association in adaptive immunity. Secondly, the miRNAs landscape has been depicted during human respiratory virus infections such as human coronavirus, respiratory syncytial virus, influenza virus, rhinovirus, and human metapneumovirus. The article will provide more understanding of the miRNA-controlled mechanism of the immune and inflammatory response during COVID-19, which will help more therapeutics discoveries to fight against the future pandemic.
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Affiliation(s)
- Chiranjib Chakraborty
- Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal, India
| | | | - Sang-Soo Lee
- Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Gangwon-do, Republic of Korea
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12
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Pastukhova E, Ghazawi FM. New-onset of pemphigus following COVID-19 infection: A case report. SAGE Open Med Case Rep 2024; 12:2050313X241231423. [PMID: 38371950 PMCID: PMC10874115 DOI: 10.1177/2050313x241231423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/11/2023] [Indexed: 02/20/2024] Open
Abstract
COVID-19 has been implicated in various cutaneous autoimmune diseases. Pemphigus is a group of autoimmune blistering diseases that target the desmosomal complexes. Pemphigus triggered by COVID-19 has been seldom reported in the literature and remains both a diagnostic and therapeutic challenge. We report a case of COVID-19-induced pemphigus that responded well to prednisone and mycophenolate mofetil after 9 months from initial presentation. On histologic examination, both intercellular and basement membrane staining were noted. Indirect immunofluorescence staining was positive against the intercellular cement of the stratified epithelium from monkey esophagus. We hypothesize that COVID-19 stimulated the release of multiple pemphigus antigens, which resulted in the unusual histologic pattern reported in the present case. Although malignancy should be suspected when features of paraneoplastic pemphigus, such as basement membrane staining on direct immunofluorescence, are noted, it may also be a histologic pattern of pemphigus secondary to COVID-19 that clinicians may consider.
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Affiliation(s)
- Elena Pastukhova
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Feras M Ghazawi
- Division of Dermatology, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
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13
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Yang D, Chan JFW, Yoon C, Luk TY, Shuai H, Hou Y, Huang X, Hu B, Chai Y, Yuen TTT, Liu Y, Zhu T, Liu H, Shi J, Wang Y, He Y, Sit KY, Au WK, Zhang AJ, Yuan S, Zhang BZ, Huang YW, Chu H. Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways. J Med Virol 2024; 96:e29472. [PMID: 38373201 DOI: 10.1002/jmv.29472] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/22/2024] [Accepted: 01/28/2024] [Indexed: 02/21/2024]
Abstract
Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNβ treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.
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Affiliation(s)
- Dong Yang
- Xianghu Laboratory, Hangzhou, Zhejiang, China
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jasper Fuk-Woo Chan
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
- Academician Workstation of Hainan Province, Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, Hainan Medical University, Haikou, Hainan, China
- The University of Hong Kong, Hong Kong, China
- Department of Microbiology, Queen Mary Hospital, Hong Kong, China
- Guangzhou Laboratory, Guangdong Province, China
| | - Chaemin Yoon
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tsz-Yat Luk
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Huiping Shuai
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yuxin Hou
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Xiner Huang
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Bingjie Hu
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yue Chai
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Terrence Tsz-Tai Yuen
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yuanchen Liu
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tianrenzheng Zhu
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Huan Liu
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Jialu Shi
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yang Wang
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yixin He
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ko-Yung Sit
- Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Wing-Kuk Au
- Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Anna Jinxia Zhang
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
| | - Shuofeng Yuan
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
| | - Bao-Zhong Zhang
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China
| | | | - Hin Chu
- State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, School of Clinical Medicine, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
- Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong, China
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14
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Gan J, Wu J, Zhang H, Liu D, Li W. Immunotherapy against lung cancer does not need to compromise the outcomes of COVID-19. MedComm (Beijing) 2024; 5:e451. [PMID: 38163089 PMCID: PMC10757045 DOI: 10.1002/mco2.451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/23/2023] [Accepted: 11/24/2023] [Indexed: 01/03/2024] Open
Affiliation(s)
- Jiadi Gan
- Department of Respiratory and Critical Care MedicineInstitute of Respiratory HealthCenter of Precision MedicineWest China HospitalSichuan UniversityChengduSichuan ProvinceChina
| | - Jiaxuan Wu
- Department of Respiratory and Critical Care MedicineInstitute of Respiratory HealthCenter of Precision MedicineWest China HospitalSichuan UniversityChengduSichuan ProvinceChina
| | - Huohuo Zhang
- Department of Respiratory and Critical Care MedicineInstitute of Respiratory HealthCenter of Precision MedicineWest China HospitalSichuan UniversityChengduSichuan ProvinceChina
| | - Dan Liu
- Department of Respiratory and Critical Care MedicineInstitute of Respiratory HealthCenter of Precision MedicineWest China HospitalSichuan UniversityChengduSichuan ProvinceChina
| | - Weimin Li
- Department of Respiratory and Critical Care MedicineInstitute of Respiratory HealthCenter of Precision MedicineWest China HospitalSichuan UniversityChengduSichuan ProvinceChina
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15
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Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. JOURNAL OF INTEGRATIVE MEDICINE 2023; 21:413-422. [PMID: 37652781 DOI: 10.1016/j.joim.2023.08.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 04/30/2023] [Indexed: 09/02/2023]
Abstract
Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.
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Affiliation(s)
- Mei Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Rui Zheng
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton L8S 4K1, Canada
| | - Wen-Jing Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
| | - Jun-Ling Hou
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Yu-Lei Yang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
| | - Hong-Cai Shang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.
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16
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Li QY, An ZY, Pan ZH, Wang ZZ, Wang YR, Zhang XG, Shen N. Severe/critical COVID-19 early warning system based on machine learning algorithms using novel imaging scores. World J Clin Cases 2023; 11:2716-2728. [PMID: 37214568 PMCID: PMC10198108 DOI: 10.12998/wjcc.v11.i12.2716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 02/12/2023] [Accepted: 03/17/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Early identification of severe/critical coronavirus disease 2019 (COVID-19) is crucial for timely treatment and intervention. Chest computed tomography (CT) score has been shown to be a significant factor in the diagnosis and treatment of pneumonia, however, there is currently a lack of effective early warning systems for severe/critical COVID-19 based on dynamic CT evolution.
AIM To develop a severe/critical COVID-19 prediction model using a combination of imaging scores, clinical features, and biomarker levels.
METHODS This study used an improved scoring system to extract and describe the chest CT characteristics of COVID-19 patients. The study also took into consideration the general clinical indicators such as dyspnea, oxygen saturation, alternative lengthening of telomeres (ALT), and androgen suppression treatment (AST), which are commonly associated with severe/critical COVID-19 cases. The study employed lasso regression to evaluate and rank the significance of different disease characteristics.
RESULTS The results showed that blood oxygen saturation, ALT, IL-6/IL-10, combined score, ground glass opacity score, age, crazy paving mode score, qsofa, AST, and overall lung involvement score were key factors in predicting severe/critical COVID-19 cases. The study established a COVID-19 severe/critical early warning system using various machine learning algorithms, including XGBClassifier, Logistic Regression, MLPClassifier, RandomForestClassifier, and AdaBoost Classifier. The study concluded that the prediction model based on the improved CT score and machine learning algorithms is a feasible method for early detection of severe/critical COVID-19 evolution.
CONCLUSION The findings of this study suggest that a prediction model based on improved CT scores and machine learning algorithms is effective in detecting the early warning signals of severe/critical COVID-19.
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Affiliation(s)
- Qiu-Yu Li
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Zhuo-Yu An
- Department of Education, Peking University People’s Hospital, Beijing 100044, China
| | - Zi-Han Pan
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
| | - Zi-Zhen Wang
- Department of Education, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yi-Ren Wang
- Department of Education, Peking University People’s Hospital, Beijing 100044, China
| | - Xi-Gong Zhang
- Department of Education, Beijing Jishuitan Hospital, Beijing 100096, China
| | - Ning Shen
- Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
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17
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Qin T, Shen B, Li E, Jin S, Luo R, Zhang Y, Qi J, Deng X, Shi Z, Wang T, Zhou Y, Gao Y. MHC class I links with severe pathogenicity in C57BL/6N mice infected with SARS-CoV-2/BMA8. Virol J 2023; 20:75. [PMID: 37081549 PMCID: PMC10116088 DOI: 10.1186/s12985-023-02031-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 04/04/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice. METHODS Whole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8+ T cells. RESULTS Our results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2Kd showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2Kb in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2Kb inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8+ T cells caused by SARS-CoV-2/BMA8 infection. CONCLUSIONS Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread.
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Affiliation(s)
- Tian Qin
- School of life sciences, Northeast Normal University, Changchun, 130024, China
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Beilei Shen
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Entao Li
- Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China
| | - Song Jin
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
- College of life sciences, Shandong Normal University, Jinan, 250014, China
| | - Rongbo Luo
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Yiming Zhang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Jing Qi
- School of life sciences, Northeast Normal University, Changchun, 130024, China
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Xiuwen Deng
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
- College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Zhuangzhuang Shi
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130033, China
| | - Tiecheng Wang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China
| | - Yifa Zhou
- School of life sciences, Northeast Normal University, Changchun, 130024, China.
| | - Yuwei Gao
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
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18
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Pastukhova E, Ghazawi FM. Eruptive halo nevi and new-onset vitiligo post-COVID-19 infection. JAAD Case Rep 2023; 34:43-44. [PMID: 36816762 PMCID: PMC9927811 DOI: 10.1016/j.jdcr.2023.01.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/19/2023] [Indexed: 02/16/2023] Open
Affiliation(s)
- Elena Pastukhova
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Feras M Ghazawi
- Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.,Division of Dermatology, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada
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19
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Marie-Eve B, Elsa B, Josianne C, Yasmine K, Claude-Emilie J, Camille C, Dorothée DS, Sylvie G. Mediators of inflammation at the maternal-fetal interface are altered by SARS-CoV-2 infection and pandemic stress. Am J Reprod Immunol 2023; 89:e13679. [PMID: 36680541 DOI: 10.1111/aji.13679] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/18/2022] [Accepted: 01/10/2023] [Indexed: 01/22/2023] Open
Abstract
PROBLEM It is now recognized that SARS-CoV-2 infection and pandemic-related stress impacts maternal health. However, their effects at the maternal-fetal interface are still debated. METHOD OF STUDY We recruited 199 women between March 2020 and July 2021, 79 SARS-CoV-2+ and 120 negative (the latter exposed to pandemic stress only). We also included 40 historic controls (i.e. pre-pandemic uncomplicated pregnancies recruited before March 2020). Placental samples were collected for protein and histological analysis. RESULTS The majority of SARS-CoV-2+ women were multiethnic, had higher pre-pregnancy BMI and elevated preterm birth rate (17%) vs SARS-CoV-2- or historic control. Placental inflammatory profile revealed increased IL-1Ra and CRP, independently of SARS-CoV-2 status, whilst MCP-1, IL-6 and IFNγ were elevated in the negative, but pandemic stress-exposed, group. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Furthermore, we observed elevated immune cells (CD45+) in placentas from SARS-CoV-2+ and negative pregnancies vs historic controls, even when individuals with pregnancy complications were excluded. CONCLUSIONS Placental inflammatory profiles differed between SARS-CoV-2 statuses, namely exposed to pandemic stress +/- SARS-CoV-2 infection. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection on placental health.
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Affiliation(s)
- Brien Marie-Eve
- Ste-Justine Hospital Research Center, Montreal, Quebec, Canada
| | - Bernier Elsa
- Ste-Justine Hospital Research Center, Montreal, Quebec, Canada
- Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Quebec, Canada
| | - Clavel Josianne
- Ste-Justine Hospital Research Center, Montreal, Quebec, Canada
| | - Kebiche Yasmine
- Ste-Justine Hospital Research Center, Montreal, Quebec, Canada
| | - Jacob Claude-Emilie
- Department of Obstetrics and Gynecology, Universite de Montreal, Quebec, Canada
- Centre hospitalier de l'Université de Montréal (CHUM), Quebec, Canada
| | - Couture Camille
- Ste-Justine Hospital Research Center, Montreal, Quebec, Canada
- Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Quebec, Canada
| | - Dal Soglio Dorothée
- Department of Pathology and Cell Biology, Universite de Montréal, Montreal, Quebec, Canada
| | - Girard Sylvie
- Department of Microbiology, Infectiology and Immunology, Universite de Montreal, Quebec, Canada
- Department of Obstetrics and Gynecology, Universite de Montreal, Quebec, Canada
- Department of Obstetrics & Gynecology, Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
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20
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Sharma SB, Melvin WJ, Audu CO, Bame M, Rhoads N, Wu W, Kanthi Y, Knight JS, Adili R, Holinstat MA, Wakefield TW, Henke PK, Moore BB, Gallagher KA, Obi AT. The histone methyltransferase MLL1/KMT2A in monocytes drives coronavirus-associated coagulopathy and inflammation. Blood 2023; 141:725-742. [PMID: 36493338 PMCID: PMC9743412 DOI: 10.1182/blood.2022015917] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 11/15/2022] [Accepted: 11/15/2022] [Indexed: 12/13/2022] Open
Abstract
Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, "coagulopathy-related factors") in noninfected and infected cells. We show that MLL1 concurrently promotes the expression of the proinflammatory cytokines while suppressing the expression of interferon alfa (IFN-α), a well-known inducer of TF and PLAUR. Using in vitro models, we identify MLL1-dependent NF-κB/RelA-mediated transcription of these coagulation-related factors and identify a context-dependent, MLL1-independent role for RelA in the expression of these factors in vivo. As functional correlates for these findings, we demonstrate that the inflammatory, procoagulant, and profibrinolytic phenotypes seen in vivo after coronavirus infection were MLL1-dependent despite blunted Ifna induction in MO/Mφs. Finally, in an analysis of SARS-CoV-2 positive human samples, we identify differential upregulation of MLL1 and coagulopathy-related factor expression and activity in CD14+ MO/Mφs relative to noninfected and healthy controls. We also observed elevated plasma PLAU and TF activity in COVID-positive samples. Collectively, these findings highlight an important role for MO/Mφ MLL1 in promoting CAC and inflammation.
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Affiliation(s)
- Sriganesh B. Sharma
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - William J. Melvin
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Christopher O. Audu
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Monica Bame
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI
| | - Nicole Rhoads
- Department of Pharmacology, University of Michigan, Ann Arbor, MI
| | - Weisheng Wu
- Bioinformatics Core, Biomedical Research Core Facilities, University of Michigan, Ann Arbor, MI
| | - Yogendra Kanthi
- Laboratory of Vascular Thrombosis & Inflammation, National Heart, Lung, and Blood Institute, Bethesda, MD
| | - Jason S. Knight
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Reheman Adili
- Department of Pharmacology, University of Michigan, Ann Arbor, MI
| | - Michael A. Holinstat
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Department of Pharmacology, University of Michigan, Ann Arbor, MI
| | - Thomas W. Wakefield
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Peter K. Henke
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
| | - Bethany B. Moore
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI
| | - Katherine A. Gallagher
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI
| | - Andrea T. Obi
- Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
- Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI
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21
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Pastukhova E, Li HOY, Brandts-Longtin O, Kirchhof MG. Alopecia Areata as a Sequela of COVID-19 Vaccination: A Systematic Review. J Cutan Med Surg 2023; 27:64-65. [PMID: 36408862 DOI: 10.1177/12034754221138249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Elena Pastukhova
- 6363 Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Heidi Oi-Yee Li
- 12365 Division of Dermatology, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada
| | | | - Mark G Kirchhof
- 6363 Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.,12365 Division of Dermatology, University of Ottawa, and The Ottawa Hospital, Ottawa, Ontario, Canada
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22
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Dai W, Zhong A, Qiao Q, Wu J, Li W, Wu Q, Zhou H, Qin S, Jiang W, Zhang J, Xia X. Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity. Virol J 2022; 19:192. [DOI: 10.1186/s12985-022-01926-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 11/14/2022] [Indexed: 11/21/2022] Open
Abstract
Abstract
Background
Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated.
Methods
The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients.
Results
In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases.
Conclusion
A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.
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23
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Role of Innate and Adaptive Cytokines in the Survival of COVID-19 Patients. Int J Mol Sci 2022; 23:ijms231810344. [PMID: 36142255 PMCID: PMC9499609 DOI: 10.3390/ijms231810344] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/02/2022] [Accepted: 09/02/2022] [Indexed: 11/16/2022] Open
Abstract
SARS-CoV-2 is a new coronavirus characterized by a high infection and transmission capacity. A significant number of patients develop inadequate immune responses that produce massive releases of cytokines that compromise their survival. Soluble factors are clinically and pathologically relevant in COVID-19 survival but remain only partially characterized. The objective of this work was to simultaneously study 62 circulating soluble factors, including innate and adaptive cytokines and their soluble receptors, chemokines and growth and wound-healing/repair factors, in severe COVID-19 patients who survived compared to those with fatal outcomes. Serum samples were obtained from 286 COVID-19 patients and 40 healthy controls. The 62 circulating soluble factors were quantified using a Luminex Milliplex assay. Results. The patients who survived had decreased levels of the following 30 soluble factors of the 62 studied compared to those with fatal outcomes, therefore, these decreases were observed for cytokines and receptors predominantly produced by the innate immune system—IL-1α, IL-1α, IL-18, IL-15, IL-12p40, IL-6, IL-27, IL-1Ra, IL-1RI, IL-1RII, TNFα, TGFα, IL-10, sRAGE, sTNF-RI and sTNF-RII—for the chemokines IL-8, IP-10, MCP-1, MCP-3, MIG and fractalkine; for the growth factors M-CSF and the soluble receptor sIL2Ra; for the cytokines involved in the adaptive immune system IFNγ, IL-17 and sIL-4R; and for the wound-repair factor FGF2. On the other hand, the patients who survived had elevated levels of the soluble factors TNFβ, sCD40L, MDC, RANTES, G-CSF, GM-CSF, EGF, PDGFAA and PDGFABBB compared to those who died. Conclusions. Increases in the circulating levels of the sCD40L cytokine; MDC and RANTES chemokines; the G-CSF and GM-CSF growth factors, EGF, PDGFAA and PDGFABBB; and tissue-repair factors are strongly associated with survival. By contrast, large increases in IL-15, IL-6, IL-18, IL-27 and IL-10; the sIL-1RI, sIL1RII and sTNF-RII receptors; the MCP3, IL-8, MIG and IP-10 chemokines; the M-CSF and sIL-2Ra growth factors; and the wound-healing factor FGF2 favor fatal outcomes of the disease.
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24
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Wang T, Cao Y, Zhang H, Wang Z, Man CH, Yang Y, Chen L, Xu S, Yan X, Zheng Q, Wang Y. COVID-19 metabolism: Mechanisms and therapeutic targets. MedComm (Beijing) 2022; 3:e157. [PMID: 35958432 PMCID: PMC9363584 DOI: 10.1002/mco2.157] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/26/2022] [Accepted: 06/29/2022] [Indexed: 01/18/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS-CoV-2-induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID-19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS-CoV-2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID-19 metabolism. SARS-CoV-2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS-CoV-2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID-19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS-CoV-2-induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID-19 pandemic.
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Affiliation(s)
- Tianshi Wang
- Shanghai Key Laboratory for Tumor Microenvironment and InflammationDepartment of Biochemistry and Molecular Cell BiologyShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Ying Cao
- State Key Laboratory of Oncogenes and Related GenesShanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Haiyan Zhang
- Bai Jia Obstetrics and Gynecology HospitalShanghaiChina
| | - Zihao Wang
- Fudan University Shanghai Cancer CenterKey Laboratory of Breast Cancer in ShanghaiShanghai Key Laboratory of Radiation OncologyCancer Instituteand The Shanghai Key Laboratory of Medical EpigeneticsInstitutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
- The International Co‐laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghaiChina
| | - Cheuk Him Man
- Division of HematologyDepartment of MedicineUniversity of Hong KongPokfulamHong Kong, China
| | - Yunfan Yang
- Department of Cell BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanChina
| | - Lingchao Chen
- Department of NeurosurgeryHuashan HospitalShanghai Medical CollegeFudan UniversityNational Center for Neurological DisordersShanghai Key Laboratory of Brain Function and Restoration and Neural RegenerationNeurosurgical Institute of Fudan UniversityShanghai Clinical Medical Center of NeurosurgeryShanghaiChina
| | - Shuangnian Xu
- Department of HematologySouthwest HospitalArmy Medical UniversityChongqingChina
| | - Xiaojing Yan
- Department of HematologyThe First Affiliated Hospital of China Medical UniversityShenyangChina
| | - Quan Zheng
- Center for Single‐Cell OmicsSchool of Public HealthShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yi‐Ping Wang
- Fudan University Shanghai Cancer CenterKey Laboratory of Breast Cancer in ShanghaiShanghai Key Laboratory of Radiation OncologyCancer Instituteand The Shanghai Key Laboratory of Medical EpigeneticsInstitutes of Biomedical SciencesShanghai Medical CollegeFudan UniversityShanghaiChina
- Department of OncologyShanghai Medical CollegeFudan UniversityShanghaiChina
- The International Co‐laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghaiChina
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25
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Vaccination, Risk Factors and Outcomes of COVID-19 Infection in Patients with Psoriasis—A Single Centre Real-Life Experience from Eastern Slovakia. Viruses 2022; 14:v14081646. [PMID: 36016267 PMCID: PMC9415362 DOI: 10.3390/v14081646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/22/2022] [Accepted: 07/25/2022] [Indexed: 11/22/2022] Open
Abstract
Coronavirus disease (COVID-19) represents a threat for people with immune-mediated diseases. It seems that patients with psoriasis appear to have a similar SARS-CoV-2 infection rate as the general population. Our study aimed to identify factors associated with contracting COVID-19 and determining the severity of COVID-19 among psoriatic patients in a real practice setting. We conducted a cross-sectional study with 379 respondents. About one-quarter (n = 78; 25.8%) of the respondents who provided information on their COVID-19 (n = 302) status had contracted COVID-19. Most variables tested for their effect on getting COVID-19 proved to be statistically insignificant, except education, age and gender. Our study proved the protective effect of vaccination, especially the third dose, against the COVID-19 outcome. From all the potential variables, we found that non-Roma ethnicity increased the chance of being vaccinated at least once by 2.6-fold. Patients with a longer psoriasis duration had a higher chance of being vaccinated. We consider biological treatment of psoriasis safe during COVID-19. Vaccination of patients was a statistically significant protector against COVID-19. It is important to point out that only three doses of vaccine decreased with statistical significance the chance of getting the illness. Our findings should be confirmed on larger samples in further studies.
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26
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Yang D, Li H, Chen Y, Ren W, Dong M, Li C, Jiao Q. Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19. Front Med (Lausanne) 2022; 9:951115. [PMID: 35957855 PMCID: PMC9357915 DOI: 10.3389/fmed.2022.951115] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.
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Affiliation(s)
- Dinglong Yang
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Hetong Li
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Yujing Chen
- School of Public Health, Xi'an Jiaotong University, Xi'an, China
| | - Weiping Ren
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Mingjie Dong
- Second Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Chunjiang Li
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Qiang Jiao
- Department of Orthopedics, The Second Hospital of Shanxi Medical University, Taiyuan, China
- *Correspondence: Qiang Jiao
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27
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Chen NY, Liu ZH, Kao SW, Lin HS, Lee IK, Zheng JY, Wang SW, Hsiao YH, Lin HC, Wu TS. Changes in Interferon-Gamma Release Assay Readout after COVID-19 Vaccination: A Prospective Cohort Study. Int J Infect Dis 2022; 122:537-542. [PMID: 35788418 PMCID: PMC9247115 DOI: 10.1016/j.ijid.2022.06.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 06/14/2022] [Accepted: 06/27/2022] [Indexed: 11/01/2022] Open
Abstract
OBJECTIVES Interferon-gamma release assays (IGRAs) are widely used in public health practice to diagnose latent tuberculosis. During the coronavirus disease (COVID-19) pandemic and rollout of COVID-19 vaccination, it has remained unclear whether COVID-19 vaccines interfere with IGRA readouts. METHODS We prospectively recruited healthcare workers during their annual occupational health examinations in 2021. Baseline IGRA readouts were compared with follow-up data after the participants had received two doses of COVID-19 vaccination. RESULTS A total of 134 baseline IGRA-negative cases (92 with ChAdOx1 vaccine, 27 with mRNA-1273 vaccine, and 15 with heterologous vaccination) and seven baseline IGRA-positive cases were analysed. Among the baseline IGRA-negative cases, there were decreased interferon-γ concentrations over the Nil (p = 0.005) and increased Mitogen-Nil (p < 0.001) values post-vaccination. For TB2-Nil value, there was a similar trend (p = 0.057) of increase observed. Compared with the 0.35 IU/mL threshold, the baseline and follow-up readout differences were less than |±0.10| IU/mL over the TB1-Nil and TB2-Nil values in >90% baseline IGRA-negative cases. No significant readout difference was observed among baseline IGRA-positive cases. CONCLUSIONS COVID-19 vaccination did not change IGRA interpretation in most cases. Cases showing conversion/borderline IGRA readouts should be given special consideration.
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Affiliation(s)
- Nan-Yu Chen
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taiwan
| | - Zhuo-Hao Liu
- Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Branch, Taiwan
| | - Shu-Wei Kao
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taiwan
| | - Huang-Shen Lin
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Chiayi Branch, Taiwan
| | - Ing-Kit Lee
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Taiwan
| | - Jun-Yuan Zheng
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Keelung Branch, Taiwan
| | - Ssu-Wei Wang
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taiwan
| | - Yu-Hsiang Hsiao
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taiwan
| | - Hui-Chin Lin
- Department of Nursing, Chang Gung Memorial Hospital Linkou Branch, Taiwan
| | - Ting-Shu Wu
- Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University College of Medicine, Taiwan.
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28
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Makaremi S, Asgarzadeh A, Kianfar H, Mohammadnia A, Asghariazar V, Safarzadeh E. The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19. Inflamm Res 2022; 71:923-947. [PMID: 35751653 PMCID: PMC9243884 DOI: 10.1007/s00011-022-01596-w] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/29/2022] [Indexed: 12/12/2022] Open
Abstract
A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.
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Affiliation(s)
- Shima Makaremi
- School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ali Asgarzadeh
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hamed Kianfar
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Alireza Mohammadnia
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Vahid Asghariazar
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran. .,Department of Microbiology, Parasitology and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
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29
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Babajani A, Moeinabadi-Bidgoli K, Niknejad F, Rismanchi H, Shafiee S, Shariatzadeh S, Jamshidi E, Farjoo MH, Niknejad H. Human placenta-derived amniotic epithelial cells as a new therapeutic hope for COVID-19-associated acute respiratory distress syndrome (ARDS) and systemic inflammation. Stem Cell Res Ther 2022; 13:126. [PMID: 35337387 PMCID: PMC8949831 DOI: 10.1186/s13287-022-02794-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 02/25/2022] [Indexed: 02/07/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has become in the spotlight regarding the serious early and late complications, including acute respiratory distress syndrome (ARDS), systemic inflammation, multi-organ failure and death. Although many preventive and therapeutic approaches have been suggested for ameliorating complications of COVID-19, emerging new resistant viral variants has called the efficacy of current therapeutic approaches into question. Besides, recent reports on the late and chronic complications of COVID-19, including organ fibrosis, emphasize a need for a multi-aspect therapeutic method that could control various COVID-19 consequences. Human amniotic epithelial cells (hAECs), a group of placenta-derived amniotic membrane resident stem cells, possess considerable therapeutic features that bring them up as a proposed therapeutic option for COVID-19. These cells display immunomodulatory effects in different organs that could reduce the adverse consequences of immune system hyper-reaction against SARS-CoV-2. Besides, hAECs would participate in alveolar fluid clearance, renin-angiotensin-aldosterone system regulation, and regeneration of damaged organs. hAECs could also prevent thrombotic events, which is a serious complication of COVID-19. This review focuses on the proposed early and late therapeutic mechanisms of hAECs and their exosomes to the injured organs. It also discusses the possible application of preconditioned and genetically modified hAECs as well as their promising role as a drug delivery system in COVID-19. Moreover, the recent advances in the pre-clinical and clinical application of hAECs and their exosomes as an optimistic therapeutic hope in COVID-19 have been reviewed.
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Affiliation(s)
- Amirhesam Babajani
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kasra Moeinabadi-Bidgoli
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farnaz Niknejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Rismanchi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepehr Shafiee
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Siavash Shariatzadeh
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elham Jamshidi
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hadi Farjoo
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hassan Niknejad
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. PLoS Genet 2022; 18:e1010042. [PMID: 35239653 PMCID: PMC8893330 DOI: 10.1371/journal.pgen.1010042] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 01/18/2022] [Indexed: 12/30/2022] Open
Abstract
In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.
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Won T, Gilotra NA, Wood MK, Hughes DM, Talor MV, Lovell J, Milstone AM, Steenbergen C, Čiháková D. Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination. Front Immunol 2022; 13:851620. [PMID: 35251049 PMCID: PMC8894592 DOI: 10.3389/fimmu.2022.851620] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 01/31/2022] [Indexed: 12/25/2022] Open
Abstract
Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality. His endomyocardial biopsy revealed diffuse CD68+ cell infiltration. We characterized the immune profile of the patient using multiplex cytokine assay and flow cytometry analysis. Sex-matched vaccinated individuals and healthy individuals were used as controls. IL-18 and IL-27, Th1-type cytokines, were highly increased in the patient with COVID-19 vaccine-related myopericarditis compared with vaccinated controls who experienced no cardiac complications. In the patient, circulating NK cells and T cells showed an activated phenotype and mRNA profile, and monocytes expressed increased levels of IL-18 and its upstream NLRP3 inflammasome. We found that recombinant IL-18 administration into mice caused mild cardiac dysfunction and activation of NK cells and T cells in the hearts, similar to the findings in the patient with myopericarditis after COVID-19 mRNA vaccination. Collectively, myopericarditis following COVID-19 mRNA vaccination may be associated with increased IL-18-mediated immune responses and cardiotoxicity.
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Affiliation(s)
- Taejoon Won
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Nisha Aggarwal Gilotra
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Megan Kay Wood
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
| | - David Matthew Hughes
- Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, United States
| | - Monica Vladut Talor
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Jana Lovell
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Aaron Michael Milstone
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Charles Steenbergen
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Daniela Čiháková
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States
- *Correspondence: Daniela Čiháková, ; orcid.org/0000-0002-8713-2860
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32
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Saheb Sharif-Askari F, Goel S, Saheb Sharif-Askari N, Hafezi S, Al Heialy S, Hachim MY, Hachim IY, Mahboub B, Salameh L, Abdelrazig M, Elzain EI, Al-Muhsen S, Al-Hajjaj MS, Ratemi E, Hamid Q, Halwani R. Asthma Associated Cytokines Regulate the Expression of SARS-CoV-2 Receptor ACE2 in the Lung Tissue of Asthmatic Patients. Front Immunol 2022; 12:796094. [PMID: 35111161 PMCID: PMC8801531 DOI: 10.3389/fimmu.2021.796094] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/22/2021] [Indexed: 01/10/2023] Open
Abstract
It is still controversial whether chronic lung inflammation increases the risk for COVID-19. One of the risk factors for acquiring COVID-19 is the level of expression of SARS-CoV-2 entry receptors, ACE2 and TMPRSS2, in lung tissue. It is, however, not clear how lung tissue inflammation affects expression levels of these receptors. We hence aimed to determine the level of SARS-CoV-2 receptors in lung tissue of asthmatic relative to age, gender, and asthma severity, and to investigate the factors regulating that. Therefore, gene expression data sets of well-known asthmatic cohorts (SARP and U-BIOPRED) were used to evaluate the association of ACE2 and TMPRSS2 with age, gender of the asthmatic patients, and also the type of the underlying lung tissue inflammatory cytokines. Notably, ACE2 and to less extent TMPRSS2 expression were upregulated in the lung tissue of asthmatics compared to healthy controls. Although a differential expression of ACE2, but not TMPRSS2 was observed relative to age within the moderate and severe asthma groups, our data suggest that age may not be a key regulatory factor of its expression. The type of tissue inflammation, however, associated significantly with ACE2 and TMPRSS2 expression levels following adjusting with age, gender and oral corticosteroids use of the patient. Type I cytokine (IFN-γ), IL-8, and IL-19 were associated with increased expression, while Type II cytokines (IL-4 and IL-13) with lower expression of ACE2 in lung tissue (airway epithelium and/or lung biopsies) of moderate and severe asthmatic patients. Of note, IL-19 was associated with ACE2 expression while IL-17 was associated with TMPRSS2 expression in sputum of asthmatic subjects. In vitro treatment of bronchial fibroblasts with IL-17 and IL-19 cytokines confirmed the regulatory effect of these cytokines on SARS-CoV-2 entry receptors. Our results suggest that the type of inflammation may regulate ACE2 and TMPRSS2 expression in the lung tissue of asthmatics and may hence affect susceptibility to SARS-CoV-2 infection.
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Affiliation(s)
- Fatemeh Saheb Sharif-Askari
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Swati Goel
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Narjes Saheb Sharif-Askari
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Shirin Hafezi
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Saba Al Heialy
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.,Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada
| | - Mahmood Yaseen Hachim
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Ibrahim Yaseen Hachim
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Bassam Mahboub
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | - Laila Salameh
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | - Mawada Abdelrazig
- Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates
| | | | - Saleh Al-Muhsen
- Immunology Research Lab, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.,Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed S Al-Hajjaj
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Elaref Ratemi
- Jubail-Industrial College, Department of Chemical and Process Engineering Technology, Jubail-Industrial City, Saudi Arabia
| | - Qutayba Hamid
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada.,Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Rabih Halwani
- Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.,Prince Abdullah Ben Khaled Celiac Disease Chair, department of pediatrics, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia
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Geronikolou SA, Takan I, Pavlopoulou A, Mantzourani M, Chrousos GP. Thrombocytopenia in COVID‑19 and vaccine‑induced thrombotic thrombocytopenia. Int J Mol Med 2022; 49:35. [PMID: 35059730 PMCID: PMC8815408 DOI: 10.3892/ijmm.2022.5090] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 12/28/2021] [Indexed: 12/16/2022] Open
Abstract
The highly heterogeneous symptomatology and unpredictable progress of COVID-19 triggered unprecedented intensive biomedical research and a number of clinical research projects. Although the pathophysiology of the disease is being progressively clarified, its complexity remains vast. Moreover, some extremely infrequent cases of thrombotic thrombocytopenia following vaccination against SARS-CoV-2 infection have been observed. The present study aimed to map the signaling pathways of thrombocytopenia implicated in COVID-19, as well as in vaccine-induced thrombotic thrombocytopenia (VITT). The biomedical literature database, MEDLINE/PubMed, was thoroughly searched using artificial intelligence techniques for the semantic relations among the top 50 similar words (>0.9) implicated in COVID-19-mediated human infection or VITT. Additionally, STRING, a database of primary and predicted associations among genes and proteins (collected from diverse resources, such as documented pathway knowledge, high-throughput experimental studies, cross-species extrapolated information, automated text mining results, computationally predicted interactions, etc.), was employed, with the confidence threshold set at 0.7. In addition, two interactomes were constructed: i) A network including 119 and 56 nodes relevant to COVID-19 and thrombocytopenia, respectively; and ii) a second network containing 60 nodes relevant to VITT. Although thrombocytopenia is a dominant morbidity in both entities, three nodes were observed that corresponded to genes (AURKA, CD46 and CD19) expressed only in VITT, whilst ADAM10, CDC20, SHC1 and STXBP2 are silenced in VITT, but are commonly expressed in both COVID-19 and thrombocytopenia. The calculated average node degree was immense (11.9 in COVID-19 and 6.43 in VITT), illustrating the complexity of COVID-19 and VITT pathologies and confirming the importance of cytokines, as well as of pathways activated following hypoxic events. In addition, PYCARD, NLP3 and P2RX7 are key potential therapeutic targets for all three morbid entities, meriting further research. This interactome was based on wild-type genes, revealing the predisposition of the body to hypoxia-induced thrombosis, leading to the acute COVID-19 phenotype, the 'long-COVID syndrome', and/or VITT. Thus, common nodes appear to be key players in illness prevention, progression and treatment.
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Affiliation(s)
- Styliani A Geronikolou
- Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece
| | - Işil Takan
- Izmir Biomedicine and Genome Center (IBG), 35340 Izmir, Turkey
| | | | - Marina Mantzourani
- First Department of Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece
| | - George P Chrousos
- Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece
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Konrad ER, Soo J, Conroy AL, Namasopo S, Opoka RO, Hawkes MT. Interleukin-18 binding protein in infants and children hospitalized with pneumonia in low-resource settings. Cytokine 2021; 150:155775. [PMID: 34875584 DOI: 10.1016/j.cyto.2021.155775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/14/2021] [Accepted: 11/24/2021] [Indexed: 11/27/2022]
Abstract
Pneumonia is the leading infectious cause of death in children, with especially high mortality in low- and middle-income countries. Interleukin-18 binding protein (IL-18BP) is a natural antagonist of the pro-inflammatory cytokine interleukin-18 and is elevated in numerous autoimmune conditions and infectious diseases. We conducted a prospective cohort study to determine the association between admission IL-18BP levels and clinical severity among children admitted to two hospitals in Uganda for hypoxemic pneumonia. A total of 42 children (median age of 1.2 years) were included. IL-18BP levels were higher in patients with respiratory distress, including chest indrawing (median 15 ng/mL (IQR 9.8-18) versus 4.5 ng/mL (IQR 3.8-11) without chest indrawing, P = 0.0064) and nasal flaring (median 15 ng/mL (IQR 9.7-19) versus 11 ng/mL (IQR 5.4-14) without nasal flaring, P = 0.034). IL-18BP levels were positively correlated with the composite clinical severity score, Pediatric Early Death Index for Africa (PEDIA-e, ρ = 0.46, P = 0.0020). Patients with IL-18BP > 14 ng/mL also had slower recovery times, including time to sit (median 0.69 days (IQR 0.25-1) versus 0.15 days (IQR 0.076-0.36) with IL-18BP < 14 ng/mL, P = 0.036) and time to fever resolution (median 0.63 days (IQR 0.16-2) versus 0.13 days (IQR 0-0.42), P = 0.016). In summary, higher IL-18BP levels were associated with increased disease severity and prolonged recovery times in Ugandan children with pneumonia.
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Affiliation(s)
- Emily R Konrad
- Department of Pediatrics, University of Alberta, Edmonton, Canada
| | - Jeremy Soo
- Department of Pediatrics, University of Alberta, Edmonton, Canada
| | - Andrea L Conroy
- Ryan White Center for Pediatric Infectious Diseases and Global Health, Indiana University School of Medicine, Indianapolis, USA
| | | | - Robert O Opoka
- Department of Paediatrics and Child Health, Mulago Hospital and Makerere University, Kampala, Uganda
| | - Michael T Hawkes
- Department of Pediatrics, University of Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada; Distinguished Researcher, Stollery Science Lab, Canada; Member, Women and Children's Health Research Institute, Canada.
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35
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Koushki K, Salemi M, Miri SM, Arjeini Y, Keshavarz M, Ghaemi A. Role of myeloid-derived suppressor cells in viral respiratory infections; Hints for discovering therapeutic targets for COVID-19. Biomed Pharmacother 2021; 144:112346. [PMID: 34678727 PMCID: PMC8516725 DOI: 10.1016/j.biopha.2021.112346] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/07/2021] [Accepted: 10/13/2021] [Indexed: 02/06/2023] Open
Abstract
The expansion of myeloid-derived suppressor cells (MDSCs), known as heterogeneous population of immature myeloid cells, is enhanced during several pathological conditions such as inflammatory or viral respiratory infections. It seems that the way MDSCs behave in infection depends on the type and the virulence mechanisms of the invader pathogen, the disease stage, and the infection-related pathology. Increasing evidence showing that in correlation with the severity of the disease, MDSCs are accumulated in COVID-19 patients, in particular in those at severe stages of the disease or ICU patients, contributing to pathogenesis of SARS-CoV2 infection. Based on the involved subsets, MDSCs delay the clearance of the virus through inhibiting T-cell proliferation and responses by employing various mechanisms such as inducing the secretion of anti-inflammatory cytokines, inducible nitric oxide synthase (iNOS)-mediated hampering of IFN-γ production, or forcing arginine shortage. While the immunosuppressive characteristic of MDSCs may help to preserve the tissue homeostasis and prevent hyperinflammation at early stages of the infection, hampering of efficient immune responses proved to exert significant pathogenic effects on severe forms of COVID-19, suggesting the targeting of MDSCs as a potential intervention to reactivate T-cell immunity and thereby prevent the infection from developing into severe stages of the disease. This review tried to compile evidence on the roles of different subsets of MDSCs during viral respiratory infections, which is far from being totally understood, and introduce the promising potential of MDSCs for developing novel diagnostic and therapeutic approaches, especially against COVID-19 disease.
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Affiliation(s)
- Khadijeh Koushki
- Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Salemi
- Department of Medical Virology, The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Seyed Mohammad Miri
- Department of Influenza and Other Respiratory Viruses, Pasteur Institute of Iran, Tehran, Iran
| | - Yaser Arjeini
- Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran
| | - Mohsen Keshavarz
- Department of Medical Virology, The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.
| | - Amir Ghaemi
- Department of Influenza and Other Respiratory Viruses, Pasteur Institute of Iran, Tehran, Iran.
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Rossi A, Magri F, Michelini S, Caro G, Di Fraia M, Fortuna MC, Pellacani G, Carlesimo M. Recurrence of alopecia areata after covid-19 vaccination: A report of three cases in Italy. J Cosmet Dermatol 2021; 20:3753-3757. [PMID: 34741583 DOI: 10.1111/jocd.14581] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 10/18/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND Common COVID-19 vaccines side effects are pain at the injection site, muscle pain, fever, headaches, fatigue. Possible immune-related side effects in predisposed individuals have not been established so far. MATERIALS AND METHODS We report three cases of recurrence of alopecia areata (AA) occurred after the first dose of COVID-19 vaccine. RESULTS All patients had previous episodes of AA with total hair regrowth and stable remission during the months preceding the vaccination. Rapid hair loss occurred 2-3 weeks after BNT162b2 mRNA (patient 1) and AZD1222/ChAdOx1 vaccine (patient 2 and 3), with widespread hair loss in two cases and a single patch of the vertex in one case, with typical trichoscopic features of AA. DISCUSSION Both BNT162b2 mRNA and AZD1222/ChAdOx1 vaccines share the same goal of inducing the immune system, with antibodies production and Th1 cells activation with release of pro-inflammatory cytokines. Thus, in patients with pre-existing inflammatory dysregulated pathways, the interaction between the immune system and vaccines may enhance other autoimmune mechanisms. In our cases, we speculate that vaccine may have induced the hair loss focusing on components having a key role in both COVID-19 vaccination and AA pathogenesis. CONCLUSION This report may help to collect new data concerning possible immune-related effects of vaccines. Certainly, only three cases are not sufficient to draw conclusion, thus a large-scale study is necessary. Immune-mediated side effects remain a rare event, thus the benefits of COVID-19 vaccines outweigh the risk of disease flares and we strongly recommend it in all eligible patients with AA.
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Affiliation(s)
- Alfredo Rossi
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Francesca Magri
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Simone Michelini
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Gemma Caro
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marco Di Fraia
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Caterina Fortuna
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Giovanni Pellacani
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Marta Carlesimo
- Dermatologic Unit, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
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Zeng X, Jiang X, Yang L, Pan Y, Li Y. COVID-19 and Cancer: Discovery of Difference in Clinical Immune Indexes. J Immunol Res 2021; 2021:8669098. [PMID: 34712741 PMCID: PMC8546403 DOI: 10.1155/2021/8669098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 08/19/2021] [Accepted: 09/08/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. METHODS This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. RESULTS COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. CONCLUSION Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.
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Affiliation(s)
- Xiaojiao Zeng
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Xianghu Jiang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Liu Yang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yunbao Pan
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
| | - Yirong Li
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China
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Bisgin A, Sanlioglu AD, Eksi YE, Griffith TS, Sanlioglu S. Current Update on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development with a Special Emphasis on Gene Therapy Viral Vector Design and Construction for Vaccination. Hum Gene Ther 2021; 32:541-562. [PMID: 33858231 DOI: 10.1089/hum.2021.052] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease (COVID-19) caused by the novel coronavirus SARS-coronavirus 2 (CoV-2). To combat the devastating spread of SARS-CoV-2, extraordinary efforts from numerous laboratories have focused on the development of effective and safe vaccines. Traditional live-attenuated or inactivated viral vaccines are not recommended for immunocompromised patients as the attenuated virus can still cause disease via phenotypic or genotypic reversion. Subunit vaccines require repeated dosing and adjuvant use to be effective, and DNA vaccines exhibit lower immune responses. mRNA vaccines can be highly unstable under physiological conditions. On the contrary, naturally antigenic viral vectors with well-characterized structure and safety profile serve as among the most effective gene carriers to provoke immune response via heterologous gene transfer. Viral vector-based vaccines induce both an effective cellular immune response and a humoral immune response owing to their natural adjuvant properties via transduction of immune cells. Consequently, viral vectored vaccines carrying the SARS-CoV-2 spike protein have recently been generated and successfully used to activate cytotoxic T cells and develop a neutralizing antibody response. Recent progress in SARS-CoV-2 vaccines, with an emphasis on gene therapy viral vector-based vaccine development, is discussed in this review.
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Affiliation(s)
- Atil Bisgin
- The Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya, Turkey
- Department of Medical Genetics, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Ahter D Sanlioglu
- The Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Yunus Emre Eksi
- The Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya, Turkey
| | - Thomas S Griffith
- The Department of Urology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Salih Sanlioglu
- The Department of Gene and Cell Therapy, Faculty of Medicine, Akdeniz University, Antalya, Turkey
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Charoenkwan P, Chiangjong W, Nantasenamat C, Hasan MM, Manavalan B, Shoombuatong W. StackIL6: a stacking ensemble model for improving the prediction of IL-6 inducing peptides. Brief Bioinform 2021; 22:6271998. [PMID: 33963832 DOI: 10.1093/bib/bbab172] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 03/30/2021] [Accepted: 04/10/2021] [Indexed: 12/13/2022] Open
Abstract
The release of interleukin (IL)-6 is stimulated by antigenic peptides from pathogens as well as by immune cells for activating aggressive inflammation. IL-6 inducing peptides are derived from pathogens and can be used as diagnostic biomarkers for predicting various stages of disease severity as well as being used as IL-6 inhibitors for the suppression of aggressive multi-signaling immune responses. Thus, the accurate identification of IL-6 inducing peptides is of great importance for investigating their mechanism of action as well as for developing diagnostic and immunotherapeutic applications. This study proposes a novel stacking ensemble model (termed StackIL6) for accurately identifying IL-6 inducing peptides. More specifically, StackIL6 was constructed from twelve different feature descriptors derived from three major groups of features (composition-based features, composition-transition-distribution-based features and physicochemical properties-based features) and five popular machine learning algorithms (extremely randomized trees, logistic regression, multi-layer perceptron, support vector machine and random forest). To enhance the utility of baseline models, they were effectively and systematically integrated through a stacking strategy to build the final meta-based model. Extensive benchmarking experiments demonstrated that StackIL6 could achieve significantly better performance than the existing method (IL6PRED) and outperformed its constituent baseline models on both training and independent test datasets, which thereby support its excellent discrimination and generalization abilities. To facilitate easy access to the StackIL6 model, it was established as a freely available web server accessible at http://camt.pythonanywhere.com/StackIL6. It is anticipated that StackIL6 can help to facilitate rapid screening of promising IL-6 inducing peptides for the development of diagnostic and immunotherapeutic applications in the future.
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Affiliation(s)
- Phasit Charoenkwan
- Modern Management and Information Technology, College of Arts, Media and Technology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Wararat Chiangjong
- Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
| | - Chanin Nantasenamat
- Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand
| | - Md Mehedi Hasan
- Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan
| | | | - Watshara Shoombuatong
- Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand
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Wu Z, Zhang Q, Ye G, Zhang H, Heng BC, Fei Y, Zhao B, Zhou J. Structural and physiological changes of the human body upon SARS-CoV-2 infection. J Zhejiang Univ Sci B 2021; 22:310-317. [PMID: 33835765 PMCID: PMC8042530 DOI: 10.1631/jzus.b2000523] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Accepted: 01/03/2021] [Indexed: 12/28/2022]
Abstract
Since December 2019, the novel coronavirus (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread to many countries around the world, developing into a global pandemic with increasing numbers of deaths reported worldwide. To data, although some vaccines have been developed, there are no ideal drugs to treat novel coronavirus pneumonia (coronavirus disease 2019 (COVID-19)). By examining the structure of the coronavirus and briefly describing its possible pathogenesis based on recent autopsy reports conducted by various teams worldwide, this review analyzes the possible structural and functional changes of the human body upon infection with SARS-CoV-2. We observed that the most prominent pathological changes in COVID-19 patients are diffuse alveolar damage (DAD) of the lungs and microthrombus formation, resulting in an imbalance of the ventilation/perfusion ratio and respiratory failure. Although direct evidence of viral infection can also be found in other organs and tissues, the viral load is relatively small. The conclusion that the injuries of the extra-pulmonary organs are directly caused by the virus needs further investigation.
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Affiliation(s)
- Zhonglin Wu
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Zhejiang University-University of Edinburgh Institute, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Qi Zhang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Zhejiang University-University of Edinburgh Institute, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Guo Ye
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Zhejiang University-University of Edinburgh Institute, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Hui Zhang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Zhejiang University-University of Edinburgh Institute, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Boon Chin Heng
- Central Laboratories, School of Stomatology, Peking University, Beijing 100871, China
| | - Yang Fei
- Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Bing Zhao
- Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jing Zhou
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
- Zhejiang University-University of Edinburgh Institute, Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou 310058, China.
- Department of Sports Medicine, Zhejiang University School of Medicine, Hangzhou 310009, China.
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