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Ortiz-Prado E, Izquierdo-Condoy JS, Vasconez-Gonzalez J, López-Cortés A, Salazar-Santoliva C, Vargas Michay AR, Vélez-Paéz JL, Unigarro L. From pandemic onset to present: five years of insights into ARDS caused by COVID-19. Expert Rev Respir Med 2025:1-20. [PMID: 40372206 DOI: 10.1080/17476348.2025.2507207] [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: 02/28/2025] [Revised: 04/28/2025] [Accepted: 05/13/2025] [Indexed: 05/16/2025]
Abstract
INTRODUCTION COVID-19-associated acute respiratory distress syndrome (ARDS) has challenged healthcare systems, initially resembling classical ARDS but later recognized as distinct. Unique features such as endothelial injury, microthrombosis, and dysregulated inflammation influenced treatment efficacy. Understanding its evolution is key to optimizing therapy and improving outcomes. AREAS COVERED This review synthesizes current evidence on COVID-19-associated ARDS, covering epidemiology, pathophysiology, clinical phenotypes, and treatments. It explores the shift from L and H phenotypes to a refined disease model and highlights key therapies, including corticosteroids, immunomodulators, prone positioning, ECMO, and vaccination's impact on severity and ARDS incidence. EXPERT OPINION At the onset of the COVID-19 pandemic in December 2019, uncertainty was overwhelming. Early clinical guidelines relied on case reports and small case series, offering only preliminary insights into disease progression and management. Despite the initial chaos, the scientific community launched an unprecedented research effort, with over 11,000 clinical trials registered on ClinicalTrials.gov investigating COVID-19 treatments. Several evidence-based strategies emerged as gold standards for managing COVID-19-associated acute respiratory distress syndrome, surpassing prior approaches. The pandemic exposed vulnerabilities in global healthcare, reshaped modern medicine, accelerated innovation, and reinforced the essential role of evidence-based practice in critical care and public health policy.
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Affiliation(s)
- Esteban Ortiz-Prado
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Juan S Izquierdo-Condoy
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Jorge Vasconez-Gonzalez
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | - Andrés López-Cortés
- Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador
| | - Camila Salazar-Santoliva
- One Health Research Group, Faculty of Health Science, Universidad de Las Americas, Quito, Ecuador
| | | | - Jorge Luis Vélez-Paéz
- Universidad Central del Ecuador, Facultad de Ciencias Médicas, Escuela de Medicina, Quito, Ecuador
- Hospital Pablo Arturo Suárez, Unidad de Terapia Intensiva, Centro de Investigación Clínica, Quito, Ecuador
| | - Luis Unigarro
- Department of Intensive Care Unit, Oncologic Hospital SOLCA, Quito, Ecuador
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Vargas-Ángeles CA, Trujillo-Cirilo L, Sierra-Mondragón E, Rangel-Corona R, Weiss-Steider B. Cationic liposomes encapsulating IL-2 selectively induce apoptosis and significantly reduce the secretion of cytokines on M1-murine polarized macrophages. Cytokine 2025; 189:156903. [PMID: 40023103 DOI: 10.1016/j.cyto.2025.156903] [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: 10/31/2024] [Revised: 02/13/2025] [Accepted: 02/20/2025] [Indexed: 03/04/2025]
Abstract
Inflammatory diseases pose a global challenge due to the critical role of macrophages in their pathogenesis. This study evaluated the effects of cationic liposomes encapsulating IL-2 (LIP-IL-2) on murine peritoneal macrophages (MP) polarized towards M1 and M2 phenotypes. M1 MP (CD86+), which overexpressed IL-2Rα and CD14 receptors, underwent apoptosis following LIP-IL-2 treatment, whereas M2 MP (CD206+) were unaffected. Furthermore, LIP-IL-2 significantly reduced the secretion of pro-inflammatory cytokines, including IL-6, TNF-α, IFN-γ, and IL-12, exclusively in M1 macrophages. These findings suggest that LIP-IL-2 could serve as a promising therapeutic tool for chronic inflammatory diseases by selectively inducing apoptosis in pro-inflammatory M1 macrophages without affecting M2 ones, opening avenues for targeted therapies in diseases where chronic macrophage-mediated inflammation is a key factor.
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Affiliation(s)
- C A Vargas-Ángeles
- Laboratory of Cellular Oncology, Cell Differentiation and Cancer Unit, L-4 PB, FES Zaragoza, National Autonomous University of Mexico, Av. Guelatao No 66 Col. Ejercito de Oriente, Iztapalapa, CP 09230, México City, Mexico; Graduate Program in Biological Sciences, National Autonomous University of Mexico, Mexico City, Mexico
| | - L Trujillo-Cirilo
- Laboratory of Cellular Oncology, Cell Differentiation and Cancer Unit, L-4 PB, FES Zaragoza, National Autonomous University of Mexico, Av. Guelatao No 66 Col. Ejercito de Oriente, Iztapalapa, CP 09230, México City, Mexico
| | - E Sierra-Mondragón
- Laboratory of Cellular Oncology, Cell Differentiation and Cancer Unit, L-4 PB, FES Zaragoza, National Autonomous University of Mexico, Av. Guelatao No 66 Col. Ejercito de Oriente, Iztapalapa, CP 09230, México City, Mexico
| | - R Rangel-Corona
- Laboratory of Cellular Oncology, Cell Differentiation and Cancer Unit, L-4 PB, FES Zaragoza, National Autonomous University of Mexico, Av. Guelatao No 66 Col. Ejercito de Oriente, Iztapalapa, CP 09230, México City, Mexico.
| | - B Weiss-Steider
- Laboratory of Cellular Oncology, Cell Differentiation and Cancer Unit, L-4 PB, FES Zaragoza, National Autonomous University of Mexico, Av. Guelatao No 66 Col. Ejercito de Oriente, Iztapalapa, CP 09230, México City, Mexico
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Sen’kova AV, Savin IA, Chernolovskaya EL, Davydova AS, Meschaninova MI, Bishani A, Vorobyeva MA, Zenkova MA. LPS-Induced Acute Lung Injury: Analysis of the Development and Suppression by the TNF-α-Targeting Aptamer. Acta Naturae 2024; 16:61-71. [PMID: 39188267 PMCID: PMC11345095 DOI: 10.32607/actanaturae.27393] [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: 03/22/2024] [Accepted: 04/15/2024] [Indexed: 08/28/2024] Open
Abstract
Acute lung injury (ALI) is a specific form of lung inflammation characterized by diffuse alveolar damage, noncardiogenic pulmonary edema, as well as a pulmonary and systemic inflammation. The pathogenesis of ALI involves a cascade inflammatory response accompanied by an increase in the local and systemic levels of proinflammatory cytokines and chemokines. The development of molecular tools targeting key components of cytokine signaling appears to be a promising approach in ALI treatment. The development of lipopolysaccharide (LPS)-induced ALI, as well as the feasibility of suppressing it by an aptamer targeting the proinflammatory cytokine TNF-α, was studied in a mouse model. The TNF-α level was shown to increase significantly and remain steadily high during the development of ALI. LPS-induced morphological signs of inflammation in the respiratory system become most pronounced 24 h after induction. Intranasal administration of TNF-α-targeting aptamers conjugated with polyethylene glycol (PEG-aptTNF-α) to mice with ALI reduced the intensity of inflammatory changes in lung tissue. Assessment of the levels of potential TNF-α target genes (Usp18, Traf1, and Tnfaip3) showed that their expression levels in the lungs increase during ALI development, while declining after the application of PEG-aptTNF-α. Therefore, topical use of TNF-α- targeting aptamers may be an efficient tool for treating ALI and other inflammatory lung diseases.
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Affiliation(s)
- A. V. Sen’kova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - I. A. Savin
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - E. L. Chernolovskaya
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - A. S. Davydova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - M. I. Meschaninova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - A. Bishani
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - M. A. Vorobyeva
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
| | - M. A. Zenkova
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russian Federation
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4
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Park JB. Methyl 2-[3-(4-hydroxyphenyl)prop-2-enoylamino]-3-phenylpropanoate Is a Potent Cell-Permeable Anti-Cytokine Compound To Inhibit Inflammatory Cytokines in Monocyte/Macrophage-Like Cells. J Pharmacol Exp Ther 2024; 388:181-189. [PMID: 37918857 PMCID: PMC10765419 DOI: 10.1124/jpet.123.001830] [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: 07/17/2023] [Revised: 09/15/2023] [Accepted: 10/02/2023] [Indexed: 11/04/2023] Open
Abstract
Cytokines are signaling molecules involved in inflammation process. Interleukin (IL)-6 is one of pivotal inflammatory cytokines associated with many human diseases. Therefore, there are on-going efforts to find a therapeutic to inhibit IL-6 and other cytokines. Methyl 2-[3-(4-hydroxyphenyl)prop-2-enoylamino]-3-phenylpropanoate (MHPAP) is a phenolic amide ester, transported better than its non-ester form (NEF) in monocyte/macrophage-like cells. However, there is no information about the effects of their cell permeability on cytokines. Therefore, the effects of MHPAP and NEF on cytokines were investigated in lipopolysaccharide (LPS)-stimulated THP-1 and human peripheral blood mononuclear cells (PBMCs). In the THP-1 cells, MHPAP significantly inhibited IL-6, IL-1beta, IL-8, and tumor necrosis factor (TNF)-alpha (P < 0.05), but NEF showed no effects. MHPAP also inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 phosphorylation in the THP-1 cells (P < 0.05), without significant effects on c-FOS, ATF-2, and JUN phosphorylations. Because NF-κB p65 is phosphorylated by IκB kinase (IKK), in silico analysis was performed on IKK. MHPAP was found to bind to IKK better than an IKK inhibitor ((E)-2-fluoro-4'-methoxystilbene). Furthermore, MHPAP inhibited the luminescence increased in the LPS-stimulated NF-κB-Luc2 THP-1 cells. As anticipated, MHPAP was also found to inhibit IL-6, IL-1beta, IL-8, and TNF-alpha significantly in LPS-stimulated PBMCs (P < 0.05). Especially, MHPAP inhibited IL-6 and IL-1beta with an IC50 of 0.85 and 0.87 µM, better than IL-8 (1.58 µM) and TNF-alpha (1.22 µM) in the cells. Altogether, the data suggest that cell permeability may have a significant impact on MHPAP's ability to inhibit cytokines and MHPAP may be used as a potent cell-permeable compound to inhibit inflammatory cytokines in monocyte/macrophage-like cells. SIGNIFICANCE STATEMENT: Potential effects of MHPAP and NEF on inflammatory cytokines (IL-6, IL-8, IL-1beta, and TNF-alpha) were investigated in LPS-stimulated THP-1 and PBMCs. Cell transport had a great impact on cytokine inhibition in the cells. MHPAP was also found to inhibit NF-κB pathway, which was supported by in silico and NF-κB reporter (Luc)-THP-1 data. Also, in LPS-stimulated PBMCs, MHPAP significantly inhibited IL-6, IL-1beta, IL-8, and TNF-alpha, suggesting that MHPAP may be a potent cell-permeable compound to inhibit inflammatory cytokines in monocyte/macrophage-like cells.
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Affiliation(s)
- Jae B Park
- Diet, Genomics, and Immunology Laboratory, US Department of Agriculture, Beltsville, Maryland
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Mia ME, Howlader M, Akter F, Hossain MM. Preclinical and Clinical Investigations of Potential Drugs and Vaccines for COVID-19 Therapy: A Comprehensive Review With Recent Update. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2024; 17:2632010X241263054. [PMID: 39070952 PMCID: PMC11282570 DOI: 10.1177/2632010x241263054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 06/03/2024] [Indexed: 07/30/2024]
Abstract
The COVID-19 pandemic-led worldwide healthcare crisis necessitates prompt societal, ecological, and medical efforts to stop or reduce the rising number of fatalities. Numerous mRNA based vaccines and vaccines for viral vectors have been licensed for use in emergencies which showed 90% to 95% efficacy in preventing SARS-CoV-2 infection. However, safety issues, vaccine reluctance, and skepticism remain major concerns for making mass vaccination a successful approach to treat COVID-19. Hence, alternative therapeutics is needed for eradicating the global burden of COVID-19 from developed and low-resource countries. Repurposing current medications and drug candidates could be a more viable option for treating SARS-CoV-2 as these therapies have previously passed a number of significant checkpoints for drug development and patient care. Besides vaccines, this review focused on the potential usage of alternative therapeutic agents including antiviral, antiparasitic, and antibacterial drugs, protease inhibitors, neuraminidase inhibitors, and monoclonal antibodies that are currently undergoing preclinical and clinical investigations to assess their effectiveness and safety in the treatment of COVID-19. Among the repurposed drugs, remdesivir is considered as the most promising agent, while favipiravir, molnupiravir, paxlovid, and lopinavir/ritonavir exhibited improved therapeutic effects in terms of elimination of viruses. However, the outcomes of treatment with oseltamivir, umifenovir, disulfiram, teicoplanin, and ivermectin were not significant. It is noteworthy that combining multiple drugs as therapy showcases impressive effectiveness in managing individuals with COVID-19. Tocilizumab is presently employed for the treatment of patients who exhibit COVID-19-related pneumonia. Numerous antiviral drugs such as galidesivir, griffithsin, and thapsigargin are under clinical trials which could be promising for treating COVID-19 individuals with severe symptoms. Supportive treatment for patients of COVID-19 may involve the use of corticosteroids, convalescent plasma, stem cells, pooled antibodies, vitamins, and natural substances. This study provides an updated progress in SARS-CoV-2 medications and a crucial guide for inventing novel interventions against COVID-19.
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Affiliation(s)
- Md. Easin Mia
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh
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Ali GK, Algethami FK, Omer KM. Gold single atom-based aptananozyme as an ultrasensitive and selective colorimetric probe for detection of thrombin and C-reactive protein. Mikrochim Acta 2023; 191:59. [PMID: 38153560 DOI: 10.1007/s00604-023-06147-6] [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: 09/05/2023] [Accepted: 12/07/2023] [Indexed: 12/29/2023]
Abstract
An ultra-efficient biocatalytic peroxidase-like Au-based single-atom nanozyme (Au-SAzymes) has been synthesized from isolated Au atoms on black nitrogen doped carbon (Au-N-C) using a simple complexation-adsorption-pyrolysis method. The atomic structure of AuN4 centers in black carbon was revealed by combined high-resolution transmission electron microscopy/high-angle annular dark-field scanning transmission electron microscopy. The Au-SAzymes showed a remarkable peroxidase activity with 1.7 nM as Michaelis-Menten constant, higher than most previously reported SAzyme activity. Density functional theory and Monte Carlo calculations revealed the adsorption of H2O2 on AuN4 with formation of OH* and O*. Molecular recognition was greatly enhanced via label-free integration of thiol-terminal aptamers on the surface of single Au atoms (Aptamer/Au-SAzyme) to design off-on ultrasensitive aptananozyme-based sensor for detecting thrombin and CRP with 550 pM and 500 pg mL-1 limits of detection, respectively. The Aptamer/Au-SAzyme showed satisfactory accuracy and precision when applied to the serum and plasma of COVID-19 patients. Due to the maximum Au atom utilization, approximately 3636 samples can be run per 1 mg of gold, highlighting the commercialization potential of the developed Aptamer/Au-SAzyme approach.
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Affiliation(s)
- Gona K Ali
- Department of Chemistry, College of Science, University of Sulaimani, Slemani City, 46002, Kurdistan Region, Iraq
| | - Faisal K Algethami
- Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), 11623, Riyadh, Saudi Arabia
| | - Khalid M Omer
- Department of Chemistry, College of Science, University of Sulaimani, Slemani City, 46002, Kurdistan Region, Iraq.
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Velayutham M, Poncelet M, Perini JA, Kupec JT, Dietz MJ, Driesschaert B, Khramtsov VV. EPR Viscometric Measurements Using a 13C-Labeled Triarylmethyl Radical in Protein-based Biotherapeutics and Human Synovial Fluids. APPLIED MAGNETIC RESONANCE 2023; 54:779-791. [PMID: 38707765 PMCID: PMC11068027 DOI: 10.1007/s00723-023-01556-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/22/2023] [Accepted: 06/22/2023] [Indexed: 05/07/2024]
Abstract
The viscosity measurements are of clinical significance for evaluation of the potential pathological conditions of biological lubricants such as synovial fluids of joints, and for formulation and characterization of peptide- and protein-based biotherapeutics. Due to inherent potential therapeutic activity, protein drugs have proven to be one of the most efficient therapeutic agents in treatment of several life-threatening disorders, such as diabetes and autoimmune diseases. However, home-use applications for treating chronic inflammatory diseases, such as diabetes and rheumatoid arthritis, necessitate the development of high-concentration insulin and monoclonal antibodies formulations for patient self-administration. High protein concentrations can affect viscosity of the corresponding drug solutions complicating their manufacture and administration. The measurements of the viscosity of new insulin analogs and monoclonal antibodies solutions under development is of practical importance to avoid unwanted highly viscous, and therefore, painful for injection drug formulations. Recently, we have demonstrated capability of the electron paramagnetic resonance (EPR) viscometry using viscosity-sensitive 13C-labeled trityl spin probe (13C1-dFT) to report the viscosity of human blood, and interstitial fluids measured in various organs in mice ex-vivo and in anesthetized mice, in vivo. In the present work, we demonstrate utility of the EPR viscometry using 13C1-dFT to measure microviscosity of commercial insulin samples, antibodies solution, and human synovial fluids using small microliter volume samples (5-50 μL). This viscometry analysis approach provides useful tool to control formulations and administration of new biopharmaceuticals, and for evaluation of the state of synovial fluids of importance for clinical applications.
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Affiliation(s)
- Murugesan Velayutham
- In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center
- Department of Biochemistry and Molecular Medicine
| | - Martin Poncelet
- In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center
- Department of Pharmaceutical Sciences
| | | | | | | | - Benoit Driesschaert
- In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center
- Department of Pharmaceutical Sciences
- C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA
| | - Valery V. Khramtsov
- In Vivo Multifunctional Magnetic Resonance center, Robert C. Byrd Health Sciences Center
- Department of Biochemistry and Molecular Medicine
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Zou L, Dang W, Tao Y, Zhao H, Yang B, Xu X, Li Y. THE IL-33/ST2 AXIS PROMOTES ACUTE RESPIRATORY DISTRESS SYNDROME BY NATURAL KILLER T CELLS. Shock 2023; 59:902-911. [PMID: 36870074 PMCID: PMC10227934 DOI: 10.1097/shk.0000000000002114] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 02/24/2023] [Indexed: 03/06/2023]
Abstract
ABSTRACT Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled inflammation, which manifests as leukocyte infiltration and lung injury. However, the molecules that initiate this infiltration remain incompletely understood. We evaluated the effect of the nuclear alarmin IL-33 on lung damage and the immune response in LPS-induced lung injury. We established a LPS-induced lung injury mouse model. We used genetically engineered mice to investigate the relationship among the IL-33/ST2 axis, NKT cells, and ARDS. We found that IL-33 was localized to the nucleus in alveolar epithelial cells, from which it was released 1 h after ARDS induction in wild-type (WT) mice. Mice lacking IL-33 (IL-33 - / - ) or ST2 (ST2 - / - ) exhibited reduced neutrophil infiltration, alveolar capillary leakage, and lung injury in ARDS compared with WT mice. This protection was associated with decreased lung recruitment and activation of invariant nature killer (iNKT) cells and activation of traditional T cells. Then, we validated that iNKT cells were deleterious in ARDS in CD1d - / - and Vα14Τg mice. Compared with WT mice, Vα14Τg mice exhibited increased lung injury in ARDS, and the CD1d - / - mice showed outcomes opposite those of the Vα14Τg mice. Furthermore, we administered a neutralizing anti-ST2 antibody to LPS-treated WT and Vα14Τg mice 1 h before LPS administration. We found that IL-33 promoted inflammation through NKT cells in ARDS. In summary, our results demonstrated that the IL-33/ST2 axis promotes the early uncontrolled inflammatory response in ARDS by activating and recruiting iNKT cells. Therefore, IL-33 and NKT cells may be therapeutic target molecules and immune cells, respectively, in early ARDS cytokine storms.
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Affiliation(s)
- Lijuan Zou
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenpei Dang
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiming Tao
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Zhao
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Yang
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinxin Xu
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yongsheng Li
- Department of Intensive Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- The Emergency Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Majumder R, Ghosh S, Singh MK, Das A, Roy Chowdhury S, Saha A, Saha RP. Revisiting the COVID-19 Pandemic: An Insight into Long-Term Post-COVID Complications and Repurposing of Drugs. COVID 2023; 3:494-519. [DOI: 10.3390/covid3040037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
SARS-CoV-2 is a highly contagious and dangerous coronavirus that has been spreading around the world since late December 2019. Severe COVID-19 has been observed to induce severe damage to the alveoli, and the slow loss of lung function led to the deaths of many patients. Scientists from all over the world are now saying that SARS-CoV-2 can spread through the air, which is a very frightening prospect for humans. Many scientists thought that this virus would evolve during the first wave of the pandemic and that the second wave of reinfection with the coronavirus would also be very dangerous. In late 2020 and early 2021, researchers found different genetic versions of the SARS-CoV-2 virus in many places around the world. Patients with different types of viruses had different symptoms. It is now evident from numerous case studies that many COVID-19 patients who are released from nursing homes or hospitals are more prone to developing multi-organ dysfunction than the general population. Understanding the pathophysiology of COVID-19 and its impact on various organ systems is crucial for developing effective treatment strategies and managing long-term health consequences. The case studies highlighted in this review provide valuable insights into the ongoing health concerns of individuals affected by COVID-19.
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Affiliation(s)
- Rajib Majumder
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Sanmitra Ghosh
- Department of Biological Sciences, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Manoj K. Singh
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Arpita Das
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Swagata Roy Chowdhury
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Abinit Saha
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
| | - Rudra P. Saha
- Department of Biotechnology, School of Life Science & Biotechnology, Adamas University, Kolkata 700126, India
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Umashankar A, Prakash P, Prabhu P. Delta Variant of Covid-19 and Hearing Loss. Indian J Otolaryngol Head Neck Surg 2023. [PMCID: PMC10054221 DOI: 10.1007/s12070-023-03724-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
The Coronavirus Disease of 2019 has now become one of the biggest pandemics of all time. Under the influence of ongoing mutations and widespread geographical expansions, several variants have been reported. Among those, the B.1.617.2 variant, most commonly known as the ‘Delta variant’ of the coronavirus disease – 19, was first reported in the state of Maharashtra of India in December 2020 and have currently been detected in over 43 countries across six continents around the globe. The B.1.617.2 variant of COVID 19 is a more treacherous variant than the alpha variant due to the increased replication leading to higher viral loads and increased transmission with minimal literature reporting about vaccines’ efficacy. In patients with the Alpha variant of COVID-19, hearing loss was an infrequent symptom seen, but on the other hand, the Delta variant happens to have a more frequent hearing loss as a symptom. The increased severity could be one of the reasons why hearing loss could be a typically seen symptom with high chances of occurrence of either a thrombosis, cross-reaction, labyrinthitis/neuritis, etc. and thus audiologists and otolaryngologists must be prepared for the post effect of the delta variant to evaluate and rehabilitate the individuals affected with hearing loss. The following article discusses the presence of hearing loss in individuals with delta variant of COVID 19 and the role of audiologists and otolaryngologists in hearing care.
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Affiliation(s)
| | - Praveen Prakash
- All India Institute of Speech and Hearing Mysuru, Mysore, India
| | - Prashanth Prabhu
- Department of Audiology, All India Institute of Speech and Hearing Mysuru, Naimisham Campus, Road No.3 TK Layout, Manasagangotri, 570006 Mysuru, Karnataka India
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Schmidt W, Pawlak-Buś K, Jóźwiak B, Leszczyński P. Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience. J Clin Med 2023; 12:jcm12062429. [PMID: 36983429 PMCID: PMC10051490 DOI: 10.3390/jcm12062429] [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: 02/19/2023] [Revised: 03/19/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.
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Affiliation(s)
- Wiktor Schmidt
- Department of Rheumatology, Systemic Connective Tissue Diseases and Immunotherapy of Rheumatic Diseases, J. Strus Municipal Hospital, 61-285 Poznan, Poland
- Department of Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland
- Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland
| | - Katarzyna Pawlak-Buś
- Department of Rheumatology, Systemic Connective Tissue Diseases and Immunotherapy of Rheumatic Diseases, J. Strus Municipal Hospital, 61-285 Poznan, Poland
- Department of Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland
| | - Barbara Jóźwiak
- Department of Rheumatology, Systemic Connective Tissue Diseases and Immunotherapy of Rheumatic Diseases, J. Strus Municipal Hospital, 61-285 Poznan, Poland
| | - Piotr Leszczyński
- Department of Rheumatology, Systemic Connective Tissue Diseases and Immunotherapy of Rheumatic Diseases, J. Strus Municipal Hospital, 61-285 Poznan, Poland
- Department of Internal Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland
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12
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Mezhibovsky E, Hoang SH, Szeto S, Roopchand DE. In silico analysis of dietary polyphenols and their gut microbial metabolites suggest inhibition of SARS-CoV-2 infection, replication, and host inflammatory mediators. J Biomol Struct Dyn 2023; 41:14339-14357. [PMID: 36803516 PMCID: PMC10439978 DOI: 10.1080/07391102.2023.2180669] [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: 08/09/2022] [Accepted: 02/09/2023] [Indexed: 02/22/2023]
Abstract
The outcome of SARS-CoV-2 infection ranges from asymptomatic to severe COVID-19 and death resulting from an exaggerated immune response termed cytokine storm. Epidemiological data have associated consumption of a high-quality plant-based diet with decreased incidence and severity of COVID-19. Dietary polyphenols and their microbial metabolites (MMs) have anti-viral and anti-inflammatory activities. Autodock Vina and Yasara were used in molecular docking and dynamics studies to investigate potential interactions of 7 parent polyphenols (PPs) and 11 MMs with the α- and Omicron variants of the SARS-CoV-2 spike glycoprotein (SGP), papain-like pro-tease (PLpro) and 3 chymotrypsin-like protease (3CLpro), as well as host inflammatory mediators including complement component 5a (C5a), C5a receptor (C5aR), and C-C chemokine receptor type 5 (CCR5). PPs and MMs interacted to varying degrees with residues on target viral and host inflammatory proteins showing potential as competitive inhibitors. Based on these in silico findings, PPs and MMs may inhibit SARS-CoV-2 infection, replication, and/or modulate host immunity in the gut or periphery. Such inhibition may explain why people that consume a high-quality plant-based diet have less incidence and severity of COVID-19.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Esther Mezhibovsky
- Department of Food Science, Rutgers University, NJ Institute for Food, Nutrition and Health (Rutgers Center for Lipid Research and Center for Nutrition, Microbiome, and Health), 61 Dudley Rd., New Brunswick, NJ 08901 USA
- Department of Nutritional Sciences Graduate Program, Rutgers University
| | - Skyler H. Hoang
- Department of Food Science, Rutgers University, NJ Institute for Food, Nutrition and Health (Rutgers Center for Lipid Research and Center for Nutrition, Microbiome, and Health), 61 Dudley Rd., New Brunswick, NJ 08901 USA
| | - Samantha Szeto
- Department of Food Science, Rutgers University, NJ Institute for Food, Nutrition and Health (Rutgers Center for Lipid Research and Center for Nutrition, Microbiome, and Health), 61 Dudley Rd., New Brunswick, NJ 08901 USA
| | - Diana E. Roopchand
- Department of Food Science, Rutgers University, NJ Institute for Food, Nutrition and Health (Rutgers Center for Lipid Research and Center for Nutrition, Microbiome, and Health), 61 Dudley Rd., New Brunswick, NJ 08901 USA
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13
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Zhao SW, Li YM, Li YL, Su C. Liver injury in COVID-19: Clinical features, potential mechanisms, risk factors and clinical treatments. World J Gastroenterol 2023; 29:241-256. [PMID: 36687127 PMCID: PMC9846943 DOI: 10.3748/wjg.v29.i2.241] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/11/2022] [Accepted: 12/08/2022] [Indexed: 01/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.
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Affiliation(s)
- Shu-Wu Zhao
- Department of Anesthesiology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Yi-Ming Li
- School of Basic Medical Science, Naval Medical University/Second Military University, Shanghai 200433, China
| | - Yi-Lin Li
- Department of Pathology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
| | - Chen Su
- Department of Anesthesiology and Pain, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, Hunan Province, China
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14
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Zhao J, Zhu J, Huang C, Zhu X, Zhu Z, Wu Q, Yuan R. Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis. Front Immunol 2022; 13:1035151. [PMID: 36405695 PMCID: PMC9670819 DOI: 10.3389/fimmu.2022.1035151] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 10/17/2022] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND Since the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics. METHODS Publications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis. RESULTS 1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: "Delta/Omicron variants", "cytokine storm", "neutralization/neutralizing antibody", "T cell", "BNT162b2", "mRNA vaccine", "vaccine effectiveness/safety", and "long COVID". CONCLUSION This study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.
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Affiliation(s)
- Jiefeng Zhao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jinfeng Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Chao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xiaojian Zhu
- Center for Digestive Disease, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhengming Zhu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Qinrong Wu
- Department of General Surgery, Yingtan City People’s Hospital, Yingtan, Jiangxi, China
| | - Rongfa Yuan
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Marques P, Fernandez-Presa L, Carretero A, Gómez-Cabrera MC, Viña J, Signes-Costa J, Sanz MJ. The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019—Potential new admission biomarkers to predict coronavirus disease 2019 worsening. Front Med (Lausanne) 2022; 9:871714. [PMID: 36035415 PMCID: PMC9402930 DOI: 10.3389/fmed.2022.871714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundCoronavirus disease 2019 (COVID-19) has placed enormous pressure on intensive care units (ICUs) and on healthcare systems in general. A deeper understanding of the pathophysiology of the most severe forms of COVID-19 would help guide the development of more effective interventions. Herein, we characterized the inflammatory state of patients with COVID-19 of varying degrees of severity to identify admission biomarkers for predicting COVID-19 worsening.DesignAdmission blood samples were obtained from 78 patients with COVID-19. Radiographic assessment of lung edema (RALE) scoring was calculated by imaging. Platelet and leukocyte counts were measured by flow cytometry, and plasma levels of C-reactive protein were assessed by immunoturbidimetry, and interleukin (IL)-8/CXCL8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monocyte chemoattractant protein-1 (MCP-1/CCL2) levels by enzyme-linked immunosorbent assay (ELISA).ResultsThe RALE score correlated with several admission hemogram (platelets, neutrophils, and lymphocytes) and inflammatory (IL-8/CXCL8, MCP-1/CCL2, IL-10, and C-reactive protein) parameters. COVID-19 worsening, based on the need for oxygen (Δoxygen supply) during hospitalization, correlated negatively with admission lymphocyte counts but positively with neutrophil-to-lymphocyte ratio and with plasma levels of the inflammatory parameters correlating with RALE score.ConclusionOur data indicate a correlation between the RALE score and Δoxygen supply and admission inflammatory status. The identification of a panel of biomarkers that reflect COVID severity might be useful to predict disease worsening during hospitalization and to guide clinical management of COVID-19-related complications. Finally, therapies targeting IL-8/CXCL8- or IL-10 activity may offer therapeutic approaches in COVID-19 treatment.
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Affiliation(s)
- Patrice Marques
- Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
| | - Lucia Fernandez-Presa
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- Pneumology Unit, University Clinic Hospital of Valencia, Valencia, Spain
| | - Aitor Carretero
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain
| | - Maria-Carmen Gómez-Cabrera
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain
| | - José Viña
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, CIBERFES, Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain
- *Correspondence: José Viña,
| | - Jaime Signes-Costa
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- Pneumology Unit, University Clinic Hospital of Valencia, Valencia, Spain
- Jaime Signes-Costa,
| | - Maria-Jesus Sanz
- Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain
- CIBERDEM-Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders, ISCIII, Madrid, Spain
- Maria-Jesus Sanz,
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16
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Herbal Sources of Magnesium as a Promising Multifaceted Intervention for the Management of COVID-19. Nat Prod Commun 2022. [DOI: 10.1177/1934578x221116235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization (WHO), and it affected all human groups. Severe COVID-19 is characterized by cytokine storms, which can lead to multiorgan failure and death, although fever and cough are the most typical symptoms of mild COVID-19. Plant-based diets provide a 73% lower risk of moderate-to-severe COVID-19. Additionally, the association between low levels of some micronutrients and the adverse clinical consequences of COVID-19 has been demonstrated. So, nutritional therapy can become part of patient care for the survival of this life-threatening disease (COVID-19) also short-term recovery. Magnesium as an essential micronutrient due to its anti-inflammatory and beneficial effects can effectively prevent COVID-19 pandemic by playing a role in the treatment of comorbidities such as diabetes and cardiovascular disorders as major risk factors for mortality. Sufficient magnesium to stay healthy is provided by a proper daily diet, and there is usually no need to take magnesium supplements. Considering that almost half of the dietary magnesium comes from fruits, vegetables, nuts, and grains, it seems necessary to pay attention to the consumption of edible plants containing sufficient magnesium as part of the diet to prevent severe COVID-19. In this study, we have described the beneficial effects of sufficient magnesium levels to control COVID-19 and the importance of plant-based magnesium-rich diets. Additionally, we have listed some edible magnesium-rich plants.
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17
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Narazaki M, Kishimoto T. Current status and prospects of IL-6–targeting therapy. Expert Rev Clin Pharmacol 2022; 15:575-592. [DOI: 10.1080/17512433.2022.2097905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Masashi Narazaki
- Department of Advanced Clinical and Translational Immunology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
- Department of Respiratory Medicine, Clinical Immunology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
- Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Tadamitsu Kishimoto
- Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
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18
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Makaremi S, Asgarzadeh A, Kianfar H, Mohammadnia A, Asghariazar V, Safarzadeh E. The role of IL-1 family of cytokines and receptors in pathogenesis of COVID-19. Inflamm Res 2022; 71:923-947. [PMID: 35751653 PMCID: PMC9243884 DOI: 10.1007/s00011-022-01596-w] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/29/2022] [Indexed: 12/12/2022] Open
Abstract
A global pandemic has erupted as a result of the new brand coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic has been consociated with widespread mortality worldwide. The antiviral immune response is an imperative factor in confronting the recent coronavirus disease 2019 (COVID-19) infections. Meantime, cytokines recognize as crucial components in guiding the appropriate immune pathways in the restraining and eradication of the virus. Moreover, SARS-CoV-2 can induce uncontrolled inflammatory responses characterized by hyper-inflammatory cytokine production, which causes cytokine storm and acute respiratory distress syndrome (ARDS). As excessive inflammatory responses are contributed to the severe stage of the COVID-19 disease, therefore, the pro-inflammatory cytokines are regarded as the Achilles heel during COVID-19 infection. Among these cytokines, interleukin (IL-) 1 family cytokines (IL-1, IL-18, IL-33, IL-36, IL-37, and IL-38) appear to have a strong inflammatory role in severe COVID-19. Hence, understanding the underlying inflammatory mechanism of these cytokines during infection is critical for reducing the symptoms and severity of the disease. Here, the possible mechanisms and pathways involved in inflammatory immune responses are discussed.
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Affiliation(s)
- Shima Makaremi
- School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ali Asgarzadeh
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Hamed Kianfar
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.,Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Alireza Mohammadnia
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Vahid Asghariazar
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Department of Health Information Management, School of Medicine and Allied Medical Sciences, Ardabil University of Medical Sciences, Ardabil, Iran. .,Department of Microbiology, Parasitology and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
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19
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Bahoosh SR, Shokoohinia Y, Eftekhari M. Glucosinolates and their hydrolysis products as potential nutraceuticals to combat cytokine storm in SARS-COV-2. DARU : JOURNAL OF FACULTY OF PHARMACY, TEHRAN UNIVERSITY OF MEDICAL SCIENCES 2022; 30:245-252. [PMID: 35112323 PMCID: PMC8809497 DOI: 10.1007/s40199-022-00435-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 01/23/2022] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The high mortality rate in severe cases of COVID-19 is mainly due to the strong upregulation of cytokines, called a cytokine storm. Hyperinflammation and multiple organ failure comprise the main clinical features of a cytokine storm. Nrf2 is a transcription factor which regulates the expression of genes involved in immune and inflammatory processes. Furthermore, Nrf2, as a master regulator, controls the activity of NF-κB which binds to the promoter of many pro-inflammatory genes inducible of various inflammatory factors. Inhibition of Nrf2 response was recently demonstrated in biopsies from patients with COVID-19, and Nrf2 agonists inhibited SARS-CoV-2 replication across cell lines in vitro. Glucosinolates and their hydrolysis products have excellent anti-inflammatory and antioxidant effects via the Nrf2 activation pathway, reduction in the NF-κB activation, and subsequent reduced cytokines levels. CONCLUSION Accordingly, these compounds can be helpful in combating the cytokine storm associated with COVID-19.
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Affiliation(s)
- Saba Rahimi Bahoosh
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yalda Shokoohinia
- Ric Scalzo Institute for Botanical Research, Southwest College of Naturopathic Medicine, Tempe, AZ, 85282, USA
| | - Mahdieh Eftekhari
- Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, 6715847141, Kermanshah, Iran. .,Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, P.O.BOX.6714415153, Kermanshah, Iran.
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20
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Ripamonti C, Spadotto V, Pozzi P, Stevenazzi A, Vergani B, Marchini M, Sandrone G, Bonetti E, Mazzarella L, Minucci S, Steinkühler C, Fossati G. HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19. Front Immunol 2022; 13:841716. [PMID: 35592335 PMCID: PMC9111747 DOI: 10.3389/fimmu.2022.841716] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 04/01/2022] [Indexed: 01/08/2023] Open
Abstract
The COVID-19 pandemic has had a devastating impact worldwide and has been a great challenge for the scientific community. Vaccines against SARS-CoV-2 are now efficiently lessening COVID-19 mortality, although finding a cure for this infection is still a priority. An unbalanced immune response and the uncontrolled release of proinflammatory cytokines are features of COVID-19 pathophysiology and contribute to disease progression and worsening. Histone deacetylases (HDACs) have gained interest in immunology, as they regulate the innate and adaptative immune response at different levels. Inhibitors of these enzymes have already proven therapeutic potential in cancer and are currently being investigated for the treatment of autoimmune diseases. We thus tested the effects of different HDAC inhibitors, with a focus on a selective HDAC6 inhibitor, on immune and epithelial cells in in vitro models that mimic cells activation after viral infection. Our data indicate that HDAC inhibitors reduce cytokines release by airway epithelial cells, monocytes and macrophages. This anti-inflammatory effect occurs together with the reduction of monocytes activation and T cell exhaustion and with an increase of T cell differentiation towards a T central memory phenotype. Moreover, HDAC inhibitors hinder IFN-I expression and downstream effects in both airway epithelial cells and immune cells, thus potentially counteracting the negative effects promoted in critical COVID-19 patients by the late or persistent IFN-I pathway activation. All these data suggest that an epigenetic therapeutic approach based on HDAC inhibitors represents a promising pharmacological treatment for severe COVID-19 patients.
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Affiliation(s)
- Chiara Ripamonti
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Valeria Spadotto
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Pietro Pozzi
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Andrea Stevenazzi
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Barbara Vergani
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Mattia Marchini
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Giovanni Sandrone
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
| | - Emanuele Bonetti
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Luca Mazzarella
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Saverio Minucci
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
| | | | - Gianluca Fossati
- New Drug Incubator Department, Italfarmaco Group, Cinisello Balsamo, Italy
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21
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Strohl WR, Ku Z, An Z, Carroll SF, Keyt BA, Strohl LM. Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants. BioDrugs 2022; 36:231-323. [PMID: 35476216 PMCID: PMC9043892 DOI: 10.1007/s40259-022-00529-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2022] [Indexed: 12/15/2022]
Abstract
The COVID-19 pandemic is now approaching 2 years old, with more than 440 million people infected and nearly six million dead worldwide, making it the most significant pandemic since the 1918 influenza pandemic. The severity and significance of SARS-CoV-2 was recognized immediately upon discovery, leading to innumerable companies and institutes designing and generating vaccines and therapeutic antibodies literally as soon as recombinant SARS-CoV-2 spike protein sequence was available. Within months of the pandemic start, several antibodies had been generated, tested, and moved into clinical trials, including Eli Lilly's bamlanivimab and etesevimab, Regeneron's mixture of imdevimab and casirivimab, Vir's sotrovimab, Celltrion's regdanvimab, and Lilly's bebtelovimab. These antibodies all have now received at least Emergency Use Authorizations (EUAs) and some have received full approval in select countries. To date, more than three dozen antibodies or antibody combinations have been forwarded into clinical trials. These antibodies to SARS-CoV-2 all target the receptor-binding domain (RBD), with some blocking the ability of the RBD to bind human ACE2, while others bind core regions of the RBD to modulate spike stability or ability to fuse to host cell membranes. While these antibodies were being discovered and developed, new variants of SARS-CoV-2 have cropped up in real time, altering the antibody landscape on a moving basis. Over the past year, the search has widened to find antibodies capable of neutralizing the wide array of variants that have arisen, including Alpha, Beta, Gamma, Delta, and Omicron. The recent rise and dominance of the Omicron family of variants, including the rather disparate BA.1 and BA.2 variants, demonstrate the need to continue to find new approaches to neutralize the rapidly evolving SARS-CoV-2 virus. This review highlights both convalescent plasma- and polyclonal antibody-based approaches as well as the top approximately 50 antibodies to SARS-CoV-2, their epitopes, their ability to bind to SARS-CoV-2 variants, and how they are delivered. New approaches to antibody constructs, including single domain antibodies, bispecific antibodies, IgA- and IgM-based antibodies, and modified ACE2-Fc fusion proteins, are also described. Finally, antibodies being developed for palliative care of COVID-19 disease, including the ramifications of cytokine release syndrome (CRS) and acute respiratory distress syndrome (ARDS), are described.
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Affiliation(s)
| | - Zhiqiang Ku
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Sciences Center, Houston, TX USA
| | - Zhiqiang An
- Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, The University of Texas Health Sciences Center, Houston, TX USA
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22
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Veyrenche N, Pisoni A, Debiesse S, Bollore K, Bedin AS, Makinson A, Niel C, Alcocer-Cordellat C, Mondain AM, Le Moing V, Van de Perre P, Tuaillon E. SARS-CoV-2 nucleocapsid urine antigen in hospitalized patients with Covid-19. J Infect Dis 2022; 226:812-821. [PMID: 35230450 PMCID: PMC8903449 DOI: 10.1093/infdis/jiac073] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 02/28/2022] [Indexed: 12/15/2022] Open
Abstract
Background SARS-CoV-2 nucleocapsid antigen (N-Ag) can be detected in the blood of patients with Covid-19. We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of Covid-19, and explore its relationship with the severity of the disease. Methods We studied urine and blood N-Ag using highly sensitive immunoassay in 82 patients with a SARS-CoV-2 infection proven by PCR. Results In the first and second weeks of Covid-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively), and blood N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase. A higher accuracy was observed for urine N-Ag as a predictor of severe Covid-19 compared to blood N-Ag. Conclusions Our study demonstrate that N-Ag is present in the urine of patients hospitalized in the early phase of Covid-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urine N-Ag may be a useful marker for disease severity of SARS-CoV-2 infections.
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Affiliation(s)
- Nicolas Veyrenche
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles; CHU Montpellier, Montpellier, France
| | - Amandine Pisoni
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles; CHU Montpellier, Montpellier, France
| | - Ségolène Debiesse
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles, Montpellier, France
| | - Karine Bollore
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles, Montpellier, France
| | - Anne-Sophie Bedin
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles, Montpellier, France
| | - Alain Makinson
- Tropical and Infectious Diseases, University Hospital, Montpellier, France. INSERM U1175/IRD UMI 233, IRD, Montpellier, France
| | - Clémence Niel
- Montpellier University Hospital, Montpellier, France
| | | | | | - Vincent Le Moing
- Tropical and Infectious Diseases, University Hospital, Montpellier, France. INSERM U1175/IRD UMI 233, IRD, Montpellier, France
| | - Philippe Van de Perre
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles; CHU Montpellier, Montpellier, France
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic and Emerging Infections, University of Montpellier, INSERM, EFS, University of Antilles; CHU Montpellier, Montpellier, France
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23
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Zizzo G, Tamburello A, Castelnovo L, Laria A, Mumoli N, Faggioli PM, Stefani I, Mazzone A. Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling. Front Immunol 2022; 13:795315. [PMID: 35340805 PMCID: PMC8948465 DOI: 10.3389/fimmu.2022.795315] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/25/2022] [Indexed: 01/08/2023] Open
Abstract
Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.
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Affiliation(s)
- Gaetano Zizzo
- Department of Internal Medicine, Azienda Socio Sanitaria Territoriale (ASST) Ovest Milanese, Milan, Italy
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24
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KALKANLI TAŞ S, UZUNOĞLU MS, UZUNOĞLU AS, KIRKIK D, ALTUNKANAT D, KALKANLI N. Adoptive T-cell therapies to overcome T cell-dependent immune dysregulations in COVID-19. Turk J Biol 2021; 46:105-117. [PMID: 37533516 PMCID: PMC10393104 DOI: 10.3906/biy-2109-85] [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: 09/30/2021] [Revised: 04/05/2022] [Accepted: 12/20/2021] [Indexed: 08/04/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has been an important global interest that affected millions of people, and it requires a deep investigation of the disease immunology for developing further therapeutic applications. Adoptive T cell therapy promises to address T cell-dependent immune dysregulation in COVID-19 patients by the generation of specific T cell clones against virus-specific antigens. Additionally, targeting B cell-dependent protection through COVID-19 vaccines, which have been developed in the recent year, possessed sufficient prevention for spreading the virus, since the cases and deaths related to COVID-19 tend to decrease after the vaccination. However, adoptive cell therapies are now encouraging scientists to deal with pathological challenges like inadequate T cell-dependent immune response or lymphopenia, since they are the most frequent outcome of severe infection, especially in immunocompromized patients. In this review, the current knowledge of immunopathology of COVID-19 was aimed to be highlighted along with the T cell responses against SARS-CoV-2 to comprise a basis for therapeutics. Moreover, current therapeutics and treatment strategies for COVID-19 were discussed to evaluate possible agents. Furthermore, the use of adoptive T cell therapy representing an emerging therapeutic approach was purposed to be presented comprehensively against SARS-CoV-2 infection. Even though further studies are needed to fully understand T cell response against SARS-CoV-2 in order to develop therapies to provide long term and efficient protection, adoptive cell therapies now meet the demand for a large population of people who suffer immunocompromization, considering the previous usage of the technique for different infectious diseases.
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Affiliation(s)
- Sevgi KALKANLI TAŞ
- Department of Immunology, Hamidiye Medicine Faculty, University of Health Sciences, İstanbul,
Turkey
| | - Merve Saide UZUNOĞLU
- Department of Immunology, Hamidiye Institute of Health Sciences, University of Health Sciences, İstanbul,
Turkey
| | - Aylin Seher UZUNOĞLU
- Department of Immunology, Hamidiye Institute of Health Sciences, University of Health Sciences, İstanbul,
Turkey
| | - Duygu KIRKIK
- Department of Medical Biology, Hamidiye Medicine Faculty, University of Health Sciences, İstanbul,
Turkey
| | - Derya ALTUNKANAT
- Department of Medical Biology, Hamidiye Medicine Faculty, University of Health Sciences, İstanbul,
Turkey
| | - Nevin KALKANLI
- Diyarlife Hospital, Department of Dermatology, Diyarbakır,
Turkey
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25
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Singh A, Strobbe D, Campanella M. Pyroptosis targeting via mitochondria: An educated guess to innovate COVID-19 therapies. Br J Pharmacol 2021; 179:2081-2085. [PMID: 34632567 PMCID: PMC8653109 DOI: 10.1111/bph.15670] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 06/15/2021] [Accepted: 06/25/2021] [Indexed: 01/30/2023] Open
Abstract
Pyroptosis is a specialized form of inflammatory cell death which aids the defensive response against invading pathogens. Its normally tight regulation is lost during infection by the severe acute respiratory coronavirus 2 (SARS‐CoV‐2), and thus, uncontrolled pyroptosis disrupts the immune system and the integrity of organs defining the critical conditions in patients with high viral load. Molecular pathways engaged downstream of the formation and stabilization of the inflammasome, which are necessary to execute the process, have been uncovered and drugs are available for their regulation. However, the pharmacology of the upstream events, which are critical to sense and interpret the initial damage by the pathogen, is far from being elucidated. This limits our capacity to identify early markers and targets to ameliorate SARS‐CoV‐2 linked pyroptosis. Here, we focus attention on the mitochondria and pathways leading to their dysfunction, in order to elucidate the early steps of inflammasome formation and devise tools to predict and counter pathological states induced by SARS‐CoV‐2.
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Affiliation(s)
- Aarti Singh
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK
| | - Daniela Strobbe
- Department of Biology, University of Rome "Tor Vergata", Rome, Italy
| | - Michelangelo Campanella
- Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.,Department of Biology, University of Rome "Tor Vergata", Rome, Italy.,Department of Cell and Developmental Biology, Consortium for Mitochondrial Research (CfMR), University College London, London, UK
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26
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Abdalla AE, Xie J, Junaid K, Younas S, Elsaman T, Abosalif KOA, Alameen AAM, Mahjoob MO, Elamir MYM, Ejaz H. Insight into the emerging role of SARS-CoV-2 nonstructural and accessory proteins in modulation of multiple mechanisms of host innate defense. Bosn J Basic Med Sci 2021; 21:515-527. [PMID: 33714258 PMCID: PMC8381213 DOI: 10.17305/bjbms.2020.5543] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 03/04/2021] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease-19 (COVID-19) is an extremely infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has become a major global health concern. The induction of a coordinated immune response is crucial to the elimination of any pathogenic infection. However, SARS-CoV-2 can modulate the host immune system to favor viral adaptation and persistence within the host. The virus can counteract type I interferon (IFN-I) production, attenuating IFN-I signaling pathway activation and disrupting antigen presentation. Simultaneously, SARS-CoV-2 infection can enhance apoptosis and the production of inflammatory mediators, which ultimately results in increased disease severity. SARS-CoV-2 produces an array of effector molecules, including nonstructural proteins (NSPs) and open-reading frames (ORFs) accessory proteins. We describe the complex molecular interplay of SARS-CoV-2 NSPs and accessory proteins with the host's signaling mediating immune evasion in the current review. In addition, the crucial role played by immunomodulation therapy to address immune evasion is discussed. Thus, the current review can provide new directions for the development of vaccines and specific therapies.
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Affiliation(s)
- Abualgasim Elgaili Abdalla
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Omdurman, Sudan
| | - Jianping Xie
- Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing, China
| | - Kashaf Junaid
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
| | - Sonia Younas
- Department of Pathology, Tehsil Headquarter Hospital Kamoke, District Gujranwala, Kamoke, Pakistan
| | - Tilal Elsaman
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Al Jouf, Saudi Arabia
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Omdurman Islamic University, Omdurman, Sudan
| | - Khalid Omer Abdalla Abosalif
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Omdurman, Sudan
| | - Ayman Ali Mohammed Alameen
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
- Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan
| | - Mahjoob Osman Mahjoob
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Omdurman, Sudan
| | - Mohammed Yagoub Mohammed Elamir
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
- Department of Medical Microbiology, Faculty of Medical Laboratory Sciences, Omdurman Islamic University, Omdurman, Sudan
| | - Hasan Ejaz
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al Jouf, Saudi Arabia
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27
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Wittebole X, Montiel V, Mesland JB. Is there a role for immune-enhancing therapies for acutely ill patients with coronavirus disease 2019? Curr Opin Crit Care 2021; 27:480-486. [PMID: 34334626 PMCID: PMC8452248 DOI: 10.1097/mcc.0000000000000862] [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: 11/25/2022]
Abstract
PURPOSE OF REVIEW Although the so-called cytokine storm has been early described and related to a dramatic evolution in severe COVID-19 patients, it soon became clear that those patients display clinical and biological evidence of an immunosuppressive state characterized, among other, by a profound lymphopenia. The negative role of this immune suppression on the outcome raises the question on immune therapies that might improve patient's condition. RECENT FINDINGS Important positive effects of active immune therapies, such as IL-7 or thymosin-α are already described and warrant confirmation in larger prospective trials. For other therapies, such as interferons, firm conclusions for critically ill COVID-19 patients are lacking as those patients were often excluded from the published trials. Treatment with immunoglobulins or convalescent plasma is a passive strategy to provide specific immunity. Unfortunately, results from large RCTs do not support their use presently. SUMMARY In this article, we provide a review on active and passive immune boosting strategies that might help treating the most severe COVID-19 patients. We mainly focus on active strategies that include IL-7, thymosin-α, interferons, and vitamin D. Although some positive effects are described, they certainly warrant confirmation in large randomized controlled trials.
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Affiliation(s)
- Xavier Wittebole
- Critical Care Department, Cliniques universitaires St Luc, UCLouvain, Brussels, Belgium
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28
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Akwii RG, Mikelis CM. Targeting the Angiopoietin/Tie Pathway: Prospects for Treatment of Retinal and Respiratory Disorders. Drugs 2021; 81:1731-1749. [PMID: 34586603 PMCID: PMC8479497 DOI: 10.1007/s40265-021-01605-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2021] [Indexed: 12/21/2022]
Abstract
Anti-angiogenic approaches have significantly advanced the treatment of vascular-related pathologies. The ephemeral outcome and known side effects of the current vascular endothelial growth factor (VEGF)-based anti-angiogenic treatments have intensified research on other growth factors. The angiopoietin/Tie (Ang/Tie) family has an established role in vascular physiology and regulates angiogenesis, vascular permeability, and inflammatory responses. The Ang/Tie family consists of angiopoietins 1-4, their receptors, tie1 and 2 and the vascular endothelial-protein tyrosine phosphatase (VE-PTP). Modulation of Tie2 activation has provided a promising outcome in preclinical models and has led to clinical trials of Ang/Tie-targeting drug candidates for retinal disorders. Although less is known about the role of Ang/Tie in pulmonary disorders, several studies have revealed great potential of the Ang/Tie family members as drug targets for pulmonary vascular disorders as well. In this review, we summarize the functions of the Ang/Tie pathway in retinal and pulmonary vascular physiology and relevant disorders and highlight promising drug candidates targeting this pathway currently being or expected to be under clinical evaluation for retinal and pulmonary vascular disorders.
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Affiliation(s)
- Racheal Grace Akwii
- Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter St., Amarillo, TX, 79106, USA
| | - Constantinos M Mikelis
- Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1406 S. Coulter St., Amarillo, TX, 79106, USA.
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29
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Mahajan S, Choudhary S, Kumar P, Tomar S. Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens. Bioorg Med Chem 2021; 46:116356. [PMID: 34416512 PMCID: PMC8349405 DOI: 10.1016/j.bmc.2021.116356] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/30/2021] [Accepted: 07/31/2021] [Indexed: 12/21/2022]
Abstract
The ongoing COVID-19 pandemic, periodic recurrence of viral infections, and the emergence of challenging variants has created an urgent need of alternative therapeutic approaches to combat the spread of viral infections, failing to which may pose a greater risk to mankind in future. Resilience against antiviral drugs or fast evolutionary rate of viruses is stressing the scientific community to identify new therapeutic approaches for timely control of disease. Host metabolic pathways are exquisite reservoir of energy to viruses and contribute a diverse array of functions for successful replication and pathogenesis of virus. Targeting the host factors rather than viral enzymes to cease viral infection, has emerged as an alternative antiviral strategy. This approach offers advantage in terms of increased threshold to viral resistance and can provide broad-spectrum antiviral action against different viruses. The article here provides substantial review of literature illuminating the host factors and molecular mechanisms involved in innate/adaptive responses to viral infection, hijacking of signalling pathways by viruses and the intracellular metabolic pathways required for viral replication. Host-targeted drugs acting on the pathways usurped by viruses are also addressed in this study. Host-directed antiviral therapeutics might prove to be a rewarding approach in controlling the unprecedented spread of viral infection, however the probability of cellular side effects or cytotoxicity on host cell should not be ignored at the time of clinical investigations.
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Affiliation(s)
- Supreeti Mahajan
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand 247667, India
| | - Shweta Choudhary
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand 247667, India
| | - Pravindra Kumar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand 247667, India
| | - Shailly Tomar
- Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Uttarakhand 247667, India.
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30
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Choi S, Hwang S, Kwon K. Compassionate Use of GC5131 (Hyperimmunoglobulin) Therapy in Critically Ill Patients Diagnosed with COVID-19: A Case Series and Review of Literature. Viruses 2021; 13:v13091826. [PMID: 34578407 PMCID: PMC8473256 DOI: 10.3390/v13091826] [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: 07/21/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 11/16/2022] Open
Abstract
Presently, the use of convalescent plasma and hyperimmunoglobulin obtained from individuals who have recovered from coronavirus disease 2019 (COVID-19) has proved to potentially provide passive antibody-based immunity, thereby leading to several clinical trials to develop an immune-based COVID-19 treatment. However, the therapeutic efficacy of hyperimmunoglobulin in critically ill patients with COVID-19 remains unknown. On 23 October 2020, we first administered GC5131 in a compassionate-use program to critically ill patients at the Kyungpook National University, Chilgok Hospital, Korea. Since then, five more critically ill patients were treated with GC5131 in this compassionate-use program in our hospital up until 17 December 2020. We retrospectively reviewed the clinical responses of six critically ill patients diagnosed with COVID-19 who received the hyperimmunoglobulin concentrate, GC5131, which was produced by the Green Cross Corporation. After the administration of GC5131, five patients died due to an exacerbation of COVID-19 pneumonia. GC5131 was ineffective when administered to critically ill patients with COVID-19. Nevertheless, we propose that to expect a therapeutic effect from GC5131, it should be administered as early as possible to avoid the excessive inflammatory response phase in patients with severe and advanced COVID-19 infection. This step was difficult to achieve in the real world due to the time required for decision making and the process of the compassionate-use program.
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Affiliation(s)
- Sunha Choi
- Division of Pulmonary Disease, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
| | - Soyoon Hwang
- Division of Infectious Diseases, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
| | - Kitae Kwon
- Division of Infectious Diseases, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 47404, Korea;
- Correspondence: ; Tel.: +82-53-200-2616
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31
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Baral PK, Yin J, James MNG. Treatment and prevention strategies for the COVID 19 pandemic: A review of immunotherapeutic approaches for neutralizing SARS-CoV-2. Int J Biol Macromol 2021; 186:490-500. [PMID: 34237371 PMCID: PMC8256663 DOI: 10.1016/j.ijbiomac.2021.07.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 07/02/2021] [Accepted: 07/02/2021] [Indexed: 12/19/2022]
Abstract
Researchers from the world over are working to create prophylactic and therapeutic interventions to combat the COVID-19 global healthcare crisis. The current therapeutic options against the COVID-19 include repurposed drugs aimed at targets other than virus-specific proteins. Antibody-based therapeutics carry a lot of promise, and there are several of these candidates for COVID-19 treatment currently being investigated in the preclinical and clinical research stages around the world. The viral spike protein (S protein) appears to be the main target of antibody development candidates, with the majority being monoclonal antibodies. Several antibody candidates targeting the SARS-CoV-2 S protein include LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. These neutralizing antibodies will treat COVID-19 and possibly future coronavirus infections. Future studies should focus on effective immune-therapeutics and immunomodulators with the purpose of developing specific, affordable, and cost-effective prophylactic and treatment regimens to fight the COVID-19 globally.
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Affiliation(s)
- Pravas Kumar Baral
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Jiang Yin
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada
| | - Michael N G James
- Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
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32
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Umashankar A, Prakash P, Prabhu P. Sudden Sensorineural Hearing Loss Post Coronavirus Disease: A Systematic Review of Case Reports. Indian J Otolaryngol Head Neck Surg 2021; 74:3028-3035. [PMID: 34277383 PMCID: PMC8271291 DOI: 10.1007/s12070-021-02756-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/04/2021] [Indexed: 02/08/2023] Open
Abstract
The coronavirus disease of 2019 is a global pandemic disease severely affecting the upper respiratory tract that can be fatal in some instances. The virus most commonly affects the respiratory system. However, in certain cases it affects the other systems, including cardiovascular, renal, gastrointestinal, neurological, and auditory. Concerning the hearing and balance system, the microcirculation supply to the inner ear is hampered thus causing audiovestibular symptoms. Several case studies have reported sudden sensorineural hearing loss post-coronavirus disease and its detrimental impact on overall hearing. As both sudden sensorineural hearing loss and coronavirus disease deals with an emergency situation, there is a need to document case studies on how these individuals have been assessed and treated. The article has systematically reviewed these case reports involving a search strategy in databases like PubMed, PubMed Central, science direct, J-GATE, Google Scholar, and a manual Google Search.
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Affiliation(s)
- Abishek Umashankar
- All India Institute of Speech and Hearing, Mysore, Karnataka 570006 India
| | - Praveen Prakash
- All India Institute of Speech and Hearing, Mysore, Karnataka 570006 India
| | - Prashanth Prabhu
- All India Institute of Speech and Hearing, Mysore, Karnataka 570006 India
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33
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Qu HQ, Qu J, Dunn T, Snyder J, Miano TA, Connolly J, Glessner J, Anderson BJ, Reilly JP, Jones TK, Giannini HM, Agyekum RS, Weisman AR, Ittner CAG, Rodrigues LG, Kao C, Shashaty MGS, Sleiman P, Meyer NJ, Hakonarson H. Elevation of Circulating LIGHT (TNFSF14) and Interleukin-18 Levels in Sepsis-Induced Multi-Organ Injuries. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2021. [PMID: 34075388 DOI: 10.1101/2021.05.25.21257799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Objective The cytokines, LIGHT (TNFSF14) and Interleukin-18 (IL-18), are two important therapeutic targets due to their central roles in the function of activated T cells and inflammatory injury. LIGHT was recently shown to play a major role in COVID19 induced acute respiratory distress syndrome (ARDS), reducing mortality and hospital stay. This study aims to investigate the associations of LIGHT and IL-18 with non-COVID19 related ARDS, acute hypoxic respiratory failure (AHRF) or acute kidney injury (AKI), secondary to viral or bacterial sepsis. Research Design and Methods A cohort of 280 subjects diagnosed with sepsis, including 91 cases with sepsis triggered by viral infections, were investigated in this study and compared to healthy controls. Serum LIGHT, IL-18, and 59 other biomarkers (cytokines, chemokines and acute-phase reactants) were measured and associated with symptom severity. Results ARDS was observed in 36% of the patients, with 29% of the total patient cohort developing multi-organ failure (failure of two or more organs). We observed significantly increased LIGHT level (>2SD above mean of healthy subjects) in both bacterial sepsis patients (P=1.80E-05) and patients with sepsis from viral infections (P=1.78E-03). In bacterial sepsis, increased LIGHT level associated with ARDS, AKI and higher Apache III scores, findings also supported by correlations of LIGHT with other biomarkers of organ failures, suggesting LIGHT may be an inflammatory driver. IL-18 levels were highly variable across individuals, and consistently correlated with Apache III scores, mortality, and AKI, in both bacterial and viral sepsis. Conclusions For the first time, we demonstrate independent effects of LIGHT and IL-18 in septic organ failures. LIGHT levels are significantly elevated in non-COVID19 sepsis patients with ARDS and/or multi-organ failures suggesting that anti-LIGHT therapy may be effective therapy in a subset of patients with sepsis. Given the large variance of plasma IL-18 among septic subjects, targeting this pathway raises opportunities that require a precision application.
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Coperchini F, Chiovato L, Rotondi M. Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One! Front Immunol 2021; 12:668507. [PMID: 33981314 PMCID: PMC8107352 DOI: 10.3389/fimmu.2021.668507] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/06/2021] [Indexed: 12/21/2022] Open
Abstract
SARS-COV-2 virus is responsible for the ongoing devastating pandemic. Since the early phase of the pandemic, the "cytokine-storm" appeared a peculiar aspect of SARS-COV-2 infection which, at least in the severe cases, is responsible for respiratory treat damage and subsequent multi-organ failure. The efforts made in the last few months elucidated that the cytokine-storm results from a complex network involving cytokines/chemokines/infiltrating-immune-cells which orchestrate the aberrant immune response in COVID-19. Clinical and experimental studies aimed at depicting a potential "immune signature" of SARS-COV-2, identified three main "actors," namely the cytokine IL-6, the chemokine CXCL10 and the infiltrating immune cell type macrophages. Although other cytokines, chemokines and infiltrating immune cells are deeply involved and their role should not be neglected, based on currently available data, IL-6, CXCL10, and infiltrating macrophages could be considered prototype factors representing each component of the immune system. It rapidly became clear that a strong and continuous interplay among the three components of the immune response is mandatory in order to produce a severe clinical course of the disease. Indeed, while IL-6, CXCL10 and macrophages alone would not be able to fully drive the onset and maintenance of the cytokine-storm, the establishment of a IL-6/CXCL10/macrophages axis is crucial in driving the sequence of events characterizing this condition. The present review is specifically aimed at overviewing current evidences provided by both in vitro and in vivo studies addressing the issue of the interplay among IL-6, CXCL10 and macrophages in the onset and progression of cytokine storm. SARS-COV-2 infection and the "cytokine storm."
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Affiliation(s)
- Francesca Coperchini
- Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
| | - Luca Chiovato
- Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Mario Rotondi
- Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
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Tong X, Zheng Y, Li Y, Xiong Y, Chen D. Soluble ligands as drug targets for treatment of inflammatory bowel disease. Pharmacol Ther 2021; 226:107859. [PMID: 33895184 DOI: 10.1016/j.pharmthera.2021.107859] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 04/19/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by persistent inflammation in a hereditarily susceptible host. In addition to gastrointestinal symptoms, patients with IBD frequently suffer from extra-intestinal complications such as fibrosis, stenosis or cancer. Mounting evidence supports the targeting of cytokines for effective treatment of IBD. Cytokines can be included in a newly proposed classification "soluble ligands" that has become the third major target of human protein therapeutic drugs after enzymes and receptors. Soluble ligands have potential significance for research and development of anti-IBD drugs. Compared with traditional drug targets for IBD treatment, such as receptors, at least three factors contribute to the increasing importance of soluble ligands as drug targets. Firstly, cytokines are the main soluble ligands and targeting of them has demonstrated efficacy in patients with IBD. Secondly, soluble ligands are more accessible than receptors, which are embedded in the cell membrane and have complex tertiary membrane structures. Lastly, certain potential target proteins that are present in membrane-bound forms can become soluble following cleavage, providing further opportunities for intervention in the treatment of IBD. In this review, 49 drugs targeting 25 distinct ligands have been evaluated, including consideration of the characteristics of the ligands and drugs in respect of IBD treatment. In addition to approved drugs targeting soluble ligands, we have also assessed drugs that are in preclinical research and drugs inhibiting ligand-receptor binding. Some new types of targetable soluble ligands/proteins, such as epoxide hydrolase and p-selectin glycoprotein ligand-1, are also introduced. Targeting soluble ligands not only opens a new field of anti-IBD drug development, but the circulating soluble ligands also provide diagnostic insights for early prediction of treatment response. In conclusion, soluble ligands serve as the third-largest protein target class in medicine, with much potential for the drugs targeting them.
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Affiliation(s)
- Xuhui Tong
- Compartive Medicine Department of Researching and Teaching, Dalian Medical University, Dalian City 116044, Liaoning Province, China
| | - Yuanyuan Zheng
- Compartive Medicine Department of Researching and Teaching, Dalian Medical University, Dalian City 116044, Liaoning Province, China
| | - Yu Li
- Compartive Medicine Department of Researching and Teaching, Dalian Medical University, Dalian City 116044, Liaoning Province, China
| | - Yongjian Xiong
- Central Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dapeng Chen
- Compartive Medicine Department of Researching and Teaching, Dalian Medical University, Dalian City 116044, Liaoning Province, China.
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Lotfi F, Akbarzadeh-Khiavi M, Lotfi Z, Rahbarnia L, Safary A, Zarredar H, Baghbanzadeh A, Naghili B, Baradaran B. Micronutrient therapy and effective immune response: a promising approach for management of COVID-19. Infection 2021; 49:1133-1147. [PMID: 34160789 PMCID: PMC8220424 DOI: 10.1007/s15010-021-01644-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023]
Abstract
The escalating prevalence of coronavirus disease 2019 (COVID-19) worldwide, with an increased rate of morbidity and mortality, highlights an urgent need to develop more effective therapeutic interventions. Despite the authorized treatment against COVID-19 by the European Union (EU), the safety and effectiveness of this therapeutic strategy for a wide variety of patients have remained a significant challenge. In this respect, micronutrients such as vitamins and minerals, as essential factors, can be considered for improving the function of the immune system and accelerating the treatment procedure. Dietary supplements can attenuate vascular and inflammatory manifestations related to infectious diseases in large part due to their anti-inflammatory and antioxidant properties. Recently, it has been revealed that poor nutritional status may be one of the notable risk factors in severe COVID-19 infections. In the current review, we focus on the micronutrient therapy of COVID-19 patients and provide a comprehensive insight into the essential vitamins/minerals and their role in controlling the severity of the COVID-19 infection. We also discuss the recent advancements, challenges, negative and positive outcomes in relevance to this approach.
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Affiliation(s)
- Fariba Lotfi
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5163639888, Tabriz, Iran
| | - Mostafa Akbarzadeh-Khiavi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ,Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, P.O. Box 5165665811, Tabriz, Iran
| | - Ziba Lotfi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Rahbarnia
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5163639888, Tabriz, Iran
| | - Azam Safary
- Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Habib Zarredar
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Science, Tabriz, Iran
| | - Amir Baghbanzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Behrooz Naghili
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5163639888, Tabriz, Iran
| | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Aliyu M, Mozhgani SH, Gargari OK, Yusuf MA, Saboor-Yaraghi AA. The host immune responses to SARS-CoV-2 and therapeutic strategies in the treatment of COVID-19 cytokine storm. AIMS ALLERGY AND IMMUNOLOGY 2021. [DOI: 10.3934/allergy.2021018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
<abstract>
<p>The ravaging pandemic caused by SAR-CoV-2, a member of β-coronaviruses, marks the end of the year 2019. Despite being identified and classified at the earliest stage, the virus records worldwide soaring transmissibility, morbidity, and mortality. Global data have shown the infection with SARS-CoV-2 to be severe among at least 15% of the infected; the aged and those with premorbid conditions like cancer, cardiovascular, and respiratory diseases. The highest prevalence and mortality are seen in the Americas, with African countries least affected. Severe respiratory distress and multiorgan failure are the usual findings in severe cases. A hyperinflammatory, fulminant, hypercytokinemia that is often further complicated by hypercoagulopathy and multiorgan failure has been reported extensively among severely infected patients. Scientists describe hyper-activated immune response mediated by macrophages secreting copious amounts of interleukin (IL)-6 forming the epicenter of cytokine storm (CS), thereby perpetuating signaling cascade through JAK/Kinase pathway that yields a hypercytokinemia. Researchers globally are exploring JAK/kinase inhibitors, immunomodulatory (immunosuppressive) therapy, cytokines, and cytokine receptor blockers for CS management. In which interestingly some of these agents possess antiviral activity. Here, we reviewed published studies with their respective outcome. However, a lot needs to be done to address the CS of COVID-19 to avert its fatal outcome.</p>
</abstract>
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