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Chung J, Pierce J, Franklin C, Olson RM, Morrison AR, Amos-Landgraf J. Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19. Dis Model Mech 2025; 18:dmm052086. [PMID: 40195851 PMCID: PMC12010913 DOI: 10.1242/dmm.052086] [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] [Indexed: 04/09/2025] Open
Abstract
Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.
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Affiliation(s)
- James Chung
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
| | - Julia Pierce
- Vascular Research Laboratory, Providence VA Medical Center, Providence, RI 02908, USA
- Department of Research, Ocean State Research Institute, Inc., Providence, RI 02908-4734, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, RI 02908, USA
| | - Craig Franklin
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
| | - Rachel M. Olson
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
- Laboratory for Infectious Disease Research, University of Missouri, Columbia, MO 65211, USA
| | - Alan R. Morrison
- Vascular Research Laboratory, Providence VA Medical Center, Providence, RI 02908, USA
- Department of Research, Ocean State Research Institute, Inc., Providence, RI 02908-4734, USA
- Department of Internal Medicine, Alpert Medical School of Brown University, Providence, RI 02908, USA
| | - James Amos-Landgraf
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA
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Yattassaye MA, Henna F, Kihunyu AM, Eric NP, Ghaderi M, Ipomai V, Shaikh STBS, Irshad M, Akoto NGO, Rath S, Tigui JG. Multiorgan Failure Post-Abdominal Surgery: A Systematic Review of Trends and Clinical Outcomes.. [DOI: 10.21203/rs.3.rs-6187343/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/10/2025]
Abstract
Abstract
Introduction:
Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening condition, characterized by the failure of two or more organ systems. It often follows a Major Abdominal Surgery (MAS). Even with improved surgical care, it remains a leading cause of ICU related deaths. Its pathophysiology is still not clearly understood and data on management is limited.
Objective
This systematic review aims to analyze trends and clinical outcomes of multiple organ failure following a major abdominal surgery.
Methods
A comprehensive literature search was conducted using SCOPUS, Web of Science and MEDLINE (via PubMed) to identify studies on multiple organ failure following a major abdominal surgery.
Results
The study reviewed 14 articles involving 8,267 patients and found a 19.27% incidence of MODS. The systems mainly affected were the liver, circulatory, coagulation and pulmonary systems. Mortality was 3.5%, influenced by disease severity and organ involvement.
Conclusion
Multiple Organ Dysfunction Syndrome (MODS) remains an important concern following major abdominal surgery. This review shows age, gender, and organ involvement as key factors in its development. Early detection using scoring systems have been found to be crucial for management. However, variability in studies limits generalizability, requiring further research.
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Khan S, Hussain Timraz J, Al Ghamdi NA, Metwali NY, Yaseen FA, Alshaqha AM, Alamri SH, Turkistani H, Dwaima A, Ali Algarni I. COVID-19 and Its Effects on the Hepatobiliary System: A Literature Review. Cureus 2025; 17:e80231. [PMID: 40190856 PMCID: PMC11972666 DOI: 10.7759/cureus.80231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2025] [Indexed: 04/09/2025] Open
Abstract
COVID-19 encompasses a wide clinical spectrum, from mild influenza-like illness to severe pneumonia and systemic complications. There is emerging literature on hepatobiliary involvement in COVID-19, especially elevation in liver enzymes as surrogate markers of liver injury. Angiotensin-converting enzyme 2 receptors within the hepatobiliary system are a portal of entry for SARS-CoV-2, after which injury may be perpetuated through hypoxia and cytokine storms. This literature review covers studies published before 2024 from databases such as PubMed, Google Scholar, Springer, and BMC Library. The keywords used were "COVID-19", "liver", "SARS-CoV-2", "chronic liver disease", and other relevant terms to ensure a wide scope of investigation. The most common liver enzymes elevated among COVID-19 patients include aspartate transaminase, alanine transaminase, and alkaline phosphatase, all of which are associated with the severity of the disease. Chronic liver disease (CLD) and hepatocellular carcinoma (HCC) patients have worse outcomes with increased ICU admission rates and increased mortality. COVID-19 vaccination in CLD and liver transplant recipients is very often associated with suboptimal antibody responses, adding to the risks. SARS-CoV-2 causes liver involvement through direct viral cytopathic effects, immune-mediated injury, and systemic hypoxia. Individuals with CLD are particularly vulnerable to severe illness.
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Affiliation(s)
- Sariya Khan
- General Medicine and Surgery, Batterjee Medical College, Jeddah, SAU
| | | | | | - Nada Y Metwali
- Obstetrics and Gynecology, Batterjee Medical College, Jeddah, SAU
| | - Faten A Yaseen
- Medicine and Surgery, Batterjee Medical College, Jeddah, SAU
| | | | - Sarah H Alamri
- Internal Medicine, Batterjee Medical College, Jeddah, SAU
| | | | - Anas Dwaima
- Internal Medicine, International Medical Center Hospital, Jeddah, SAU
| | - Ibraheem Ali Algarni
- Family Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, SAU
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Vrsaljko N, Radmanic Matotek L, Zidovec-Lepej S, Vince A, Papic N. The Impact of Steatotic Liver Disease on Cytokine and Chemokine Kinetics During Sepsis. Int J Mol Sci 2025; 26:2226. [PMID: 40076848 PMCID: PMC11900930 DOI: 10.3390/ijms26052226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/26/2025] [Accepted: 02/28/2025] [Indexed: 03/14/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been linked with sepsis outcomes. However, the immune mechanisms by which MASLD aggravates sepsis severity are unknown. This prospective cohort study aimed to analyze serum cytokine and chemokine kinetics in patients with MASLD and community-acquired sepsis. Out of the 124 patients, 68 (55%) were diagnosed with MASLD. There were no differences in age, sex, comorbidities, baseline sepsis severity, or etiology between the groups. Serum concentrations of 27 cytokines and chemokines on admission and day 5 of hospitalization were analyzed using a multiplex bead-based assay. Patients with MASLD had significantly higher serum concentrations of IL17A, IL-23, IL-33, CXCL10 and TGF-β1. Different cytokine kinetics were observed; patients with MASLD had a decrease in IL-10, IL-23, CXCL10 and TGF-β1, and an increase in IL-33, CXCL5 and CXCL1 on day 5. In the non-MASLD group, there was a decrease in IFN-γ, IL-6, IL-23 and CCL20, and an increase in CCL11 and CXCL5. While TGF-β1 significantly increased in non-MASLD, in MASLD, it decreased on day 5. Kinetics of TGF- β1 and CCL11 were associated with mortality in patients with MASLD. In conclusion, MASLD is linked with distinct cytokine and chemokine profiles during sepsis.
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Affiliation(s)
- Nina Vrsaljko
- Emergency Infectious Diseases Department, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia;
| | - Leona Radmanic Matotek
- Department for Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia; (L.R.M.); (S.Z.-L.)
| | - Snjezana Zidovec-Lepej
- Department for Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia; (L.R.M.); (S.Z.-L.)
| | - Adriana Vince
- Department for Viral Hepatitis, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia;
| | - Neven Papic
- Department for Viral Hepatitis, University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, 10000 Zagreb, Croatia;
- Department for Infectious Diseases, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
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Li Y, Zou H, Ma L, Hu D, Long H, Lin J, Luo Z, Zhou Y, Liao F, Wang X, Meng Y, Wang W, Li G, Zhang Z. Fuzheng Jiedu decoction alleviates H1N1 virus-induced acute lung injury in mice by suppressing the NLRP3 inflammasome activation. JOURNAL OF ETHNOPHARMACOLOGY 2025; 341:119314. [PMID: 39746408 DOI: 10.1016/j.jep.2024.119314] [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: 06/11/2024] [Revised: 12/28/2024] [Accepted: 12/30/2024] [Indexed: 01/04/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI). AIM OF THE STUDY This research sought to explore the impact and underlying mechanisms of FZJDD on ALI caused by the H1N1 virus in mice. MATERIALS AND METHODS FZJDD was characterized using UHPLC-MS/MS. A mouse model infected with H1N1 virus was used to examine the therapeutic and protective benefits of FZJDD in a living organism, by monitoring body weight fluctuations, lung index, histopathological changes, lung injury scores, and survival rates. Lung tissues underwent haematoxylin-eosin staining, western blotting, qRT-PCR and plaque reduction assay. Blood serum was gathered to assess levels of IL-1β, IL-6, TNF-α through ELISA testing. The impact of FZJDD on the NLRP3 inflammasome was further evaluated in macrophages. RESULTS FZJDD treatment significantly mitigated weight loss, reduced lung index, alleviated histopathological injury, and improved the survival rates in mice with H1N1 virus-induced ALI, demonstrating a protective effect against influenza virus infection. qRT-PCR and Western blot assays revealed that FZJDD treatment ameliorated the hyperinflammatory response caused by the H1N1 virus in lung tissue by suppressing NLRP3 inflammasome activation, without impacting viral replication. In vitro experiments additionally verified that FZJDD treatment can suppress the activation of the NLRP3 inflammasome triggered by the H1N1 virus. CONCLUSION Our findings demonstrate that FZJDD treatment can mitigate ALI caused by H1N1 virus and enhance the survival rate in mice, while it doesn't lower viral titers in the lungs. FZJDD achieves these outcomes by curbing excessive inflammation and blocking the activation of NLRP3 inflammasome.
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Affiliation(s)
- Yuting Li
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Haimei Zou
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Lin Ma
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Dingwen Hu
- State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China
| | - Haishan Long
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Jingnan Lin
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China
| | - Ziqing Luo
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Ye Zhou
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Feng Liao
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Xianyang Wang
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Yu Meng
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China
| | - Wenbiao Wang
- Medical Research Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
| | - Geng Li
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Chinese Medicine Guangdong Laboratory, Guangdong, Hengqin, 519031, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
| | - Zhongde Zhang
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China; Chinese Medicine Guangdong Laboratory, Guangdong, Hengqin, 519031, China; State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
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6
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Shafigh A, Mohammadi-Garebagh A, Shahsavarinia K, Tayebi S, Mostafaei A, Salehi-Pourmehr H, Hajebrahimi S. A systematic review on the correlation between COVID-19 and lower urinary tract symptoms. JOURNAL OF CLINICAL VIROLOGY PLUS 2025; 5:100202. [DOI: 10.1016/j.jcvp.2025.100202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2025] Open
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Ghiasi M, Kheirandish Zarandi P, Dayani A, Salimi A, Shokri E. Potential therapeutic effects and nano-based delivery systems of mesenchymal stem cells and their isolated exosomes to alleviate acute respiratory distress syndrome caused by COVID-19. Regen Ther 2024; 27:319-328. [PMID: 38650667 PMCID: PMC11035022 DOI: 10.1016/j.reth.2024.03.015] [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: 12/09/2023] [Revised: 03/03/2024] [Accepted: 03/15/2024] [Indexed: 04/25/2024] Open
Abstract
The severe respiratory effects of the coronavirus disease 2019 (COVID-19) pandemic have necessitated the immediate development of novel treatments. The majority of COVID-19-related fatalities are due to acute respiratory distress syndrome (ARDS). Consequently, this virus causes massive and aberrant inflammatory conditions, which must be promptly managed. Severe respiratory disorders, notably ARDS and acute lung injury (ALI), may be treated safely and effectively using cell-based treatments, mostly employing mesenchymal stem cells (MSCs). Since the high potential of these cells was identified, a great deal of research has been conducted on their use in regenerative medicine and complementary medicine. Multiple investigations have demonstrated that MSCs and their products, especially exosomes, inhibit inflammation. Exosomes serve a critical function in intercellular communication by transporting molecular cargo from donor cells to receiver cells. MSCs and their derived exosomes (MSCs/MSC-exosomes) may improve lung permeability, microbial and alveolar fluid clearance, and epithelial and endothelial repair, according to recent studies. This review focuses on COVID-19-related ARDS clinical studies involving MSCs/MSC-exosomes. We also investigated the utilization of Nano-delivery strategies for MSCs/MSC-exosomes and anti-inflammatory agents to enhance COVID-19 treatment.
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Affiliation(s)
- Mohsen Ghiasi
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | | | - Abdolreza Dayani
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Salimi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ehsan Shokri
- Department of Nanotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
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Hobbs KJ, Bayless R, Sheats MK. A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses. Cells 2024; 13:1489. [PMID: 39273060 PMCID: PMC11394191 DOI: 10.3390/cells13171489] [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: 06/30/2024] [Revised: 08/26/2024] [Accepted: 09/04/2024] [Indexed: 09/15/2024] Open
Abstract
With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.
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Affiliation(s)
- Kallie J. Hobbs
- Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
| | - Rosemary Bayless
- Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
| | - M. Katie Sheats
- Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27526, USA;
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9
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Liu Z, Ge Z, Pan W, Zhang R, Jiang Z, Zhao C, Xue X, Xu Y, Zhang W, Lin L, Chen Z. Development and validation of the PLNA score to predict cytokine storm in acute-phase SFTS patients: A single-center cohort study. Int Immunopharmacol 2024; 136:112288. [PMID: 38823181 DOI: 10.1016/j.intimp.2024.112288] [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: 01/12/2024] [Revised: 04/20/2024] [Accepted: 05/15/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.
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Affiliation(s)
- Zishuai Liu
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Ziruo Ge
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Wei Pan
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, China.
| | - Rongling Zhang
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Zhouling Jiang
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Chenxi Zhao
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Xiaoyu Xue
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Yanli Xu
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, China.
| | - Wei Zhang
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
| | - Ling Lin
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, China.
| | - Zhihai Chen
- Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
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10
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Song X, Xu X, Ren X, Ruan X, Bo J. Therapeutic plasma exchange combined with ribavirin to rescue critical SFTS patients. J Clin Apher 2024; 39:e22131. [PMID: 38850077 DOI: 10.1002/jca.22131] [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: 02/08/2024] [Revised: 05/01/2024] [Accepted: 05/20/2024] [Indexed: 06/09/2024]
Abstract
BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic infectious disease caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Endemic in East Asia, SFTS is characterized by an exceptionally high mortality rate. Presently, there is no established treatment for SFTS, particularly for patients in critical condition. In this study, we collected and analyzed laboratory and clinical data from 92 critically ill patients with SFTS treated at Weihai Municipal Hospital between 2019 and 2022. We hope that our study will provide some hints for the treatment of critically ill patients with SFTS. METHODS A total of 92 critically ill patients with SFTS were included in this study. Of these patients, 45 received treatment with therapeutic plasma exchange (TPE) and ribavirin (referred to as the TPE group), while the remaining patients received only ribavirin (referred to as the non-TPE group). Clinical and laboratory parameters were analyzed retrospectively. RESULTS The results showed significant improvements in multiple laboratory parameters following treatment with TPE and ribavirin, including white blood cell and neutrophil count, lactate dehydrogenase, creatine kinase isoenzyme-MB, prothrombin time, activated partial thromboplastin time, D-Dimer, serum sodium and copies of virus genomes. The combination of TPE with ribavirin demonstrated a significant reduction in mortality rates, with a mortality rate of 20.0% in the TPE group compared to 40.4% in the non-TPE group (P = 0.033). CONCLUSIONS Our findings suggest that critically ill patients with SFTS who received TPE and ribavirin experienced improvements in both clinical and laboratory parameters. These results indicate that TPE combined with ribavirin may represent a promising novel therapeutic approach for managing critically ill patients with SFTS. However, comparative studies of large sample size or randomized clinical trials are warranted to confirm the effectiveness of this combination therapy in the treatment of severe SFTS cases.
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Affiliation(s)
- Xuezhen Song
- Department of Blood Transfusion, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Xiaojun Xu
- Department of Blood Transfusion, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Xiaoning Ren
- Department of Blood Transfusion, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Xiaoxuan Ruan
- Department of Blood Transfusion, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Jinshuang Bo
- Department of Blood Transfusion, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
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11
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Shen J, Li J, Lei Y, Chen Z, Wu L, Lin C. Frontiers and hotspots evolution in cytokine storm: A bibliometric analysis from 2004 to 2022. Heliyon 2024; 10:e30955. [PMID: 38774317 PMCID: PMC11107250 DOI: 10.1016/j.heliyon.2024.e30955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 05/08/2024] [Accepted: 05/08/2024] [Indexed: 05/24/2024] Open
Abstract
Background As a fatal disease, cytokine storm has garnered research attention in recent years. Nonetheless, as the body of related studies expands, a thorough and impartial evaluation of the current status of research on cytokine storms remains absent. Consequently, this study aimed to thoroughly explore the research landscape and evolution of cytokine storm utilizing bibliometric and knowledge graph approaches. Methods Research articles and reviews centered on cytokine storms were retrieved from the Web of Science Core Collection database. For bibliometric analysis, tools such as Excel 365, CiteSpace, VOSviewer, and the Bibliometrix R package were utilized. Results This bibliometric analysis encompassed 6647 articles published between 2004 and 2022. The quantity of pertinent articles and citation frequency exhibited a yearly upward trend, with a sharp increase starting in 2020. Network analysis of collaborations reveals that the United States holds a dominant position in this area, boasting the largest publication count and leading institutions. Frontiers in Immunology ranks as the leading journal for the largest publication count in this area. Stephan A. Grupp, a prominent researcher in this area, has authored the largest publication count and has the second-highest citation frequency. Research trends and keyword evaluations show that the connection between cytokine storm and COVID-19, as well as cytokine storm treatment, are hot topics in research. Furthermore, research on cytokine storm and COVID-19 sits at the forefront in this area. Conclusion This study employed bibliometric analysis to create a visual representation of cytokine storm research, revealing current trends and burgeoning topics in this area for the first time. It will provide valuable insights, helping scholars pinpoint critical research areas and potential collaborators.
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Affiliation(s)
- Junyi Shen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Jiaming Li
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Yuqi Lei
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhengrui Chen
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Lingling Wu
- Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Chunyan Lin
- Department of Teaching and Research Section of Internal Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Islam F, Habib S, Badruddza K, Rahman M, Islam MR, Sultana S, Nessa A. The Association of Cytokines IL-2, IL-6, TNF-α, IFN-γ, and IL-10 With the Disease Severity of COVID-19: A Study From Bangladesh. Cureus 2024; 16:e57610. [PMID: 38707035 PMCID: PMC11069400 DOI: 10.7759/cureus.57610] [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] [Accepted: 04/04/2024] [Indexed: 05/07/2024] Open
Abstract
Introduction Clinically, the early prediction of the severity of COVID-19 is often challenging, as a dramatic change in severity can occur without warning. The severity of COVID-19 disease is associated with an increased level of inflammatory mediators, including cytokines. This study aimed to evaluate the association of the levels of cytokines interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10 with the severity of COVID-19 in Bangladesh. Materials and methods This cross-sectional study included a total of 60 confirmed cases of COVID-19, comprising 30 severe cases (Group A) and 30 non-severe cases (Group B), and 10 healthy individuals (Group C) attending Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2021 to February 2022. The cytokine assay was performed using the human Th1/Th2/Th17 cytokine kit BD cytometric bead array (CBA) on the BD Accuri C6 Plus flow cytometer. Statistical analysis was conducted using IBM SPSS Statistics for Windows, Version 23 (Released 2015; IBM Corp., Armonk, New York). Results The mean ages of the patients in Groups A, B, and C were 60.73±5.97, 57.13±7.68, and 48.10±9.13 years, respectively, with a male predominance in all groups. The mean IL-2, IL-6, IL-10, and TNF-α levels had a positive correlation with the increased age group and male gender, although it was not statistically significant. The mean IL-6 and IFN-γ levels were significantly higher among severe cases (216.95±147.78 and 0.98±0.95 pg/mL, respectively) compared to non-severe cases (94.29±128.79 and 0.41±0.61 pg/mL, respectively) and healthy individuals (1.08±1.97 and 0.15±0.28 pg/mL, respectively). Furthermore, the anti-inflammatory cytokine IL-10 was also significantly higher among severe cases (17.92±21.87 pg/mL) compared to non-severe cases (5.38±6.73 pg/mL) and healthy individuals (1.62±1.65 pg/mL). Conclusion IL-6, IFN-γ, and IL-10 have a significant association with the severity of COVID-19 disease. Clinicians treating patients with COVID-19 can consider the level of these cytokines as biomarkers of severity.
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Affiliation(s)
- Farzana Islam
- Division of Laboratory Service, Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, BGD
| | - Shahriar Habib
- Department of Microbiology, Sher-E-Bangla Medical College, Barishal, BGD
| | - Khaja Badruddza
- Department of Biochemistry, Sher-E-Bangla Medical College, Barishal, BGD
| | - Mahatabur Rahman
- Department of Gastroenterology, Sheikh Russel National Gastro-Liver Institute, Dhaka, BGD
| | - Mohammad R Islam
- Department of Anesthesia, Mainamoti Medical College and Hospital, Cumilla, BGD
| | - Sharmin Sultana
- Department of Virology, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Afzalun Nessa
- Department of Virology, Bangabandhu Sheikh Mujjib Medical University, Dhaka, BGD
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13
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Liu Y, Zhu Q, Guo G, Xie Z, Li S, Lai C, Wu Y, Wang L, Zhong S. Causal associations of genetically predicted gut microbiota and blood metabolites with inflammatory states and risk of infections: a Mendelian randomization analysis. Front Microbiol 2024; 15:1342653. [PMID: 38585702 PMCID: PMC10995310 DOI: 10.3389/fmicb.2024.1342653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 02/28/2024] [Indexed: 04/09/2024] Open
Abstract
Background Inflammation serves as a key pathologic mediator in the progression of infections and various diseases, involving significant alterations in the gut microbiome and metabolism. This study aims to probe into the potential causal relationships between gut microbial taxa and human blood metabolites with various serum inflammatory markers (CRP, SAA1, IL-6, TNF-α, WBC, and GlycA) and the risks of seven common infections (gastrointestinal infections, dysentery, pneumonia, bacterial pneumonia, bronchopneumonia and lung abscess, pneumococcal pneumonia, and urinary tract infections). Methods Two-sample Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), maximum likelihood, MR-Egger, weighted median, and MR-PRESSO. Results After adding other MR models and sensitivity analyses, genus Roseburia was simultaneously associated adversely with CRP (Beta IVW = -0.040) and SAA1 (Beta IVW = -0.280), and family Bifidobacteriaceae was negatively associated with both CRP (Beta IVW = -0.034) and pneumonia risk (Beta IVW = -0.391). After correction by FDR, only glutaroyl carnitine remained significantly associated with elevated CRP levels (Beta IVW = 0.112). Additionally, threonine (Beta IVW = 0.200) and 1-heptadecanoylglycerophosphocholine (Beta IVW = -0.246) were found to be significantly associated with WBC levels. Three metabolites showed similar causal effects on different inflammatory markers or infectious phenotypes, stearidonate (18:4n3) was negatively related to SAA1 and urinary tract infections, and 5-oxoproline contributed to elevated IL-6 and SAA1 levels. In addition, 7-methylguanine showed a positive correlation with dysentery and bacterial pneumonia. Conclusion This study provides novel evidence confirming the causal effects of the gut microbiome and the plasma metabolite profile on inflammation and the risk of infection. These potential molecular alterations may aid in the development of new targets for the intervention and management of disorders associated with inflammation and infections.
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Affiliation(s)
- Yingjian Liu
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
| | - Qian Zhu
- Department of Neurosurgery, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou, Guangdong, China
| | - Gongjie Guo
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Zhipeng Xie
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Senlin Li
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Chengyang Lai
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Yonglin Wu
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Liansheng Wang
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Shilong Zhong
- Department of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China
- School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
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14
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Aragane M, Matsumoto L, Yasuda H, Nosaka M, Ishida Y, Yamamoto H, Kondo T, Ishigami A. An autopsy case of fatal Japanese spotted fever in Wakayama. Leg Med (Tokyo) 2024; 66:102355. [PMID: 38043152 DOI: 10.1016/j.legalmed.2023.102355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/26/2023] [Accepted: 11/12/2023] [Indexed: 12/05/2023]
Abstract
Japanese spotted fever (JSF) is potentially fatal infection transmitted by tick bites which vectors Rickettsia (R.) japonica. Since JSF was first described in 1984, the incidence has gradually been increased. We experienced a case of JSF of fatal outcome. A female in 70's was found dead on her bed, whose house was so called 'hoarding house' filled with many waists and unused items. The following day, the autopsy was performed. As representative symptom of external findings, skin rashes were seen on the trunk and extremities, and there were tick-bite eschars on the left upper arm. Internal findings showed no specific findings in each organ. Histopathological examination demonstrated massive inflammatory cell infiltrates mainly consisted of neutrophils in the dermis beneath the external eschar. Furthermore, destruction of glomeruli in kidney with microhemorrhage from mesangial regions was observed. The numerous inflammatory infiltrates were also observed in pulmonary interstitium, which were accompanied with histopathologic features of vasculitis. Biochemical examination showed severe systemic inflammation as monitored by elevated CRP of 16 mg/dL and renal dysfunction by BUN of 171.2 mg/dL and creatinine of 6.07 mg/dL. Subsequently polymerase chain reaction revealed specifically amplified signals for R. japonica from the samples of tick-bites eschar and blood. Thus, we diagnosed her cause of death as JSF which had been occurred multiorgan failure such as acute renal failure and possibly acute respiratory failure. (224 terms).
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Affiliation(s)
- Miki Aragane
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Lennon Matsumoto
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Haruki Yasuda
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Mizuho Nosaka
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Yuko Ishida
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Hiroki Yamamoto
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Toshikazu Kondo
- Department of Forensic Medicine, Wakayama Medical University, Japan
| | - Akiko Ishigami
- Department of Forensic Medicine, Wakayama Medical University, Japan.
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15
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Ionescu (Miron) AI, Atasiei DI, Ionescu RT, Ultimescu F, Barnonschi AA, Anghel AV, Anghel CA, Antone-Iordache IL, Mitre R, Bobolocu AM, Zamfir A, Lișcu HD, Coniac S, Șandru F. Prediction of Subclinical and Clinical Multiple Organ Failure Dysfunction in Breast Cancer Patients-A Review Using AI Tools. Cancers (Basel) 2024; 16:381. [PMID: 38254870 PMCID: PMC11154446 DOI: 10.3390/cancers16020381] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/07/2024] [Accepted: 01/13/2024] [Indexed: 01/24/2024] Open
Abstract
This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question "Why patients with breast cancer exhibit a tendency to deteriorate", this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient's demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as "MODS", "SIRS", "sepsis", "pathophysiology of MODS", "MODS in cancer patients", "multiple organ failure", "risk factors", "cancer", "ICU", "quality of life", and "breast cancer". Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process.
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Affiliation(s)
- Andreea-Iuliana Ionescu (Miron)
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
- Department of Medical Oncology, Colțea Clinical Hospital, 030167 Bucharest, Romania;
| | - Dimitrie-Ionut Atasiei
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Radu-Tudor Ionescu
- Department of Computer Science, University of Bucharest, 010041 Bucharest, Romania;
| | - Flavia Ultimescu
- Department of Pathology, Institute of Oncology “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania;
- Department of Pathological Anatomy, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Andrei-Alexandru Barnonschi
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Alexandra-Valentina Anghel
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Cătălin-Alexandru Anghel
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Ionuț-Lucian Antone-Iordache
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Ruxandra Mitre
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
- Department of Medical Oncology, Colțea Clinical Hospital, 030167 Bucharest, Romania;
| | - Alexandra Maria Bobolocu
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Andreea Zamfir
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
| | - Horia-Dan Lișcu
- Department of Oncological Radiotherapy and Medical Imaging, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (A.-I.I.); (A.-A.B.); (A.-V.A.); (C.-A.A.); (I.-L.A.-I.); (R.M.); (A.M.B.); (A.Z.); (H.-D.L.)
- Department of Radiotherapy, Colțea Clinical Hospital, 030167 Bucharest, Romania
| | - Simona Coniac
- Department of Medical Oncology, Colțea Clinical Hospital, 030167 Bucharest, Romania;
- Department of Endocrinology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Florica Șandru
- Department of Dermatovenerology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
- Department of Dermatology, Elias University Emergency Hospital, 011461 Bucharest, Romania
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Salvetat ML, Zeppieri M. Management of COVID-19 in Ophthalmology. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1457:401-429. [PMID: 39283440 DOI: 10.1007/978-3-031-61939-7_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/31/2024]
Abstract
From its outbreak in early 2020, the new SARS-CoV-2 infection has deeply affected the entire eye care system for several reasons. Since the beginning of the COVID-19 pandemic, ophthalmologists were among the "high-risk category" for contracting the SARS-CoV-2 infection based on the notion that the eye was suspected to be a site of inoculation, infection, and transmission. Clinical ophthalmologists have been required to learn and promptly recognize the ocular manifestations associated with the COVID-19 disease, with its treatments and vaccinations. Restriction measures, lockdown periods, guidelines to prevent SARS-CoV-2 infection transmission, and the use of telemedicine and artificial intelligence modalities have induced profound modifications. These changes, which are most likely to be irreversible, influence routine clinical practice, education, and research, thus giving rise to a "new ophthalmology in the COVID era". This book chapter aims to provide several notions regarding COVID-19 in ophthalmology, including the SARS-CoV-2 virus infection and transmission modalities; the ocular manifestation associated with the COVID-19 disease; the drugs and vaccines used for COVID-19; the precautions adopted in the ophthalmic practice to limit the spread of the virus; the consequences of the pandemic on the ophthalmic patients, clinicians, and the entire eye care system; and, the future of ophthalmology in the era of "COVID new normal".
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Affiliation(s)
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, P.le S. Maria della Misericordia 15, 33100, Udine, Italy.
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17
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Olson SA, Osborn BK, Cotton ME, Krocker JD, Koami H, White N, Cardenas JC. Fibrinogen Fragment X Mediates Endothelial Barrier Disruption via Suppression of VE-Cadherin. J Surg Res 2024; 293:639-646. [PMID: 37837820 PMCID: PMC10726297 DOI: 10.1016/j.jss.2023.09.027] [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: 03/01/2023] [Revised: 09/03/2023] [Accepted: 09/12/2023] [Indexed: 10/16/2023]
Abstract
INTRODUCTION Major traumatic injury is associated with early hemorrhage-related and late-stage deaths due to multiple organ failure (MOF). While improvements to hemostatic resuscitation have significantly reduced hemorrhage-related deaths, the incidence of MOF among trauma patients remains high. Dysregulation of vascular endothelial cell (EC) barrier function is a central mechanism in the development of MOF; however, the mechanistic triggers remain unknown. Accelerated fibrinolysis occurs in a majority of trauma patients, resulting in high circulating levels of fibrin(ogen) degradation products, such as fragment X. To date, the relationship between fragment X and EC dysregulation and barrier disruption is unknown. The goal of this study was to determine the effects of fragment X on EC barrier integrity and expression of paracellular junctional proteins that regulate barrier function. METHODS Human lung microvascular endothelial cells (HLMVECs) were treated with increasing concentrations of fragment X (1, 10, and 100 μg/mL), and barrier function was monitored using the xCELLigence live-cell monitoring system. Quantitative PCR (qPCR) was performed to measure changes in EC expression of 84 genes. Immunofluorescent (IF) cytostaining was performed to validate qPCR findings. RESULTS Fragment X treatment significantly increased endothelial permeability over time (P < 0.05). There was also a significant reduction in VE-cadherin mRNA expression in fragment X-treated HLMVECs compared to control (P = 0.01), which was confirmed by IF staining. CONCLUSIONS Fragment X may induce EC hyperpermeability by reducing VE-cadherin expression. This suggests that a targeted approach to disrupting EC-fragment X interactions could mitigate EC barrier disruption, organ edema, and MOF associated with major trauma.
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Affiliation(s)
- Sarah A Olson
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas
| | - Baron K Osborn
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas
| | - Madeline E Cotton
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas
| | - Joseph D Krocker
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas
| | - Hiroyuki Koami
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas
| | - Nathan White
- Department of Emergency Medicine and Resuscitation Engineering Science Unit, University of Washington School of Medicine, Seattle, Washington
| | - Jessica C Cardenas
- Department of Surgery, Center for Translational Injury Research, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, Texas.
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18
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Lv B, Huang S, Huang H, Niu N, Liu J. Endothelial Glycocalyx Injury in SARS-CoV-2 Infection: Molecular Mechanisms and Potential Targeted Therapy. Mediators Inflamm 2023; 2023:6685251. [PMID: 37674786 PMCID: PMC10480029 DOI: 10.1155/2023/6685251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 07/05/2023] [Accepted: 08/17/2023] [Indexed: 09/08/2023] Open
Abstract
This review aims at summarizing state-of-the-art knowledge on glycocalyx and SARS-CoV-2. The endothelial glycocalyx is a dynamic grid overlying the surface of the endothelial cell (EC) lumen and consists of membrane-bound proteoglycans and glycoproteins. The role of glycocalyx has been determined in the regulation of EC permeability, adhesion, and coagulation. SARS-CoV-2 is an enveloped, single-stranded RNA virus belonging to β-coronavirus that causes the outbreak and the pandemic of COVID-19. Through the respiratory tract, SARS-CoV-2 enters blood circulation and interacts with ECs possessing angiotensin-converting enzyme 2 (ACE2). Intact glycolyx prevents SARS-CoV-2 invasion of ECs. When the glycocalyx is incomplete, virus spike protein of SARS-CoV-2 binds with ACE2 and enters ECs for replication. In addition, cytokine storm targets glycocalyx, leading to subsequent coagulation disorder. Therefore, it is intriguing to develop a novel treatment for SARS-CoV-2 infection through the maintenance of the integrity of glycocalyx. This review aims to summarize state-of-the-art knowledge of glycocalyx and its potential function in SARS-CoV-2 infection.
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Affiliation(s)
- Bingxuan Lv
- The Second Hospital of Shandong University, Shandong University, 247 Beiyuan Street, Jinan 250033, China
| | - Shengshi Huang
- Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China
| | - Hong Huang
- Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China
| | - Na Niu
- Department of Pediatrics, Shandong Provincial Hospital, Shandong First Medical University, 324 Jingwu Road, Jinan 250021, China
| | - Ju Liu
- Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, China
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Imam MT, Almalki ZS, Alzahrani AR, Al-Ghamdi SS, Falemban AH, Alanazi IM, Shahzad N, Muhammad Alrooqi M, Jabeen Q, Shahid I. COVID-19 and severity of liver diseases: Possible crosstalk and clinical implications. Int Immunopharmacol 2023; 121:110439. [PMID: 37315370 PMCID: PMC10247890 DOI: 10.1016/j.intimp.2023.110439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/30/2023] [Accepted: 05/31/2023] [Indexed: 06/16/2023]
Abstract
COVID-19-infected individuals and those who recovered from the infection have been demonstrated to have elevated liver enzymes or abnormal liver biochemistries, particularly with preexisting liver diseases, liver metabolic disorders, viral hepatitis, and other hepatic comorbidities. However, possible crosstalk and intricate interplay between COVID-19 and liver disease severity are still elusive, and the available data are murky and confined. Similarly, the syndemic of other blood-borne infectious diseases, chemical-induced liver injuries, and chronic hepatic diseases continued to take lives while showing signs of worsening due to the COVID-19 crisis. Moreover, the pandemic is not over yet and is transitioning to becoming an epidemic in recent years; hence, monitoring liver function tests (LFTs) and assessing hepatic consequences of COVID-19 in patients with or without liver illnesses would be of paramount interest. This pragmatic review explores the correlations between COVID-19 and liver disease severity based on abnormal liver biochemistries and other possible mechanisms in individuals of all ages from the emergence of the COVID-19 pandemic to the post-pandemic period. The review also alludes to clinical perspectives of such interactions to curb overlapping hepatic diseases in people who recovered from the infection or living with long COVID-19.
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Affiliation(s)
- Mohammad T Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Ziyad S Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj 11942, Saudi Arabia
| | - Abdullah R Alzahrani
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Saeed S Al-Ghamdi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Alaa H Falemban
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Ibrahim M Alanazi
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia
| | | | - Qaisar Jabeen
- Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Imran Shahid
- Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, Makkah 21955, Saudi Arabia.
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20
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Mátyás BB, Benedek I, Blîndu E, Gerculy R, Roșca A, Rat N, Kovács I, Opincariu D, Parajkó Z, Szabó E, Benedek B, Benedek T. Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection. Int J Mol Sci 2023; 24:ijms24087398. [PMID: 37108558 PMCID: PMC10138327 DOI: 10.3390/ijms24087398] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/14/2023] [Accepted: 04/15/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.
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Affiliation(s)
- Botond Barna Mátyás
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Imre Benedek
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Department of Cardiology, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
| | - Emanuel Blîndu
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Renáta Gerculy
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Aurelian Roșca
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Nóra Rat
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Department of Cardiology, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
| | - István Kovács
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Department of Cardiology, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
| | - Diana Opincariu
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Department of Cardiology, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
| | - Zsolt Parajkó
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Evelin Szabó
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu-Mures, Romania
| | - Bianka Benedek
- Faculty of Medicine and Pharmacy, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
| | - Theodora Benedek
- Clinic of Cardiology, Mureș County Emergency Clinical Hospital, 540142 Târgu Mureș, Romania
- Center of Advanced Research in Multimodality Cardiac Imaging, CardioMed Medical Center, 540124 Târgu Mureș, Romania
- Department of Cardiology, University of Medicine, Pharmacy, Science and Technology "George Emil Palade" of Târgu-Mures, 540139 Târgu Mureș, Romania
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21
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Luo J, Zhang Z, Zhao S, Gao R. A Comparison of Etiology, Pathogenesis, Vaccinal and Antiviral Drug Development between Influenza and COVID-19. Int J Mol Sci 2023; 24:ijms24076369. [PMID: 37047339 PMCID: PMC10094131 DOI: 10.3390/ijms24076369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 03/15/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Influenza virus and coronavirus, two kinds of pathogens that exist widely in nature, are common emerging pathogens that cause respiratory tract infections in humans. In December 2019, a novel coronavirus SARS-CoV-2 emerged, causing a severe respiratory infection named COVID-19 in humans, and raising a global pandemic which has persisted in the world for almost three years. Influenza virus, a seasonally circulating respiratory pathogen, has caused four global pandemics in humans since 1918 by the emergence of novel variants. Studies have shown that there are certain similarities in transmission mode and pathogenesis between influenza and COVID-19, and vaccination and antiviral drugs are considered to have positive roles as well as several limitations in the prevention and control of both diseases. Comparative understandings would be helpful to the prevention and control of these diseases. Here, we review the study progress in the etiology, pathogenesis, vaccine and antiviral drug development for the two diseases.
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Zielińska A, Eder P, Karczewski J, Szalata M, Hryhorowicz S, Wielgus K, Szalata M, Dobrowolska A, Atanasov AG, Słomski R, Souto EB. Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review. Front Immunol 2023; 14:1147991. [PMID: 37033914 PMCID: PMC10073701 DOI: 10.3389/fimmu.2023.1147991] [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: 01/19/2023] [Accepted: 03/06/2023] [Indexed: 04/11/2023] Open
Abstract
Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.
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Affiliation(s)
| | - Piotr Eder
- Department of Gastroenterology, Dietetics, and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Jacek Karczewski
- Department of Environmental Medicine/Department of Gastroenterology, Human Nutrition and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
| | - Marlena Szalata
- Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland
| | - Szymon Hryhorowicz
- Institute of Human Genetics, Polish Academy of Sciences Poznan, Poznan, Poland
| | - Karolina Wielgus
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Milena Szalata
- Department of Biotechnology, Institute of Natural Fibres and Medicinal Plants National Research Institute, Poznan, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics, and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland
| | - Atanas G. Atanasov
- Institute of Genetics and Animal Biotechnology, Magdalenka, Poland
- Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
- Department of Pharmacognosy, University of Vienna, Vienna, Austria
| | - Ryszard Słomski
- Institute of Human Genetics, Polish Academy of Sciences Poznan, Poznan, Poland
| | - Eliana B. Souto
- UCIBIO – Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
- Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal
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Sun S, Chen R, Dou X, Dai M, Long J, Wu Y, Lin Y. Immunoregulatory mechanism of acute kidney injury in sepsis: A Narrative Review. Biomed Pharmacother 2023; 159:114202. [PMID: 36621143 DOI: 10.1016/j.biopha.2022.114202] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/17/2022] [Accepted: 12/30/2022] [Indexed: 01/08/2023] Open
Abstract
Sepsis acute kidney injury (SAKI) is a common complication of sepsis, accounting for 26-50 % of all acute kidney injury (AKI). AKI is an independent risk factor for increased mortality risk in patients with sepsis. The excessive inflammatory cascade reaction in SAKI is one of the main causes of kidney damage. Both the innate immune system and the adaptive immune system are involved in the inflammation process of SAKI. Under the action of endotoxin, neutrophils, monocytes, macrophages, T cells and other complex immune network reactions occur, and a large number of endogenous inflammatory mediators are released, resulting in the amplification and loss of control of the inflammatory response. The study of immune cells in SAKI will help improve the understanding of the immune mechanisms of SAKI, and will lay a foundation for the development of new diagnostic and therapeutic targets. This article reviews the role of known immune mechanisms in the occurrence and development of SAKI, with a view to finding new targets for SAKI treatment.
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Affiliation(s)
- Shujun Sun
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Rui Chen
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xiaoke Dou
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Maosha Dai
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Junhao Long
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yan Wu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
| | - Yun Lin
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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24
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Liu Z, Deng P, Liu S, Bian Y, Xu Y, Zhang Q, Wang H, Pi J. Is Nuclear Factor Erythroid 2-Related Factor 2 a Target for the Intervention of Cytokine Storms? Antioxidants (Basel) 2023; 12:antiox12010172. [PMID: 36671034 PMCID: PMC9855012 DOI: 10.3390/antiox12010172] [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: 12/10/2022] [Revised: 01/08/2023] [Accepted: 01/09/2023] [Indexed: 01/13/2023] Open
Abstract
The term "cytokine storm" describes an acute pathophysiologic state of the immune system characterized by a burst of cytokine release, systemic inflammatory response, and multiple organ failure, which are crucial determinants of many disease outcomes. In light of the complexity of cytokine storms, specific strategies are needed to prevent and alleviate their occurrence and deterioration. Nuclear factor erythroid 2-related factor 2 (NRF2) is a CNC-basic region-leucine zipper protein that serves as a master transcription factor in maintaining cellular redox homeostasis by orchestrating the expression of many antioxidant and phase II detoxification enzymes. Given that inflammatory response is intertwined with oxidative stress, it is reasonable to assume that NRF2 activation limits inflammation and thus cytokine storms. As NRF2 can mitigate inflammation at many levels, it has emerged as a potential target to prevent and treat cytokine storms. In this review, we summarized the cytokine storms caused by different etiologies and the rationale of interventions, focusing mainly on NRF2 as a potential therapeutic target.
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Affiliation(s)
- Zihang Liu
- The First Department of Clinical Medicine, China Medical University, Shenyang 110122, China
| | - Panpan Deng
- The First Department of Clinical Medicine, China Medical University, Shenyang 110122, China
| | - Shengnan Liu
- Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China
| | - Yiying Bian
- Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China
| | - Yuanyuan Xu
- Group of Chronic Disease and Environmental Genomics, School of Public Health, China Medical University, Shenyang 110122, China
| | - Qiang Zhang
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
| | - Huihui Wang
- Group of Chronic Disease and Environmental Genomics, School of Public Health, China Medical University, Shenyang 110122, China
- Correspondence: (H.W.); or (J.P.)
| | - Jingbo Pi
- Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang 110122, China
- Correspondence: (H.W.); or (J.P.)
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25
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Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model. Respir Res 2023; 24:66. [PMID: 36864506 PMCID: PMC9978286 DOI: 10.1186/s12931-023-02336-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 01/18/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND COVID-19 is characterized by severe acute lung injury, which is associated with neutrophil infiltration and the release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. METHODS Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. SARS-CoV-2-infected K18-hACE2 mice were performed for clinical sickness scores and lung pathology. Moreover, the levels of NETs were assessed and lung injuries were by histopathology and TUNEL assay. Finally, the injury in the heart and kidney was assessed by histopathology and biochemical-specific markers. RESULTS DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potentially deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. CONCLUSIONS Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.
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Liao H, Ye J, Gao Y, Lian C, Liu L, Xu X, Feng Y, Yang Y, Yang Y, Shen Q, Gao L, Liu Z, Liu Y. Baicalein self-microemulsion based on drug-phospholipid complex for the alleviation of cytokine storm. Bioeng Transl Med 2023; 8:e10357. [PMID: 36684101 PMCID: PMC9842031 DOI: 10.1002/btm2.10357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 05/01/2022] [Accepted: 05/06/2022] [Indexed: 01/25/2023] Open
Abstract
Cytokine storm is a phenomenon whereby the overreaction of the human immune system leads to the release of inflammatory cytokines, which can lead to multiple organ dysfunction syndrome. At present, the existing drugs for the treatment of cytokine storm have limited efficacy and severe adverse effects. Here, we report a lymphatic targeting self-microemulsifying drug delivery system containing baicalein to effectively inhibit cytokine storm. Baicalein self-microemulsion with phospholipid complex as an intermediate carrier (BAPC-SME) prepared in this study could be spontaneously emulsified to form 12-nm oil-in-water nanoemulsion after administration. And then BAPC-SME underwent uptake by enterocyte through endocytosis mediated by lipid valve and clathrin, and had obvious characteristics of mesenteric lymph node targeting distribution. Oral administration of BAPC-SME could significantly inhibit the increase in plasma levels of 14 cytokines: TNF-α, IL-6, IFN-γ, MCP-1, IL-17A, IL-27, IL-1α, GM-CSF, MIG, IFN-β, IL-12, MIP-3α, IL-23, and RANTES in mice experiencing systemic cytokine storm. BAPC-SME could also significantly improve the pathological injury and inflammatory cell infiltration of lung tissue in mice experiencing local cytokine storm. This study does not only provide a new lymphatic targeted drug delivery strategy for the treatment of cytokine storm but also has great practical significance for the clinical development of baicalein self-microemulsion therapies for cytokine storm.
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Affiliation(s)
- Hengfeng Liao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Jun Ye
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yue Gao
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Chunfang Lian
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Lu Liu
- Research and Development DepartmentBeijing Wehand‐Bio Pharmaceutical Co. LtdBeijingChina
| | - Xiaoyan Xu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yu Feng
- Research and Development DepartmentBeijing Wehand‐Bio Pharmaceutical Co. LtdBeijingChina
| | - Yanfang Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Yuqi Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Qiqi Shen
- Research and Development DepartmentBeijing Wehand‐Bio Pharmaceutical Co. LtdBeijingChina
| | - Lili Gao
- Research and Development DepartmentBeijing Wehand‐Bio Pharmaceutical Co. LtdBeijingChina
| | - Zhihua Liu
- Research and Development DepartmentBeijing Wehand‐Bio Pharmaceutical Co. LtdBeijingChina
| | - Yuling Liu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
- Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
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Amra B, Ashrafi F, Torki M, Hashemi M, Shirzadi M, Soltaninejad F, Sadeghi S, Salmasi M, Sami R, Darakhshandeh A, Nasirian M, Pourajam S. Thalidomide for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Clinical Trial. Adv Biomed Res 2023; 12:14. [PMID: 36926422 PMCID: PMC10012021 DOI: 10.4103/abr.abr_248_21] [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: 08/08/2021] [Revised: 04/04/2022] [Accepted: 04/20/2022] [Indexed: 02/05/2023] Open
Abstract
Background Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2. Materials and Methods An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission. Results From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7-10.3), as compared with days 5.3 (95% CI, 1.7-8.9) with control (odds ratio 0.01; 95% CI, -1.58-1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55-27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05). Conclusion This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.
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Affiliation(s)
- Babak Amra
- Bamdad Respiratory and Sleep Research Center, Department of Internal Medicine, Pulmonary and Sleep Ward, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Farzaneh Ashrafi
- Department of Hematology Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Torki
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marzieh Hashemi
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohamad Shirzadi
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Forogh Soltaninejad
- Bamdad Respiratory and Sleep Research Center, Department of Internal Medicine, Pulmonary and Sleep Ward, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Somayeh Sadeghi
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrzad Salmasi
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ramin Sami
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Darakhshandeh
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Nasirian
- Department of Epidemiology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Samaneh Pourajam
- Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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S A, K G, A AM. Intermodulation of gut-lung axis microbiome and the implications of biotics to combat COVID-19. J Biomol Struct Dyn 2022; 40:14262-14278. [PMID: 34699326 DOI: 10.1080/07391102.2021.1994875] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The novel coronavirus disease pandemic caused by the COVID-19 virus has infected millions of people around the world with a surge in transmission and mortality rates. Although it is a respiratory viral infection that affects airway epithelial cells, a diverse set of complications, including cytokine storm, gastrointestinal disorders, neurological distress, and hyperactive immune responses have been reported. However, growing evidence indicates that the bidirectional crosstalk of the gut-lung axis can decipher the complexity of the disease. Though not much research has been focused on the gut-lung axis microbiome, there is a translocation of COVID-19 infection from the lung to the gut through the lymphatic system resulting in disruption of gut permeability and its integrity. It is believed that detailed elucidation of the gut-lung axis crosstalk and the role of microbiota can unravel the most significant insights on the discovery of diagnosis using microbiome-based-therapeutics for COVID-19. This review calls attention to relate the influence of dysbiosis caused by COVID-19 and the involvement of the gut-lung axis. It presents first of its kind details that concentrate on the momentousness of biotics in disease progression and restoration. Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Aishwarya S
- Department of Bioinformatics, Stella Maris College, Chennai, India.,Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Chennai, India
| | - Gunasekaran K
- Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Chennai, India
| | - Anita Margret A
- Department of Biotechnology and Bioinformatics, Bishop Heber College, Tiruchirappalli, Tamil Nadu, India
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Tews HC, Kandulski A, Schmid S, Schlosser S, Schirner S, Putz FJ, Cosma L, Gülow K, Müller M, Jung EM. Multimodal ultrasound imaging with conventional B-mode, elastography, and parametric analysis of contrast-enhanced ultrasound (CEUS): A novel approach to assess small bowel manifestation in severe COVID-19 disease. Clin Hemorheol Microcirc 2022; 82:341-360. [PMID: 35871323 DOI: 10.3233/ch-221540] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The aim was to describe the small bowel morphology with conventional B-mode and elastography and additionally to evaluate dynamic effects of COVID-19 associated small bowel microvascularization using CEUS with color coded perfusion parameters.Thirteen patients with severe COVID-19 acute respiratory distress syndrome (ARDS) were investigated. 13 patients required intensive care treatment with mechanical ventilation. Five patients required extracorporeal membrane oxygenation (ECMO). Contrast-enhanced ultrasound (CEUS) was performed by an experienced investigator as a bolus injection of up to 2.4 ml sulfur hexafluoride microbubbles via a central venous catheter. In the parametric analysis of CEUS, the flare of microbubbles over time is visualized with colors. This is the first work using parametric analysis of CEUS to detect perfusion differences in the small bowel.Parametric analysis of CEUS in the intestinal phase was carried out, using DICOM loops for 20 seconds. In 5 patients, parametric analysis revealed intraindividual differences in contrast agent behavior in the small bowel region. Analogous to the computed tomography (CT) images parametric analysis showed regions of simultaneous hyper- and hypoperfusion of the small intestine in a subgroup of patients. In 5 patients, the parametric image of transmural global contrast enhancement was visualized.Our results using CEUS to investigate small bowel affection in COVID-19 suggest that in severe COVID-19 ARDS systemic inflammation and concomitant micro embolisms may lead to disruption of the epithelial barrier of the small intestine.This is the first study using parametric analysis of CEUS to evaluate the extent of small bowel involvement in severe COVID-19 disease and to detect microemboli. In summary, we show that in COVID-19 the small bowel may also be an important interaction site. This is in line with the fact that enterocytes have been shown to a plenitude of angiotensin converting enzyme (ACE)-2 receptors as entry sites of the virus.
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Affiliation(s)
- H C Tews
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - A Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - S Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - S Schlosser
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - S Schirner
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - F J Putz
- Department of Nephrology, University Hospital Regensburg, Regensburg, Germany
| | - L Cosma
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - K Gülow
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - M Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - E M Jung
- Department of Radiology, University Hospital Regensburg, Regensburg, Germany
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Nazerian Y, Ghasemi M, Yassaghi Y, Nazerian A, Mahmoud Hashemi S. Role of SARS-CoV-2-induced Cytokine Storm in Multi-Organ Failure: Molecular Pathways and Potential Therapeutic Options. Int Immunopharmacol 2022; 113:109428. [PMID: 36379152 PMCID: PMC9637536 DOI: 10.1016/j.intimp.2022.109428] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/19/2022] [Accepted: 11/01/2022] [Indexed: 11/09/2022]
Abstract
Coronavirus disease 2019 (COVID-19) outbreak has become a global public health emergency and has led to devastating results. Mounting evidence proposes that the disease causes severe pulmonary involvement and influences different organs, leading to a critical situation named multi-organ failure. It is yet to be fully clarified how the disease becomes so deadly in some patients. However, it is proven that a condition called “cytokine storm” is involved in the deterioration of COVID-19. Although beneficial, sustained production of cytokines and overabundance of inflammatory mediators causing cytokine storm can lead to collateral vital organ damages. Furthermore, cytokine storm can cause post-COVID-19 syndrome (PCS), an important cause of morbidity after the acute phase of COVID-19. Herein, we aim to explain the possible pathophysiology mechanisms involved in COVID-19-related cytokine storm and its association with multi-organ failure and PCS. We also discuss the latest advances in finding the potential therapeutic targets to control cytokine storm wishing to answer unmet clinical demands for treatment of COVID-19.
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Affiliation(s)
- Yasaman Nazerian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Ghasemi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Younes Yassaghi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Seyed Mahmoud Hashemi
- Medical nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Corresponding author at: Medical nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran / Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Severity of COVID-19 patients with coexistence of asthma and vitamin D deficiency. INFORMATICS IN MEDICINE UNLOCKED 2022; 34:101116. [PMID: 36338941 PMCID: PMC9616486 DOI: 10.1016/j.imu.2022.101116] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/21/2022] [Accepted: 10/22/2022] [Indexed: 11/06/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19)-driven global pandemic triggered innumerable health complications, imposing great challenges in managing other respiratory diseases like asthma. Furthermore, increases in the underlying inflammation involved in the fatality of COVID-19 have been linked with lack of vitamin D. In this research work, we intend to investigate the possible genetic linkage of asthma and vitamin D deficiency with the severity and fatality of COVID-19 using a network-based approach. We identified and analysed 41 and 14 differentially expressed genes (DEGs) of COVID-19 being common with asthma and vitamin D deficiency, respectively, through the comparative differential gene expression analysis and their footprints on signalling pathways. Gene set enrichment analysis for GO terms and signalling pathways reveals key biological activities, including inflammatory response-related pathways (e.g., cytokine- and chemokine-mediated signalling pathways, IL-17, and TNF signalling pathways). Besides, the Protein–Protein Interaction network analysis of those DEGs reveals hub proteins, some of which are reported as inflammatory antiviral interferon-stimulated biomarkers that potentially drive the cytokine storm leading to COVID-19 severity and fatality, and contributes in the early stage of viral replication, respectively. Moreover, the regulatory network analysis found these DEGs associated with antiviral and tumour inhibitory transcription factors and micro-RNAs. Finally, drug–target enrichment analysis yields tetradioxin, estradiol, arsenenous acid, and zinc, which have been reported to be effective in suppressing the pro-inflammatory cytokines production, and other respiratory tract infections. Our results yield shared biomarker-driven key hypotheses followed by network-based analytics, demystifying the mechanistic details of COVID-19 comorbidity of asthma and vitamin D deficiency with their potential therapeutic implications.
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Sokouti B. A systems biology approach for investigating significantly expressed genes among COVID-19, hepatocellular carcinoma, and chronic hepatitis B. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2022; 23:146. [PMID: 37521843 PMCID: PMC9584277 DOI: 10.1186/s43042-022-00360-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 10/12/2022] [Indexed: 01/08/2023] Open
Abstract
Background Worldwide, COVID-19's death rate is about 2%, considering the incidence and mortality. However, the information on its complications in other organs, specifically the liver and its disorders, is limited in mild or severe cases. In this study, we aimed to computationally investigate the typical relationships between liver-related diseases [i.e., hepatocellular carcinoma (HCC), and chronic hepatitis B (CHB)] and COVID-19, considering the involved significant genes and their molecular mechanisms. Methods We investigated two GEO microarray datasets (GSE164805 and GSE58208) to identify differentially expressed genes (DEGs) among the generated four datasets for mild/severe COVID-19, HCC, and CHB. Then, the overlapping genes among them were identified for GO and KEGG enrichment analyses, protein-protein interaction network construction, hub genes determination, and their associations with immune cell infiltration. Results A total of 22 significant genes (i.e., ACTB, ATM, CDC42, DHX15, EPRS, GAPDH, HIF1A, HNRNPA1, HRAS, HSP90AB1, HSPA8, IL1B, JUN, POLR2B, PTPRC, RPS27A, SFRS1, SMARCA4, SRC, TNF, UBE2I, and VEGFA) were found to play essential roles among mild/severe COVID-19 associated with HCC and CHB. Moreover, the analysis of immune cell infiltration revealed that these genes are mostly positively correlated with tumor immune and inflammatory responses. Conclusions In summary, the current study demonstrated that 22 identified DEGs might play an essential role in understanding the associations between the mild/severe COVID-19 patients with HCC and CHB. So, the HCC and CHB patients involved in different types of COVID-19 can benefit from immune-based targets for therapeutic interventions. Supplementary Information The online version contains supplementary material available at 10.1186/s43042-022-00360-3.
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Affiliation(s)
- Babak Sokouti
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Wilden A, Glaubitz J, Otto O, Biedenweg D, Nauck M, Mack M, Ribback S, Bröker BM, von Rheinbaben SF, Lerch MM, Aghdassi AA, Weiss FU, Sendler M. Mobilization of CD11b+/Ly6chi monocytes causes multi organ dysfunction syndrome in acute pancreatitis. Front Immunol 2022; 13:991295. [PMID: 36300116 PMCID: PMC9589437 DOI: 10.3389/fimmu.2022.991295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/23/2022] [Indexed: 11/13/2022] Open
Abstract
Objective Acute pancreatitis (AP) is an inflammatory disorder, the severe form of which is burdened with multi-organ dysfunction and high mortality. The pathogenesis of life –threatening organ complications, such as respiratory and renal failure, is unknown. Design Organ dysfunction was investigated in a mouse model of AP. The influence of monocytes and neutrophils on multi organ dysfunction syndrome (MODS) was investigated in vivo by antibody depletion. Using real-time-fluorescence and deformability-cytometry (RT-DC) analysis we determined the mechanical properties of neutrophils and monocytes during AP. Furthermore, blood samples of pancreatitis patients were used to characterize severity-dependent chemokine profiles according to the revised Atlanta classification. Results Similar to AP in humans, severe disease in the mouse model associates with organ dysfunction mainly of lung and kidney, which is triggered by a mobilisation of Ly6g-/CD11b+/Ly6c hi monocytes, but not of Ly6g+/CD11b+ neutrophils. Monocyte depletion by anti-CCR2 antibody treatment ameliorated lung function (oxygen consumption) without interfering with the systemic immune response. RT-DC analysis of circulation monocytes showed a significant increase in cell size during SAP, but without a compensatory increase in elasticity. Patient chemokine profiles show a correlation of AP severity with monocyte attracting chemokines like MCP-1 or MIG and with leukocyte mobilisation. Conclusion In AP, the physical properties of mobilized monocytes, especially their large size, result in an obstruction of the fine capillary systems of the lung and of the kidney glomeruli. A selective depletion of monocytes may represent a treatment strategy for pancreatitis as well as for other inflammation-related disorders.
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Affiliation(s)
- Anika Wilden
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Juliane Glaubitz
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Oliver Otto
- Center for Innovation Competence: Humoral Immune Reactions in Cardiovascular Disorders, University of Greifswald, Greifswald, Germany
| | - Doreen Biedenweg
- Center for Innovation Competence: Humoral Immune Reactions in Cardiovascular Disorders, University of Greifswald, Greifswald, Germany
- Department of Medicine B, University Medicine Greifswald, Greifswald, Germany
| | - Matthias Nauck
- Institute of Clinical Chemistry and Laboratory Diagnostics, University Medicine Greifswald, Greifswald, Germany
- Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK) (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany
| | - Matthias Mack
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Silvia Ribback
- Institute of Pathology, Universitat Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
| | - Barbara M. Bröker
- Department of Immunology, University Medicine Greifswald, Greifswald, Germany
| | | | - Markus M. Lerch
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | | | - Frank Ulrich Weiss
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
| | - Matthias Sendler
- Department of Medicine A, University Medicine Greifswald, Greifswald, Germany
- *Correspondence: Matthias Sendler,
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David S, Dorado G, Duarte EL, David-Bosne S, Trigueiro-Louro J, Rebelo-de-Andrade H. COVID-19: impact on Public Health and hypothesis-driven investigations on genetic susceptibility and severity. Immunogenetics 2022; 74:381-407. [PMID: 35348847 PMCID: PMC8961091 DOI: 10.1007/s00251-022-01261-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022]
Abstract
COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million human beings worldwide, causing an unprecedented coronavirus pandemic. Currently, the international scientific community is engaged in elucidating the molecular mechanisms of the pathophysiology of SARS-CoV-2 infection as a basis of scientific developments for the future control of COVID-19. Global exome and genome analysis efforts work to define the human genetics of protective immunity to SARS-CoV-2 infection. Here, we review the current knowledge regarding the SARS-CoV-2 infection, the implications of COVID-19 to Public Health and discuss genotype to phenotype association approaches that could be exploited through the selection of candidate genes to identify the genetic determinants of severe COVID-19.
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Affiliation(s)
- Susana David
- Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA,IP), Lisboa, Portugal.
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal.
| | - Guillermo Dorado
- Atlántida Centro de Investigación y Desarrollo de Estudios Profesionales (CIDEP), Granada, Spain
| | - Elsa L Duarte
- MED-Instituto Mediterrâneo para a Agricultura, Ambiente e Desenvolvimento, Escola de Ciências e Tecnologia, Universidade de Évora, Évora, Portugal
| | | | - João Trigueiro-Louro
- Departamento de Doenças Infeciosas, INSA, IP, Lisboa, Portugal
- Host-Pathogen Interaction Unit, Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
- Hospital Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal
| | - Helena Rebelo-de-Andrade
- Departamento de Doenças Infeciosas, INSA, IP, Lisboa, Portugal
- Host-Pathogen Interaction Unit, Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisboa, Portugal
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Soltani-Zangbar MS, Parhizkar F, Ghaedi E, Tarbiat A, Motavalli R, Alizadegan A, Aghebati-Maleki L, Rostamzadeh D, Yousefzadeh Y, Jadideslam G, Farid SS, Roshangar L, Mahmoodpoor A, Heris JA, Miahipour A, Yousefi M. A comprehensive evaluation of the immune system response and type-I Interferon signaling pathway in hospitalized COVID-19 patients. Cell Commun Signal 2022; 20:106. [PMID: 35842705 PMCID: PMC9287826 DOI: 10.1186/s12964-022-00903-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 05/22/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The COVID-19 pandemic has become the world's main life-threatening challenge in the third decade of the twenty-first century. Numerous studies have been conducted on SARS-CoV2 virus structure and pathogenesis to find reliable treatments and vaccines. The present study aimed to evaluate the immune-phenotype and IFN-I signaling pathways of COVID-19 patients with mild and severe conditions. MATERIAL AND METHODS A total of 100 COVID-19 patients (50 with mild and 50 with severe conditions) were enrolled in this study. The frequency of CD4 + T, CD8 + T, Th17, Treg, and B lymphocytes beside NK cells was evaluated using flow cytometry. IFN-I downstream signaling molecules, including JAK-1, TYK-2, STAT-1, and STAT-2, and Interferon regulatory factors (IRF) 3 and 7 expressions at RNA and protein status were investigated using real-time PCR and western blotting techniques, respectively. Immune levels of cytokines (e.g., IL-1β, IL-6, IL-17, TNF-α, IL-2R, IL-10, IFN-α, and IFN-β) and the existence of anti-IFN-α autoantibodies were evaluated via enzyme-linked immunosorbent assay (ELISA). RESULTS Immune-phenotyping results showed a significant decrease in the absolute count of NK cells, CD4 + T, CD8 + T, and B lymphocytes in COVID-19 patients. The frequency of Th17 and Treg cells showed a remarkable increase and decrease, respectively. All signaling molecules of the IFN-I downstream pathway and IRFs (i.e., JAK-1, TYK-2, STAT-1, STAT-2, IRF-3, and IRF-7) showed very reduced expression levels in COVID-19 patients with the severe condition compared to healthy individuals at both RNA and protein levels. Of 50 patients with severe conditions, 14 had anti-IFN-α autoantibodies in sera. Meanwhile, this result was 2 and 0 for patients with mild symptoms and healthy controls, respectively. CONCLUSION Our results indicate a positive association of the existence of anti-IFN-α autoantibodies and immune cells dysregulation with the severity of illness in COVID-19 patients. However, comprehensive studies are necessary to find out more about this context. Video abstract.
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Affiliation(s)
- Mohammad Sadegh Soltani-Zangbar
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- grid.412888.f0000 0001 2174 8913Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- grid.412888.f0000 0001 2174 8913Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Forough Parhizkar
- grid.412888.f0000 0001 2174 8913Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- grid.412888.f0000 0001 2174 8913Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Ghaedi
- grid.78028.350000 0000 9559 0613Pirogov Russian National Research Medical University, Moscow, Russia
| | - Ali Tarbiat
- grid.412763.50000 0004 0442 8645Department of Cardiology, Medical Faculty, Urmia University of Medical Sciences, Urmia, Iran
| | - Roza Motavalli
- grid.412888.f0000 0001 2174 8913Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Alizadegan
- grid.412888.f0000 0001 2174 8913Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leili Aghebati-Maleki
- grid.412888.f0000 0001 2174 8913Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Davoud Rostamzadeh
- grid.413020.40000 0004 0384 8939Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
| | - Yousef Yousefzadeh
- grid.412888.f0000 0001 2174 8913Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Golamreza Jadideslam
- grid.412888.f0000 0001 2174 8913Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sima Shahmohammadi Farid
- grid.412888.f0000 0001 2174 8913Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- grid.412888.f0000 0001 2174 8913Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ata Mahmoodpoor
- grid.412888.f0000 0001 2174 8913Department of Anesthesiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Ahmadian Heris
- grid.412888.f0000 0001 2174 8913Department of Allergy and Clinical Immunology, Pediatric Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolfazl Miahipour
- grid.411705.60000 0001 0166 0922Department of Parasitology and Mycology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
| | - Mehdi Yousefi
- grid.412888.f0000 0001 2174 8913Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- grid.412888.f0000 0001 2174 8913Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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The Anti-Cytokine Storm Activity of Quercetin Zinc and Vitamin C Complex. Adv Virol 2022; 2022:1575605. [PMID: 35721668 PMCID: PMC9200564 DOI: 10.1155/2022/1575605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 04/24/2022] [Accepted: 05/04/2022] [Indexed: 11/18/2022] Open
Abstract
Cytokine storm is one of the causative deaths in a patient with severe acute respiratory syndrome. This study aimed at evaluating the prophylaxis effect of quercetin complexes with zinc and buffered ascorbic acid upon cytokine storm induction in mice and identifying the complex's acute toxicity. Mice were randomly divided into three groups: group A, control group, received 0.9% normal saline; group B received 100 mg/kg of the complex one hour before lipopolysaccharide (LPS) administration; and group C received the LPS IP 5 mg/kg. Then, levels of interleukin 1 and interleukin 6 were measured in the serum, and lung and kidney tissues were investigated for any changes that may have happened. Thirty mice were used to investigate the acute toxicity; mice were distributed into six groups: one control group and five treated groups; then several serial dilutions from the complex have been prepared for different concentrations from 5 g/kg to 0.312 g/kg. The animals were observed for 14 days. The LD50 was deduced by the straight-line equation calculated from the dose-response curve. The results in this study showed that group A had no significant tissue change. LPS group C showed tissue damage in the lung and kidney, which significantly prevented by the pretreated complex in group B. Moreover, the complex's acute toxicity value (LD50) was 655 mg/kg. In conclusion, the complex has significantly ameliorated LPS-induced acute lung and kidney injury, largely through suppression of inflammation; the large lethal dose value may make the complex have a promising therapeutic effect in the prevention of cytokine storm.
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Aswad M, Hamza H, Pechkovsky A, Zikrach A, Popov T, Zohar Y, Shahar E, Louria-Hayon I. High-CBD Extract (CBD-X) Downregulates Cytokine Storm Systemically and Locally in Inflamed Lungs. Front Immunol 2022; 13:875546. [PMID: 35651623 PMCID: PMC9149302 DOI: 10.3389/fimmu.2022.875546] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/19/2022] [Indexed: 12/21/2022] Open
Abstract
Cytokine storm refers to the dysregulated production of inflammatory mediators leading to hyperinflammation. They are often detrimental, and worsen the severity of COVID-19 and other infectious or inflammatory diseases. Cannabinoids are known to have anti-inflammatory effects but their possible therapeutic value on cytokine storms has not been fully elucidated. In vivo and ex vivo studies were carried out to investigate the effects of high-THC and high-CBD extracts on cytokine production in immune cells. Significant differences between the extracts were observed. Subsequent experiments focusing on a specific high CBD extract (CBD-X) showed significant reductions in pro-inflammatory cytokines in human-derived PBMCs, neutrophils and T cells. In vivo mouse studies, using a systemically inflamed mouse model, showed reductions in pro-inflammatory cytokines TNFα and IL-1β and a concurrent increase in the anti-inflammatory cytokine IL-10 in response to CBD-X extract treatment. Lung inflammation, as in severe COVID-19 disease, is characterized by increased T-cell homing to the lungs. Our investigation revealed that CBD-X extract impaired T-cell migration induced by the chemoattractant SDF1. In addition, the phosphorylation levels of T cell receptor (TCR) signaling proteins Lck and Zap70 were significantly reduced, demonstrating an inhibitory effect on the early events downstream to TCR activation. In a lung inflamed mouse model, we observed a reduction in leukocytes including neutrophil migration to the lungs and decreased levels of IL-1β, MCP-1, IL-6 and TNFα, in response to the administration of the high-CBD extract. The results presented in this work offer that certain high-CBD extract has a high potential in the management of pathological conditions, in which the secretion of cytokines is dysregulated, as it is in severe COVID-19 disease or other infectious or inflammatory diseases.
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Affiliation(s)
- Miran Aswad
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Haya Hamza
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Antonina Pechkovsky
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Anastasiia Zikrach
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Tania Popov
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel
| | - Yaniv Zohar
- Pathology Department, Rambam Health Care Campus, Haifa, Israel
| | - Eduardo Shahar
- Clinical Immunology Unit, Rambam Health Care Campus, Haifa, Israel
| | - Igal Louria-Hayon
- Medical Cannabis Research and Innovation Center, Rambam Health Care Campus, Haifa, Israel.,Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa, Israel
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Soleimanian S, Alyasin S, Sepahi N, Ghahramani Z, Kanannejad Z, Yaghobi R, Karimi MH. An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19. Front Immunol 2022; 13:884879. [PMID: 35669767 PMCID: PMC9163347 DOI: 10.3389/fimmu.2022.884879] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/20/2022] [Indexed: 12/22/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.
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Affiliation(s)
- Saeede Soleimanian
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soheila Alyasin
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Allergy and Clinical Immunology, Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Najmeh Sepahi
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Ghahramani
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Kanannejad
- Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ramin Yaghobi
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Du J, Li XK, Peng XF, Xu W, Zhang XA, Li H, Yang T, Yuan C, Chen WW, Li C, Lu QB, Liu W. Expansion of granulocytic myeloid-derived suppressor cells in patients with severe fever with thrombocytopenia syndrome. J Med Virol 2022; 94:4329-4337. [PMID: 35562326 DOI: 10.1002/jmv.27854] [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: 03/18/2022] [Revised: 05/05/2022] [Accepted: 05/10/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV) is a hemorrhagic fever with a high mortality rate of over 10%. We have previously shown that granulocytic myeloid-derived suppressor cell (gMDSC) might affect arginine metabolism which was associated with decreased platelet count and T lymphocyte dysfunction in this disease. OBJECTIVES The study was designed to investigate the expression of the gMDSCs subsets in SFTS patients, and to evaluate its association with disease severity. METHODS A prospective study was performed on 166 confirmed SFTSV infected patients. Sequential blood samples were collected during hospitalization and after recovery. SFTSV RNA was quantified by real-time RT-PCR. The gMDSCs and NK cells were determined by Flow cytometry analysis, which were associated with disease severity. RESULTS Elevation of the activated gMDSC was observed in SFTS patients at acute phase, with a significantly higher level of gMDSC attained in 79 severe and 29 fatal SFTS patients than in the mild patients. The NK cells were depleted at the early infection and not restored to normal level until four months after disease. The expansion of gMDSC was accompanied by the elevated expressions of CD3-ζ of NK and Arginase-1, in contrast with the decreased ROS in gMDSC. The levels of NK, CD3-ζ of NK, viral load and platelet count were significantly associated with the level of gMDSC. CONCLUSIONS Expansion of gMDSC was demonstrated in SFTS, which was associated with severe disease and suppressed antiviral NK cell via other mechanism than Arginase-1 or ROS. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Juan Du
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China.,Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, P. R. China
| | - Xiao-Kun Li
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China
| | - Xue-Fang Peng
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China
| | - Wen Xu
- Department of Infectious Disease, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, P. R. China
| | - Xiao-Ai Zhang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China
| | - Hao Li
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China
| | - Tong Yang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China
| | - Chun Yuan
- The 990th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army, Xinyang, Henan province, P. R. China
| | - Wei-Wei Chen
- Department of Infectious Disease, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, P. R. China
| | - Chang Li
- Research Unit of Key Technologies for Prevention and Control of Virus Zoonoses, Chinese Academy of Medical Sciences, Chuangchun, P. R. China
| | - Qing-Bin Lu
- Department of Laboratorial Science and Technology & Vaccine Research Center, School of Public Health, Peking University, Beijing, P. R. China
| | - Wei Liu
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology, and Epidemiology, Beijing, P. R. China.,School of Public Health, Anhui Medical University, Hefei, P. R. China
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Ngai HW, Kim DH, Hammad M, Gutova M, Aboody K, Cox CD. Stem Cell-based therapies for COVID-19-related acute respiratory distress syndrome. J Cell Mol Med 2022; 26:2483-2504. [PMID: 35426198 PMCID: PMC9077311 DOI: 10.1111/jcmm.17265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Revised: 02/24/2022] [Accepted: 02/28/2022] [Indexed: 11/30/2022] Open
Abstract
As the number of confirmed cases and resulting death toll of the COVID-19 pandemic continue to increase around the globe - especially with the emergence of new mutations of the SARS-CoV-2 virus in addition to the known alpha, beta, gamma, delta and omicron variants - tremendous efforts continue to be dedicated to the development of interventive therapeutics to mitigate infective symptoms or post-viral sequelae in individuals for which vaccines are not accessible, viable or effective in the prevention of illness. Many of these investigations aim to target the associated acute respiratory distress syndrome, or ARDS, which induces damage to lung epithelia and other physiologic systems and is associated with progression in severe cases. Recently, stem cell-based therapies have demonstrated preliminary efficacy against ARDS based on a number of preclinical and preliminary human safety studies, and based on promising outcomes are now being evaluated in phase II clinical trials for ARDS. A number of candidate stem cell therapies have been found to exhibit low immunogenicity, coupled with inherent tropism to injury sites. In recent studies, these have demonstrated the ability to modulate suppression of pro-inflammatory cytokine signals such as those characterizing COVID-19-associated ARDS. Present translational studies are aiming to optimize the safety, efficacy and delivery to fully validate stem cell-based strategies targeting COVID-19 associated ARDS for viable clinical application.
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Affiliation(s)
- Hoi Wa Ngai
- Department of Stem Cell Biology and Regenerative MedicineCity of Hope Beckman Research InstituteDuarteCaliforniaUSA
| | - Dae Hong Kim
- Department of Stem Cell Biology and Regenerative MedicineCity of Hope Beckman Research InstituteDuarteCaliforniaUSA
| | - Mohamed Hammad
- Department of Stem Cell Biology and Regenerative MedicineCity of Hope Beckman Research InstituteDuarteCaliforniaUSA
| | - Margarita Gutova
- Department of Stem Cell Biology and Regenerative MedicineCity of Hope Beckman Research InstituteDuarteCaliforniaUSA
| | - Karen Aboody
- Department of Stem Cell Biology and Regenerative MedicineCity of Hope Beckman Research InstituteDuarteCaliforniaUSA
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Onnis C, Muscogiuri G, Paolo Bassareo P, Cau R, Mannelli L, Cadeddu C, Suri JS, Cerrone G, Gerosa C, Sironi S, Faa G, Carriero A, Pontone G, Saba L. Non-invasive coronary imaging in patients with COVID-19: A narrative review. Eur J Radiol 2022; 149:110188. [PMID: 35180580 PMCID: PMC8805958 DOI: 10.1016/j.ejrad.2022.110188] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 01/20/2022] [Accepted: 01/26/2022] [Indexed: 12/14/2022]
Abstract
SARS-CoV-2 infection, responsible for COVID-19 outbreak, can cause cardiac complications, worsening outcome and prognosis. In particular, it can exacerbate any underlying cardiovascular condition, leading to atherosclerosis and increased plaque vulnerability, which may cause acute coronary syndrome. We review current knowledge on the mechanisms by which SARS-CoV-2 can trigger endothelial/myocardial damage and cause plaque formation, instability and deterioration. The aim of this review is to evaluate current non-invasive diagnostic techniques for coronary arteries evaluation in COVID-19 patients, such as coronary CT angiography and atherosclerotic plaque imaging, and their clinical implications. We also discuss the role of artificial intelligence, deep learning and radiomics in the context of coronary imaging in COVID-19 patients.
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Affiliation(s)
- Carlotta Onnis
- Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Polo di Monserrato s.s. 554, Monserrato (Cagliari) 09045, Italy
| | - Giuseppe Muscogiuri
- Department of Radiology, IRCCS Istituto Auxologico Italiano, San Luca Hospital, University Milano Bicocca, Milan, Italy
| | - Pier Paolo Bassareo
- Mater Misericordiae University Hospital and Our Lady's Children's Hospital, University College of Dublin, Crumlin, Dublin, Ireland
| | - Riccardo Cau
- Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Polo di Monserrato s.s. 554, Monserrato (Cagliari) 09045, Italy
| | | | - Christian Cadeddu
- Department of Cardiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Polo di Monserrato s.s. 554, Monserrato (Cagliari) 09045, Italy
| | - Jasjit S Suri
- Stroke Monitoring and Diagnostic Division, AtheroPoint™, Roseville, CA, USA
| | - Giulia Cerrone
- Department of Pathology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Ospedale San Giovanni di, Dio (Cagliari) 09100, Italy
| | - Clara Gerosa
- Department of Pathology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Ospedale San Giovanni di, Dio (Cagliari) 09100, Italy
| | - Sandro Sironi
- Department of Radiology, IRCCS Istituto Auxologico Italiano, San Luca Hospital, University Milano Bicocca, Milan, Italy
| | - Gavino Faa
- Department of Pathology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Ospedale San Giovanni di, Dio (Cagliari) 09100, Italy
| | | | | | - Luca Saba
- Department of Radiology, Azienda Ospedaliero Universitaria (A.O.U.), di Cagliari - Polo di Monserrato s.s. 554, Monserrato (Cagliari) 09045, Italy.
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Zhao PY, Xia Y, Tao ZB, Li SY, Mao Z, Yang XP, Yao RQ, Du XH. Global Research Status of Multiple Organ Dysfunction Syndrome During 2001-2021: A 20-Year Bibliometric Analysis. Front Med (Lausanne) 2022; 9:814381. [PMID: 35308515 PMCID: PMC8931214 DOI: 10.3389/fmed.2022.814381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 02/11/2022] [Indexed: 12/29/2022] Open
Abstract
Background Multiple Organ Dysfunction Syndrome (MODS) is a major cause of high morbidity and mortality among patients in intensive care units (ICU). Although numerous basic and clinical researches on MODS have been conducted, there is still a long way to go to prevent patients from entering this stage. To our knowledge, no bibliometric analyses of MODS have been reported, this study, therefore, was conducted to reveal MODS research status and trends during 2001–2021. Methods All relevant literature covering MODS during 2001–2021 were extracted from Web of Science. An online analysis platform of literature metrology was used to analyze the publication trends. VOSviewer software was used to collect and analyze the keywords and research hotspots related to MODS. Results As of July 31, 2021, a total of 994 MODS-related articles from 2001 to 2021 were identified. The United States accounted for the largest number of publications (31.1%), followed by China and Germany, with 186 and 75 publications, respectively. Among all the institutions, the University of Pittsburgh published the most papers related to MODS (21). Critical Care Medicine published the most papers in this field (106). Professor Moore EE, who had the most citation frequency (1847), made great achievements in MODS research. Moreover, analysis of the keywords identified three MODS research hotspot clusters: “mechanism-related research,” “clinical research,” and “diagnostic research.” Conclusions The United States maintained a top position worldwide and made the most outstanding contribution in the MODS field. In terms of publication, China was next only to the United States, but there was a disproportion between the quantity of publications and citation frequency. The institution University of Pittsburgh and journal Critical Care Medicine represent the highest level of research in this field. During the 20 years from 2001 to 2021, basic MODS research has been in-depth yet progressed relatively slowly recently, but the outbreak of COVID-19 has to some extent set off an upsurge of clinical research in MODS field.
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Affiliation(s)
- Peng-Yue Zhao
- Department of General Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China.,Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Yun Xia
- Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zheng-Bo Tao
- Department of Orthopedics, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Song-Yan Li
- Department of General Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhi Mao
- Department of Critical Care Medicine, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xing-Peng Yang
- Department of General Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ren-Qi Yao
- Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China.,Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Xiao-Hui Du
- Department of General Surgery, First Medical Center of Chinese PLA General Hospital, Beijing, China
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Can O, Otunctemur A. Impact of coronavirus disease on the management of lower urinary tract symptoms and voiding dysfunction. Curr Opin Urol 2022; 32:141-145. [PMID: 34930886 PMCID: PMC8815648 DOI: 10.1097/mou.0000000000000955] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Coronavirus disease (COVID-19) has caused a crisis in the entire healthcare system since its emergence. The urgency and priority of various diseases have impacted the medical and surgical treatment in this period. We aim to review the impact of COVID-19 on lower urinary tract symptoms (LUTS) and management. RECENT FINDINGS There may be a relationship between COVID-19 and de novo or increased LUTS. Patients with LUTS should also be evaluated for COVID-19. Management of diseases has varied during the COVID-19 due to the density of the pandemic. Virtual consultations can mitigate patients who are postponed or cancelled, such as patients with LUTS. Patients suffering voiding dysfunction may manage with oral medications such as alpha blocker and 5-alpha reductase inhibitor via telemedicine. Minimally invasive procedures with a low risk of complications and a short hospitalization time should be considered in complicated cases such as the inability to catheterize. SUMMARY Telemedicine should be implemented on managements of noncomplicated LUTS and voiding dysfunction. Each centre can schedule its LUTS management approach according to the density of pandemic. Virtual consultations need to be developed to compete with face-to-face consultations.
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Affiliation(s)
- Osman Can
- Basaksehir Cam and Sakura City Hospital
| | - Alper Otunctemur
- Prof. Dr Cemil Tascioglu City Hospital, Department of Urology, Istanbul, Turkey
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Tews H, Kandulski A, Schmid S, Peschel G, Gülow K, Schlosser S, Schirner S, Stroszczynski C, Müller M, Jung E. Contrast enhanced ultrasonography (CEUS) a novel tool to detect intestinal epithelial barrier dysfunction in severe COVID-19 disease. Clin Hemorheol Microcirc 2022; 81:177-190. [DOI: 10.3233/ch-221407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Ten patients with confirmed COVID-19 disease were studied. Nine patients required intensive care treatment, among them four needed extracorporeal membrane oxygenation (ECMO). Contrast enhanced ultrasonography (CEUS) was performed by one experienced investigator as a bolus injection of up to 2.4 ml of sulphur hexafluoride microbubbles via a central venous catheter. B-Mode evaluation and strain elastography showed mural edema of the small bowel with a thickness of up to 10 mm in all patients. We applied color coded Doppler sonography (CCDS) and power mode with flow-adapted parameters and early, dynamic capillary arterial contrast enhancement of bowel wall structures <10 s to assess perfusion of the small bowel. In all patients, reactive hyperemia was seen in the entire small bowel. In a subgroup of seven patients microbubbles translocated into the intestinal lumen. Thus, high-grade intestinal barrier disruption secondary to SARSCoV-2 infection can be postulated in these patients. This is the first description of perfusion changes and a disruption of the small bowel epithelial barrier in COVID-19 Patients using contrast ultrasonography and elastography.
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Affiliation(s)
- H.C. Tews
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - A. Kandulski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - S. Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - G. Peschel
- Departement of Internal Medicine, Fürstenfeldbruck, Germany
| | - K. Gülow
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | | | - S. Schirner
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - C. Stroszczynski
- Institute of Diagnostic Radiology, University Hospital, Regensburg, Germany
| | - M. Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital, Regensburg, Germany
| | - E.M. Jung
- Institute of Diagnostic Radiology, University Hospital, Regensburg, Germany
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Steffen BT, Pankow JS, Lutsey PL, Demmer RT, Misialek JR, Guan W, Cowan LT, Coresh J, Norby FL, Tang W. Proteomic profiling identifies novel proteins for genetic risk of severe COVID-19: the Atherosclerosis Risk in Communities Study. Hum Mol Genet 2022; 31:2452-2461. [PMID: 35212764 PMCID: PMC9307314 DOI: 10.1093/hmg/ddac024] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 01/10/2022] [Accepted: 01/19/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Genome-wide association studies have identified six genetic variants associated with severe COVID-19, yet the mechanisms through which they may affect disease remains unclear. We investigated proteomic signatures related to COVID-19 risk variants rs657152 (ABO), rs10735079 (OAS1/OAS2/OAS3), rs2109069 (DPP9), rs74956615 (TYK2), rs2236757 (IFNAR2) and rs11385942 (SLC6A20/LZTFL1/CCR9/FYCO1/CXCR6/XCR1) as well as their corresponding downstream pathways that may promote severe COVID-19 in risk allele carriers and their potential relevancies to other infection outcomes. METHODS A DNA aptamer-based array measured 4870 plasma proteins among 11 471 participants. Linear regression estimated associations between the COVID-19 risk variants and proteins with correction for multiple comparisons, and canonical pathway analysis was conducted. Cox regression assessed associations between proteins identified in the main analysis and risk of incident hospitalized respiratory infections (2570 events) over a 20.7-year follow-up. RESULTS The ABO variant rs657152 was associated with 84 proteins in 7241 white participants with 24 replicated in 1671 Black participants. The TYK2 variant rs74956615 was associated with ICAM-1 and -5 in white participants with ICAM-5 replicated in Black participants. Of the 84 proteins identified in the main analysis, seven were significantly associated with incident hospitalized respiratory infections including Ephrin type-A receptor 4 (hazard ratio (HR): 0.87; P = 2.3 × 10-11) and von Willebrand factor type A (HR: 1.17; P = 1.6x10-13). CONCLUSIONS Novel proteomics signatures and pathways for COVID-19-related risk variants TYK2 and ABO were identified. A subset of these proteins predicted greater risk of incident hospitalized pneumonia and respiratory infections. Further studies to examine these proteins in COVID-19 patients are warranted.
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Affiliation(s)
- Brian T Steffen
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - James S Pankow
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Pamela L Lutsey
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Ryan T Demmer
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA,Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
| | - Jeffrey R Misialek
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Weihua Guan
- Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA
| | - Logan T Cowan
- Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Jiann Ping-Hsu College of Public Health, Statesboro, GA 30458, USA
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA
| | - Faye L Norby
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA,Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Health System, Los Angeles 90048, CA
| | - Weihong Tang
- To whom correspondence should be addressed: Division of Epidemiology and Community Health, University of Minnesota, 1300 S. 2nd St., Suite 300, Minneapolis, MN 55454, USA. Tel: 6 126269140;
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Zou Q, Liu C, Hu N, Wang W, Wang H. miR-126 ameliorates multiple organ dysfunction in septic rats by regulating the differentiation of Th17/Treg. Mol Biol Rep 2022; 49:2985-2998. [PMID: 35122598 PMCID: PMC8817156 DOI: 10.1007/s11033-022-07121-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 01/04/2022] [Indexed: 10/25/2022]
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Andonovic M, Traynor JP, Shaw M, Sim MA, Mark PB, Puxty KA. Short- and long-term outcomes of intensive care patients with acute kidney disease. EClinicalMedicine 2022; 44:101291. [PMID: 35198917 PMCID: PMC8850318 DOI: 10.1016/j.eclinm.2022.101291] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 01/18/2022] [Accepted: 01/20/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Acute kidney disease (AKD) is a proposed definition for acute kidney injury (AKI) lasting 7 days or longer. Little has been reported regarding characteristics of patients with AKD and their short- and long-term outcomes. We describe the epidemiology and risk factors for AKD and outcomes following AKD. METHODS This retrospective observational cohort study identified patients aged 16 or older admitted to the Glasgow Royal Infirmary and Queen Elizabeth University Hospital intensive care units (ICUs) in Scotland between 1st July 2015 and 30th June 2018. Baseline serum creatinine and subsequent values were used to identify patients with de-novo kidney injury (DNKI). Patients with recovery prior to day 7 were classified as AKI; recovery at day 7 or beyond was classified as AKD. Outcomes were in-hospital and long-term mortality, and proportion of major adverse kidney events (MAKEs). Multivariable logistic regression was used to identify risk factors for AKD. A Cox proportional hazards model was used to identify factors associated with long-term outcomes. FINDINGS Of the 5,334 patients admitted to ICU who were assessed for DNKI, 1,620 (30·4%) suffered DNKI and of these, 403 (24·9%) met AKD criteria; 984 (60·7%) were male and the median age was 60·0 (IQR=48·0-72·0). Male sex, sepsis and lower baseline estimated glomerular filtration rate (eGFR) were associated with development of AKD. In-ICU (16·1%vs6·2%) and in-hospital (26·1%vs11·6%) mortality rates were significantly higher in AKD patients than AKI patients. Long-term survival was not different for AKD patients (HR=1·16; p-value=0·261) but AKD was associated with subsequent MAKEs (OR=1·25). INTERPRETATION One in four ICU patients with DNKI met AKD criteria. These patients had an increased risk of short-term mortality and long-term MAKEs. Whilst the trend for long-term survival was lower, this was not significantly different from shorter-term AKI patients. Patients with AKD during their ICU stay should be identified to initiate interventions to reduce risk of future MAKEs. FUNDING No funding was associated with this study.
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Affiliation(s)
- Mark Andonovic
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
- Corresponding author.
| | - Jamie P. Traynor
- Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom
| | - Martin Shaw
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
| | - Malcolm A.B. Sim
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
- Department of Intensive Care, Queen Elizabeth University Hospital, United Kingdom
| | - Patrick B. Mark
- Department of Nephrology, Queen Elizabeth University Hospital, United Kingdom
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom
| | - Kathryn A. Puxty
- Academic Unit of Anaesthesia, Pain and Critical Care, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
- Department of Intensive Care Medicine, Glasgow Royal Infirmary, United Kingdom
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Dai Q, Xie D, Zhang C, Zhu L, Xu Y, Li K, Hao W, Yin H. Osthole Blocks HMGB1 Release From the Nucleus and Confers Protective Effects Against Renal Ischemia-Reperfusion Injury. Front Physiol 2022; 12:735425. [PMID: 35002751 PMCID: PMC8727455 DOI: 10.3389/fphys.2021.735425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 10/20/2021] [Indexed: 11/13/2022] Open
Abstract
Renal ischemia-reperfusion (IR) is one of the main causes of renal injury. In severe cases with serious consequences, IR-related renal damage progresses rapidly and can even lead to acute renal failure. Its clinical treatment is currently difficult. According to various studies at home and abroad, HMGB1 is released from the nucleus into the cytoplasm or extracellular space by damaged parenchymal cells during ischemia and hypoxia, and this plays an important role in the initiation of reperfusion injury as an early inflammatory factor and is closely related to the occurrence and development of renal diseases. In recent years, the protective effect of osthole on IR of tissues and organs has been a key topic among clinical researchers. Osthole can inhibit the inflammatory response, reduce cell apoptosis the progression, and improve the prognosis of IR, thus protecting the kidney. During the development of renal IR, finding a mechanism through which the osthole blocks the release of HMGB1 from the nucleus would be helpful in detecting targets for clinical treatment.
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Affiliation(s)
- Qing Dai
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China.,North Sichuan Medical College, Nanchong, China
| | - Deqiong Xie
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Chenli Zhang
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Lei Zhu
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Ying Xu
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Kui Li
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Wen Hao
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
| | - Hefei Yin
- Department of Nephrology, The Second People's Hospital of Yibin, Yibin, China
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Kaur H, Ghorai SM. Role of Cytokines as Immunomodulators. IMMUNOMODULATORS AND HUMAN HEALTH 2022:371-414. [DOI: 10.1007/978-981-16-6379-6_13] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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50
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Xie TA, He ZJ, Liang C, Dong HN, Zhou J, Fan SJ, Guo XG. An integrative bioinformatics analysis for identifying hub genes associated with infection of lung samples in patients infected with SARS-CoV-2. Eur J Med Res 2021; 26:146. [PMID: 34920753 PMCID: PMC8677925 DOI: 10.1186/s40001-021-00609-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 11/14/2021] [Indexed: 12/22/2022] Open
Abstract
Background At the end of 2019, the world witnessed the emergence and ravages of a viral infection induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Also known as the coronavirus disease 2019 (COVID-19), it has been identified as a public health emergency of international concern (PHEIC) by the World Health Organization (WHO) because of its severity. Methods The gene data of 51 samples were extracted from the GSE150316 and GSE147507 data set and then processed by means of the programming language R, through which the differentially expressed genes (DEGs) that meet the standards were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the selected DEGs to understand the functions and approaches of DEGs. The online tool STRING was employed to construct a protein–protein interaction (PPI) network of DEGs and, in turn, to identify hub genes. Results A total of 52 intersection genes were obtained through DEG identification. Through the GO analysis, we realized that the biological processes (BPs) that have the deepest impact on the human body after SARS-CoV-2 infection are various immune responses. By using STRING to construct a PPI network, 10 hub genes were identified, including IFIH1, DDX58, ISG15, EGR1, OASL, SAMD9, SAMD9L, XAF1, IFITM1, and TNFSF10. Conclusion The results of this study will hopefully provide guidance for future studies on the pathophysiological mechanism of SARS-CoV-2 infection. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-021-00609-4.
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