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Osama M, Kocherry C, Ullah F, Ubaid S, Ubaid M, Ullah U, Nawaz AB, Qasem HM, Odat RM, Farhan M, Ahmed R. Odontogenic carcinosarcoma: a comprehensive review of clinical and therapeutic insights. FRONTIERS IN ORAL HEALTH 2025; 6:1544921. [PMID: 40336633 PMCID: PMC12055786 DOI: 10.3389/froh.2025.1544921] [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: 12/13/2024] [Accepted: 03/26/2025] [Indexed: 05/09/2025] Open
Abstract
Malignant odontogenic tumors are rare, accounting for only 1%-6.1% of all odontogenic tumors. Among them, odontogenic carcinosarcoma (OCS) is an exceptionally rare and aggressive malignant neoplasm originating from dental tissues. First recognized by the World Health Organization (WHO) in 1992, OCS is characterized by high-grade biphasic malignant epithelial and mesenchymal components, contributing to its aggressive clinical behavior. OCS often presents with nonspecific symptoms such as pain, swelling, and loosening of teeth, which complicate early diagnosis. Its rarity adds to the diagnostic challenges, frequently leading to delays in identification. Histopathological evaluation remains the cornerstone for accurate diagnosis, distinguishing OCS from other odontogenic tumors through features like epithelial nuclear pleomorphism, mitotic activity, and mesenchymal sarcomatous differentiation. Management typically involves surgical resection with clear margins, while adjuvant therapies such as chemotherapy and radiation are considered in select cases. Recent advancements in molecular oncology and surgical techniques, including robotic-assisted procedures and 3D-printed reconstructive aids, offer promising avenues for improving patient outcomes. A multidisciplinary approach and ongoing research are essential to enhance diagnostic accuracy, refine treatment protocols, and improve the prognosis for patients affected by this rare malignancy. The primary objective of this review is to consolidate current knowledge on OCS, focusing on its diagnostic complexities, treatment strategies, and potential emerging therapies.
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Affiliation(s)
- Muhammad Osama
- Internal Medicine, Khyber Medical College, Peshawar, Pakistan
| | - Cyril Kocherry
- School of Medicine, University of Dundee, Dundee, United Kingdom
| | - Farid Ullah
- Internal Medicine, Khyber Teaching Hospital, Peshawar, Pakistan
| | - Safiyyah Ubaid
- Department of Biochemistry, Khyber Girls Medical College, Peshawar, Pakistan
| | - Maryam Ubaid
- Public Health, Khyber Medical University, Peshawar, Pakistan
| | - Ubaid Ullah
- Department of Biochemistry, Kabir Medical College, Peshawar, Pakistan
| | | | - Hanan M. Qasem
- Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan
| | - Ramez M. Odat
- Faculty of Medicine, Jordan University of Science & Technology, Irbid, Jordan
| | - Muzammil Farhan
- Department of Cardiology, Imperial College London, London, United Kingdom
| | - Raheel Ahmed
- Department of Cardiology, National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Hashemian SM, Jafari A, Khoundabi B, Jamaati H, Rahimi P. Hemoperfusion Combined With Continuous Renal Replacement Therapy in the Management of ARDS COVID-19 Patients: A Quasi-Experimental Study. Health Sci Rep 2025; 8:e70571. [PMID: 40177411 PMCID: PMC11961550 DOI: 10.1002/hsr2.70571] [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: 11/02/2024] [Revised: 01/24/2025] [Accepted: 02/22/2025] [Indexed: 04/05/2025] Open
Abstract
Background and Aims Critically ill patients in COVID-19 to the intensive care unit (ICU) may develop multiple organ dysfunction syndrome, with some requiring extracorporeal organ support. This study aimed to assess the effects of combined CytoSorb hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the improvement of the multiorgan failure of patients with COVID-19. Methods Fifty-six patients hospitalized in the ICU with a confirmed diagnosis of COVID-19 were included in this quasi-experimental study. All the patients had acute respiratory distress syndrome (ARDS). They were treated with 1-4 sessions of HP therapy. Results Serum Interleukin-6 (IL6), C-reactive protein (CRP), d-dimer, procalcitonin (PCT), Neutrophil gelatinase-associated lipocalin (NGAL), ferritin, and bilirubin levels were decreased, while the concentration of albumin was significantly increased after HP/CRRT (p < 0.05). No significant differences were observed in O2 saturation (Sao2) and creatinine levels. Conclusion Combined HP and CRRT hold promise as a potential intervention for severe COVID-19 cases with multiple organ dysfunction, leading to improved clinical outcomes.
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Affiliation(s)
- Seyed MohammadReza Hashemian
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Ameneh Jafari
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Batoul Khoundabi
- Iran Helal Institute of Applied‐Science and TechnologyRed Crescent Society of IranTehranIran
| | - Hamidreza Jamaati
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Payam Rahimi
- Department of Anesthesiology and Reanimation, Bakırköy Dr. Sadi Konuk Training and Research HospitalUniversity of Health SciencesIstanbulTurkey
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Chen Q, Zhou Q, Yang S, Pan F, Tao H, Wen Y, Chao Y, Xie C, Ou W, Guo D, Li Y, Zhang X. Identification of adenosine analogues as nsp14 N7‑methyltransferase inhibitors for treating coronaviruses infection. Bioorg Chem 2024; 153:107894. [PMID: 39490138 DOI: 10.1016/j.bioorg.2024.107894] [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: 09/06/2024] [Revised: 10/10/2024] [Accepted: 10/14/2024] [Indexed: 11/05/2024]
Abstract
Coronaviruses are RNA viruses that have coevolved with humans and animals over time, exhibiting high mutation rates and mortality rates upon epidemic outbreaks. The nonstructural protein (nsp14) is crucial for various coronaviruses processes, including genome replication, protein translation, virus particle assembly, and evasion of host immunity via RNA methylation modification. In this study, a series of adenosine analogs were designed, synthesized, and evaluated for their inhibitory activities. Among them, MTI013 exhibited the strongest nsp14 MTase inhibition and antiviral activity, with an IC50 of 10.33 μM in HCoV-229E-infected Huh7 cells, along with low cytotoxicity. When combined with the RdRp inhibitor ATV014, MTI013 showed a synergistic antiviral effect, indicating its potential both as a standalone therapy and in combination treatments. Furthermore, MTI013 displayed high selectivity against the SARS-CoV-2 nsp10-nsp16 complex and five human methyltransferases. These results offer valuable structural insights for future exploration of nsp14 as a drug target for SARS-CoV-2 and other coronaviruses.
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Affiliation(s)
- Qishu Chen
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China
| | - Qifan Zhou
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China.
| | - Sidi Yang
- Guangzhou National Laboratory, Guangzhou, Guangdong Province 510005, China
| | - Fan Pan
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China
| | - Hongqi Tao
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China
| | - Yuanmei Wen
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China
| | - Yang Chao
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China
| | - Cailing Xie
- Guangzhou National Laboratory, Guangzhou, Guangdong Province 510005, China
| | - Weixin Ou
- Guangzhou National Laboratory, Guangzhou, Guangdong Province 510005, China
| | - Deyin Guo
- Guangzhou National Laboratory, Guangzhou, Guangdong Province 510005, China.
| | - Yingjun Li
- State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510180, China.
| | - Xumu Zhang
- Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Academy for Advanced Interdisciplinary Studies and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, Guangdong 518000, China.
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Mubarak A, Alqoufail M, Almutairi S, Alrfaei B, Almotairi A, Aziz I, Almanaa TN, Abdel-Maksoud MA, Farrag MA, Aldreiwish AD, Awadalla ME, Alosaimi B, Alturaiki W. MERS-CoV Infection and Its Impact on the Expression of TSLP Cytokine and IgG Antibodies: An In Vivo and In Vitro Study. Infect Drug Resist 2024; 17:4589-4598. [PMID: 39469096 PMCID: PMC11513571 DOI: 10.2147/idr.s483133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 10/08/2024] [Indexed: 10/30/2024] Open
Abstract
Purpose Thymic stromal lymphopoietin (TSLP) is a proinflammatory cytokine produced by epithelial cells that is involved in the activation of allergic disorders. To date, no study has examined TSLP induction during Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Herein, we aimed to study the effects of the recombinant spike protein of MERS-CoV on TSLP production. Additionally, the effects of recombinant human TSLP (rhTSLP) on B cell survival and antibody production were investigated. Patients and Methods B cells were separated using the Human B Cell Enrichment Kit, and B cell survival was measured using the WST-1 Assay Kit. Enzyme-linked immunosorbent assay (ELISA) was used to measure TSLP levels in the sera of both MERS-CoV-infected (n=4; median age, 53 years) and healthy individuals (n=5; median age, 35 years). Results We showed that the group of infected patients had significantly higher levels of TSLP than healthy controls (37.6 pg/mL vs 19.8 pg/mL, *p<0.05). The levels of TSLP in A549 cells were remarkably increased after 48 h of stimulation with recombinant full-length spike protein (rSP) (32.2 pg/mL, p=0.01). B cell survival was greatly enhanced by rhTSLP alone or in combination with rSP (0.02 vs 0.046, and 0.045; **p<0.01, respectively). Our data also showed a significant synergistic effect of rhTSLP and rSP on the augmented response of IgG antibodies against the spike protein of MERS-CoV compared with unstimulated cells (0.156 vs 0.22; *p<0.05). Conclusion TSLP production is induced in vivo after MERS-CoV infection and in vitro after treatment with the rSP of MERS-CoV, which has a significant effect on the survival of B cells. Our data suggest that TSLP can be used as a strong mucosal adjuvant for vaccine development against MERS-CoV infection. However, further investigation is required to study the functional role of TSLP in MERS-CoV infection.
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Affiliation(s)
- Ayman Mubarak
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Mahfoudh Alqoufail
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Saeedah Almutairi
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Bahauddeen Alrfaei
- Stem Cells Unit, Department of Cellular Therapy, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Science, MNGHA, Riyadh, Saudi Arabia
| | | | - Ibrahim Aziz
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Taghreed N Almanaa
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Mostafa A Abdel-Maksoud
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Mohamed A Farrag
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia
| | - Allolo D Aldreiwish
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia
| | - Maaweya E Awadalla
- Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, Saudi Arabia
| | - Bandar Alosaimi
- Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, Saudi Arabia
| | - Wael Alturaiki
- Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, 11952, Saudi Arabia
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Huang DY, Luo YX, Zheng WD, Wu SY, Huang PQ, Jin JW, Wu PP, Gan LS. Anti-coronavirus and anti-pulmonary inflammation effects of iridoids, the common component from Chinese herbal medicines for the treatment of COVID-19. J Nat Med 2024; 78:1003-1012. [PMID: 38775895 DOI: 10.1007/s11418-024-01820-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 04/22/2024] [Indexed: 08/31/2024]
Abstract
The practice of Chinese herbal medicines for the treatment of COVID-19 in China played an essential role for the control of mortality rate and reduction of recovery time. The iridoids is one of the main constituents of many heat-clearing and detoxifying Chinese medicines that were largely planted and frequently used in clinical practice. Twenty-three representative high content iridoids from several staple Chinese medicines were obtained and tested by a SARS-CoV-2 pseudo-virus entry-inhibition assay on HEK-293 T/ACE2 cells, a live HCoV-OC43 virus infection assay on HRT-18 cells, and a SARS-CoV-2 3CL protease inhibitory FRET assay followed by molecular docking simulation. The anti-pulmonary inflammation activities were further evaluated on a TNF-α induced inflammation model in A549 cells and preliminary SARs were concluded. The results showed that specnuezhenide (7), cornuside (12), neonuezhenide (15), and picroside III (21) exhibited promising antiviral activities, and neonuezhenide (15) could inhibit 3CL protease with an IC50 of 14.3 μM. Docking computation showed that compound 15 could bind to 3CL protease through a variety of hydrogen bonding and hydrophobic interactions. In the anti-pulmonary inflammation test, cornuside (12), aucubin (16), monotropein (17), and shanzhiside methyl ester (18) could strongly decrease the content of IL-1β and IL-8 at 10 μM. Compound 17 could also upregulate the expression of the anti-inflammatory cytokine IL-10 significantly. The iridoids exhibited both anti-coronavirus and anti-pulmonary inflammation activities for their significance of existence in Chinese herbal medicines, which also provided a theoretical basis for their potential utilization in the pharmaceutical and food industries.
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Affiliation(s)
- Dan-Yu Huang
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 260 Baichuan St, Hangzhou, 311402, People's Republic of China
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China
| | - Yong-Xin Luo
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China
| | - Wen-De Zheng
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China
| | - Shu-Yu Wu
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 260 Baichuan St, Hangzhou, 311402, People's Republic of China
| | - Pei-Qi Huang
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China
| | - Jing-Wei Jin
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China
| | - Pan-Pan Wu
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China.
| | - Li-She Gan
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, 260 Baichuan St, Hangzhou, 311402, People's Republic of China.
- School of Pharmacy and Food Engineering, International Healthcare Innovation Institute, Wuyi University, 99 Yingbin Ave, 529020, Jiangmen, People's Republic of China.
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Rasul HO, Thomas NV, Ghafour DD, Aziz BK, Salgado M G, Mendoza-Huizar LH, Candia LG. Searching possible SARS-CoV-2 main protease inhibitors in constituents from herbal medicines using in silico studies. J Biomol Struct Dyn 2024; 42:4234-4248. [PMID: 37349945 DOI: 10.1080/07391102.2023.2220040] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 05/23/2023] [Indexed: 06/24/2023]
Abstract
The largest threat to civilization since the Second World War is the spread of the new coronavirus disease (COVID-19). Therefore, there is an urgent need for innovative therapeutic medicines to treat COVID-19. Reusing bio-actives is a workable and efficient strategy in the battle against new epidemics because the process of developing new drugs is time-consuming. This research aimed to identify which herbal remedies had the highest affinity for the receptor and assess a variety of them for potential targets to suppress the SARS-CoV-2 Mpro. The use of AutoDock Vina for structure-based virtual screening was done first due to the importance of protein interactions in the development of drugs. Molecular docking was used in the comparative study to assess 89 different chemicals from medicinal herbs. To anticipate their effectiveness against the primary protease of SARS-CoV-2, more analysis was done on the ADMET profile, drug-likeness, and Lipinski's rule of five. The next step involved three replicas of 100 ns-long molecular dynamics simulations on the potential candidates, which were preceded by calculations of the binding free energy of MM-GBSA. The outcomes showed that Achyrodimer A, Cinchonain Ib, Symphonone F, and Lupeol acetate all performed well and had the highest 6LU7 binding affinities. Using RMSD, RMSF, and protein-ligand interactions, the stability of the protein-ligand complex was assessed. The studies indicate that bioactive substances obtained from herbal medicines may function as a COVID-19 therapeutic agent, necessitating additional wet lab research to confirm their therapeutic potential, efficacy, and pharmacological capacity against the condition.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Hezha O Rasul
- Department of Pharmaceutical Chemistry, College of Science, Charmo University, Chamchamal, Sulaimani, Iraq
| | - Noel Vinay Thomas
- Department of BioMedical Science, College of Science, Komar University of Science and Technology, Sulaimani, Iraq
| | - Dlzar D Ghafour
- Department of Medical Laboratory Science, College of Science, Komar University of Science and Technology, Sulaimani, Iraq
- Department of Chemistry, College of Science, University of Sulaimani, Sulaimani, Iraq
| | - Bakhtyar K Aziz
- Department of Nanoscience and Applied Chemistry, College of Science, Charmo University, Chamchamal, Sulaimani, Iraq
| | | | - L H Mendoza-Huizar
- Academic Area of Chemistry, Mineral de la Reforma, Autonomous University of Hidalgo State, Hidalgo, México
| | - Lorena Gerli Candia
- Departamento de Química Ambiental, Facultad de Ciencias, Universidad Católica de la Santísima Concepción, Concepción, Chile
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Khafaei M, Asghari R, Zafari F, Sadeghi M. Impact of IL-6 rs1800795 and IL-17A rs2275913 gene polymorphisms on the COVID-19 prognosis and susceptibility in a sample of Iranian patients. Cytokine 2024; 174:156445. [PMID: 38056249 DOI: 10.1016/j.cyto.2023.156445] [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: 08/08/2023] [Revised: 09/23/2023] [Accepted: 11/13/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND From asymptomatic to acute and life-threatening pulmonary infection, the clinical manifestations of COVID-19 are highly variable. Interleukin (IL)-6 and IL-17A are key drivers of hyper inflammation status in COVID-19, and their elevated levels are hallmarks of the infection progression. To explore whether prognosis and susceptibility to COVID-19 are linked to IL-6 rs1800795 and IL-17A rs2275913, these single-nucleotide polymorphisms (SNPs) were assessed in a sample of Iranian COVID-19 patients. METHODS This study enrolled two hundred and eighty COVID-19 patients (140 non-severe and 140 severe). Genotyping for IL-6 rs1800795 and IL-17A rs2275913 was performed using tetra primer-amplification refractory mutation system-polymerase chain reaction (tetra-ARMS-PCR). IL-6 and IL-17A circulating levels were measured using enzyme-linked immunosorbent assay (ELISA). Also, mortality predictors of COVID-19 were investigated. RESULTS The rs1800795 GG genotype (78/140 (55.7 %)) and G allele (205/280 (73.2 %)) were significantly associated with a positive risk of COVID-19 severe infection (OR = 2.19, 95 %CI: 1.35-3.54, P =.006 and OR = 1.79, 95 %CI: 1.25-2.56, P <.001, respectively). Also, rs1800795 GG genotype was significantly linked to disease mortality (OR = 1.95, 95 %CI: 1.06-3.61, P =.04). The rs2275913 GA genotype was protective against severe COVID-19 (OR = 0.5, 95 %CI: 0.31--0.80, P =.012). However, the present study did not reveal any significant link between rs2275913 genotypes with disease mortality. INR ≥ 1.2 (OR = 2.19, 95 %CI: 1.61-3.78, P =.007), D-dimer ≥ 565.5 ng/mL (OR = 3.12, 95 %CI: 1.27-5.68, P =.019), respiratory rate ≥ 29 (OR = 1.19, 95 %CI: 1.12-1.28, P =.001), IL-6 serum concentration ≥ 28.5 pg/mL (OR = 1.97, 95 %CI: 1.942-2.06, P =.013), and IL-6 rs1800795 GG genotype (OR = 1.95, 95 %CI: 1.06-3.61, P =.04) were predictive of COVID-19 mortality. CONCLUSION The rs1800795 GG genotype and G allele were associated with disease severity, and INR, D-dimer, respiratory rate, IL-6 serum concentration, and IL-6 rs1800795 GG genotype were predictive of COVID-19 mortality.
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Affiliation(s)
- Mostafa Khafaei
- Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Reza Asghari
- Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Fariba Zafari
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.
| | - Morteza Sadeghi
- Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Humbert MV, McCormick CJ, Spalluto CM. SARS-CoV-2 Infection of Human Primary Nasal Multiciliated Epithelial Cells Grown on Air-Liquid Interface Cultures. Methods Mol Biol 2024; 2725:27-53. [PMID: 37856016 DOI: 10.1007/978-1-0716-3507-0_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2023]
Abstract
Respiratory epithelial cells fail to exhibit natural phenotypic and morphological characteristics when grown in standard cell culture conditions. To better understanding respiratory pathogen host-cell interactions in the airways, one approach is to instead grow and differentiate these cells at an air-liquid interface (ALI). This chapter provides the working protocols used in our lab for producing ALI cultures, infecting them with SARS-CoV-2 and monitoring viral replication.
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Affiliation(s)
- Maria Victoria Humbert
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge, Cambridge, UK
| | - Christopher J McCormick
- Faculty of Medicine, School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK
- Southampton NIHR Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Cosma Mirella Spalluto
- Faculty of Medicine, School of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
- Southampton NIHR Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
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Pamulapati BK, Nanjundappa RK, Chandrabhatla BS, Roohi SU, Palepu S. Correlation of Computed Tomography (CT) Severity Score With Laboratory and Clinical Parameters and Outcomes in Coronavirus Disease 2019 (COVID-19). Cureus 2024; 16:e52324. [PMID: 38361692 PMCID: PMC10867700 DOI: 10.7759/cureus.52324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2024] [Indexed: 02/17/2024] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a potentially lethal respiratory illness caused by a newly identified coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the novelty of the virus, high caseloads, and increasing turnaround time for reverse transcriptase-polymerase chain reaction (RT-PCR) results, accurate information about the clinical course and prognosis of individual patients was largely unknown. This has forced physicians all over the world to brainstorm attempts to come up with reliable indicators like chest high-resolution computed tomography (HRCT) for any changes suggestive of COVID-19; surrogate laboratory parameters such as C-reactive protein (CRP), ferritin, D-dimer, lactate dehydrogenase (LDH), or interleukin-6 (IL-6) for assessing the severity of the disease; and other organ-specific tests to identify the multiorgan involvement in severe-to-critical COVID-19. Chest computed tomography (CT) scans play a significant role in the management of COVID-19 disease and serve as an indicator of disease severity and its possible outcome, which might help in the early identification of patients who might need critical care and earlier prognostication. METHODS A retrospective observational study was conducted at a single center in a level 3 critical care unit (CCU) of a 750-bed teaching hospital in Hyderabad, Telangana, India, over a period of six months. All RT-PCR-positive COVID-19 patients admitted to the CCU with CT chest performed within 24 hours of admission were screened for eligibility for this study. CT severity scoring was based on chest HRCT or CT. RESULTS Of the 110 patients, a majority (36.36%) were aged between 61 and 70 years. The mean age of our study population was 59.65±11.88 years. Of the 110 patients, the majority were admitted to the hospital for 22-28 days (24.55%), followed by 8-14 days (22.72%), and 21.82% were admitted for one day. Of the 110 patients, a majority were admitted to the CCU for seven days (41.82%), followed by 15-21 days (24.55%); and 19.09% were admitted for 8-14 days. Most of the patients were discharged (65.45%), and we had a 34.55% mortality rate in our study. We found a significant association between chest CT severity score (CTSS) and the age of the patient, duration of hospital stay, and duration of CCU stay using multivariate regression analysis. CONCLUSION CTSS could be greatly helpful for the screening and early identification of the disease, especially in those patients awaiting an RT-PCR report or with negative RT-PCR, which would lead to appropriate isolation and treatment measures. Early detection could also help assess the progression of the disease, alter the course of management at the earliest point possible, and improve the prognostication of COVID-19 patients.
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Affiliation(s)
| | | | | | - Sumayya U Roohi
- Critical Care Medicine, Citizens Specialty Hospital, Hyderabad, IND
| | - Sushrut Palepu
- Critical Care Medicine, Citizens Specialty Hospital, Hyderabad, IND
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Ludhiadch A, Paul SR, Khan R, Munshi A. COVID-19 induced ischemic stroke and mechanisms of viral entry in brain and clot formation: a systematic review and current update. Int J Neurosci 2023; 133:1153-1166. [PMID: 35412938 DOI: 10.1080/00207454.2022.2056460] [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: 11/29/2021] [Accepted: 03/16/2022] [Indexed: 10/18/2022]
Abstract
Background: Coronavirus disease 2019, caused by SARS-CoV-2 (SCV-2) was stated as a pandemic on March 11 2020 by World Health Organization (WHO), and since then, it has become a major health issue worldwide. It mainly attacks the respiratory system with various accompanying complications, including cardiac injury, renal failure, encephalitis and Stroke.Materials and Methods: The current systematic review has been compiled to summarize the available literature on SCV-2 induced ischemic Stroke and its subtypes. Further, the mechanisms by which the virus crosses the blood-brain barrier (BBB) to enter the brain have also been explored. The role of CRP and D-dimer as potent prognostic markers was also explored. The literature search was carried out comprehensively on Google scholar, PubMed, SCOP US, Embase and Cochrane databases by following guidelines.Results: All the studies were reviewed thoroughly by authors and disagreements were resolved by consensus and help of the senior authors. The most common subtype of the IS was found to be large artery atherosclerosis in SCV-2 induced IS. Hypertension emerged as the most significant risk factor. The mechanism resulting in elevated levels of CRP and D-dimer have also been discussed. However, there is a scarcity of definitive evidence on how SCV-2 enters the human brain. The available literature based on various studies demonstrated that SCV-2 enters through the nasopharyngeal tract via olfactory cells to olfactory neurons, astrocytes and via choroid plexus through endothelial cells. Further, disruption of gut-brain axis has been also discussed.Conclusion: Data available in the literature is not adequate to come to a conclusion. Therefore, there is a need to carry out further studies to delineate the possible association between SCV-2 induced IS.
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Affiliation(s)
- Abhilash Ludhiadch
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Swaraj Ranjan Paul
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Rahul Khan
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
| | - Anjana Munshi
- Department of Human Genetics and Molecular Medicine Central, University of Punjab Bathinda, Bathinda, Punjab, India
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11
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Fritch EJ, Mordant AL, Gilbert TSK, Wells CI, Yang X, Barker NK, Madden EA, Dinnon KH, Hou YJ, Tse LV, Castillo IN, Sims AC, Moorman NJ, Lakshmanane P, Willson TM, Herring LE, Graves LM, Baric RS. Investigation of the Host Kinome Response to Coronavirus Infection Reveals PI3K/mTOR Inhibitors as Betacoronavirus Antivirals. J Proteome Res 2023; 22:3159-3177. [PMID: 37634194 DOI: 10.1021/acs.jproteome.3c00182] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
Abstract
Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an attractive class of compounds to repurpose for host-targeted therapies against emerging coronavirus infections. To further understand the host kinome response to betacoronavirus infection, we employed multiplex inhibitory bead mass spectrometry (MIB-MS) following MERS-CoV and SARS-CoV-2 infection of human lung epithelial cell lines. Our MIB-MS analyses revealed activation of mTOR and MAPK signaling following MERS-CoV and SARS-CoV-2 infection, respectively. SARS-CoV-2 host kinome responses were further characterized using paired phosphoproteomics, which identified activation of MAPK, PI3K, and mTOR signaling. Through chemogenomic screening, we found that clinically relevant PI3K/mTOR inhibitors were able to inhibit coronavirus replication at nanomolar concentrations similar to direct-acting antivirals. This study lays the groundwork for identifying broad-acting, host-targeted therapies to reduce betacoronavirus replication that can be rapidly repurposed during future outbreaks and epidemics. The proteomics, phosphoproteomics, and MIB-MS datasets generated in this study are available in the Proteomics Identification Database (PRIDE) repository under project identifiers PXD040897 and PXD040901.
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Affiliation(s)
- Ethan J Fritch
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
| | - Angie L Mordant
- UNC Michael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Thomas S K Gilbert
- Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, United States
| | - Carrow I Wells
- Structural Genomics Consortium, Department of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7264, United States
| | - Xuan Yang
- Structural Genomics Consortium, Department of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7264, United States
| | - Natalie K Barker
- UNC Michael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Emily A Madden
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
| | - Kenneth H Dinnon
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
| | - Yixuan J Hou
- Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, United States
| | - Longping V Tse
- Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, United States
| | - Izabella N Castillo
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
| | - Amy C Sims
- Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, United States
| | - Nathaniel J Moorman
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
| | - Premkumar Lakshmanane
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
| | - Timothy M Willson
- Structural Genomics Consortium, Department of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7264, United States
| | - Laura E Herring
- UNC Michael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, United States
| | - Lee M Graves
- UNC Michael Hooker Proteomics Core, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
- Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, United States
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
| | - Ralph S Baric
- Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7290, United States
- Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7400, United States
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, United States
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12
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Sessions Z, Bobrowski T, Martin HJ, Beasley JMT, Kothari A, Phares T, Li M, Alves VM, Scotti MT, Moorman NJ, Baric R, Tropsha A, Muratov EN. Praemonitus praemunitus: can we forecast and prepare for future viral disease outbreaks? FEMS Microbiol Rev 2023; 47:fuad048. [PMID: 37596064 PMCID: PMC10532129 DOI: 10.1093/femsre/fuad048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 07/04/2023] [Accepted: 08/17/2023] [Indexed: 08/20/2023] Open
Abstract
Understanding the origins of past and present viral epidemics is critical in preparing for future outbreaks. Many viruses, including SARS-CoV-2, have led to significant consequences not only due to their virulence, but also because we were unprepared for their emergence. We need to learn from large amounts of data accumulated from well-studied, past pandemics and employ modern informatics and therapeutic development technologies to forecast future pandemics and help minimize their potential impacts. While acknowledging the complexity and difficulties associated with establishing reliable outbreak predictions, herein we provide a perspective on the regions of the world that are most likely to be impacted by future outbreaks. We specifically focus on viruses with epidemic potential, namely SARS-CoV-2, MERS-CoV, DENV, ZIKV, MAYV, LASV, noroviruses, influenza, Nipah virus, hantaviruses, Oropouche virus, MARV, and Ebola virus, which all require attention from both the public and scientific community to avoid societal catastrophes like COVID-19. Based on our literature review, data analysis, and outbreak simulations, we posit that these future viral epidemics are unavoidable, but that their societal impacts can be minimized by strategic investment into basic virology research, epidemiological studies of neglected viral diseases, and antiviral drug discovery.
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Affiliation(s)
- Zoe Sessions
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Tesia Bobrowski
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Holli-Joi Martin
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Jon-Michael T Beasley
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Aneri Kothari
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Trevor Phares
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
- School of Chemistry, University of Louisville, 2320 S Brook St, Louisville, KY 40208, United States
| | - Michael Li
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Vinicius M Alves
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Marcus T Scotti
- Department of Pharmaceutical Sciences, Federal University of Paraiba, Campus I Lot. Cidade Universitaria, PB, 58051-900, Brazil
| | - Nathaniel J Moorman
- Department of Microbiology and Immunology, University of North Carolina, 116 Manning Drive, Chapel Hill, NC 27599, United States
| | - Ralph Baric
- Department of Epidemiology, University of North Carolina, 401 Pittsboro St, Chapel Hill, NC 27599, United States
| | - Alexander Tropsha
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
| | - Eugene N Muratov
- Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, 301 Pharmacy Ln, Chapel Hill, NC 27599, United States
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13
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Kumari K, Nandi A, Sinha A, Ghosh A, Sengupta S, Saha U, Singh PK, Panda PK, Raina V, Verma SK. The paradigm of prophylactic viral outbreaks measures by microbial biosurfactants. J Infect Public Health 2023; 16:575-587. [PMID: 36840992 PMCID: PMC9940476 DOI: 10.1016/j.jiph.2023.02.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/19/2023] [Accepted: 02/16/2023] [Indexed: 02/22/2023] Open
Abstract
The recent emergence and outbreak of the COVID-19 pandemic confirmed the incompetence of countries across the world to deal with a global public health emergency. Although the recent advent of vaccines is an important prophylactic measure, effective clinical therapy for SARS-Cov-2 is yet to be discovered. With the increasing mortality rate, research has been focused on understanding the pathogenic mechanism and clinical parameters to comprehend COVID-19 infection and propose new avenues for naturally occurring molecules with novel therapeutic properties to alleviate the current situation. In accordance with recent clinical studies and SARS-CoV-2 infection markers, cytokine storm and oxidative stress are entwined pathogenic processes in COVID-19 progression. Lately, Biosurfactants (BSs) have been studied as one of the most advanced biomolecules of microbial origin with anti-inflammatory, antioxidant, antiviral properties, antiadhesive, and antimicrobial properties. Therefore, this review inspects available literature and proposes biosurfactants with these properties to be encouraged for their extensive study in dealing with the current pandemic as new pharmaceutics in the prevention and control of viral spread, treating the symptoms developed after the incubation period through different therapeutic approaches and playing a potential drug delivery model.
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Affiliation(s)
- Khushbu Kumari
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Aditya Nandi
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Adrija Sinha
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Aishee Ghosh
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Srabasti Sengupta
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Utsa Saha
- School of Biotechnology, KIIT Deemed to be University, 751024, India
| | - Pawan K Singh
- BVG Life Sciences Limited, Sagar Complex, Near Nashikphata, Old Pune-Mumbai Road, Chinchwad, Pune 411034, India
| | - Pritam Kumar Panda
- Department of Physics and Astronomy, Uppsala University, Box 516, SE-75120 Uppsala, Sweden.
| | - Vishakha Raina
- School of Biotechnology, KIIT Deemed to be University, 751024, India.
| | - Suresh K Verma
- School of Biotechnology, KIIT Deemed to be University, 751024, India.
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14
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Moore KA, Leighton T, Ostrowsky JT, Anderson CJ, Danila RN, Ulrich AK, Lackritz EM, Mehr AJ, Baric RS, Baylor NW, Gellin BG, Gordon JL, Krammer F, Perlman S, Rees HV, Saville M, Weller CL, Osterholm MT. A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy. Vaccine 2023; 41:2101-2112. [PMID: 36870874 PMCID: PMC9941884 DOI: 10.1016/j.vaccine.2023.02.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 02/10/2023] [Indexed: 02/23/2023]
Abstract
Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of future outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap (CVR) is aimed at promoting the development of such vaccines. The CVR, funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation, was generated through a collaborative and iterative process, which was led by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota and involved 50 international subject matter experts and recognized leaders in the field. This report summarizes the major issues and areas of research outlined in the CVR and identifies high-priority milestones. The CVR covers a 6-year timeframe and is organized into five topic areas: virology, immunology, vaccinology, animal and human infection models, and policy and finance. Included in each topic area are key barriers, gaps, strategic goals, milestones, and additional R&D priorities. The roadmap includes 20 goals and 86 R&D milestones, 26 of which are ranked as high priority. By identifying key issues, and milestones for addressing them, the CVR provides a framework to guide funding and research campaigns that promote the development of broadly protective coronavirus vaccines.
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Affiliation(s)
- Kristine A Moore
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA; Center for Infectious Disease Research and Policy, C315 Mayo Memorial Building, MMC 263, 420 Delaware Street, SE, Minneapolis, Minnesota 55455, USA.
| | - Tabitha Leighton
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Julia T Ostrowsky
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Cory J Anderson
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | | | - Angela K Ulrich
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Eve M Lackritz
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Angela J Mehr
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
| | - Ralph S Baric
- University of North Carolina, Chapel Hill, North Carolina, USA
| | | | | | - Jennifer L Gordon
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Florian Krammer
- Department of Microbiology, Department of Pathology, Molecular and Cell-Based Medicine, and Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York City, New York, USA
| | | | - Helen V Rees
- Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Melanie Saville
- Coalition for Epidemic Preparedness Innovations, London, United Kingdom
| | | | - Michael T Osterholm
- Center for Infectious Disease Research and Policy, University of Minnesota, Minneapolis, Minnesota, USA
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15
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Verma S, Verma S, Khan FH, Siddiqi Z, Raza ST, Abbas M, Mahdi F. Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity. Int J Immunogenet 2023; 50:5-11. [PMID: 36323530 PMCID: PMC9878250 DOI: 10.1111/iji.12605] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/27/2022] [Accepted: 10/16/2022] [Indexed: 11/06/2022]
Abstract
Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.
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Affiliation(s)
- Shrikant Verma
- Department of Personalized and Molecular MedicineEra UniversityLucknowUttar PradeshIndia
| | - Sushma Verma
- Department of Personalized and Molecular MedicineEra UniversityLucknowUttar PradeshIndia
| | | | - Zeba Siddiqi
- Department of MedicineEras Lucknow Medical College and HospitalEra UniversityLucknowUttar PradeshIndia
| | - Syed Tasleem Raza
- Department of BiochemistryEras Lucknow Medical College and HospitalEra UniversityLucknowUttar PradeshIndia
| | - Mohammad Abbas
- Department of Personalized and Molecular MedicineEra UniversityLucknowUttar PradeshIndia,Department of MicrobiologyEra UniversityLucknowUttar PradeshIndia
| | - Farzana Mahdi
- Department of Personalized and Molecular MedicineEra UniversityLucknowUttar PradeshIndia
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16
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Lefèvre C, Plocque A, Tran M, Creux M, Philippart F. [Should we interfere with the interleukin-6 receptor during COVID-19: What do we know?]. Rev Mal Respir 2023; 40:24-37. [PMID: 36577608 PMCID: PMC9791331 DOI: 10.1016/j.rmr.2022.11.085] [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: 09/20/2022] [Accepted: 11/30/2022] [Indexed: 12/13/2022]
Abstract
COVID-19 is a viral infection with predominant respiratory tropism. In its most severe forms, the initial viral aggression leads to acute respiratory failure due to damage secondary to an exacerbated inflammatory response provoked by the activation of innate, followed by adaptive immunity. The inflammatory response may entail respiratory distress syndrome, if not multivisceral failure and death. IL-6 receptor inhibitors (Tocilizumab and Sarilumab) have been proposed as treatments. Numerous studies have provided new information, which remains heterogeneous and difficult to interpret. This review is aimed at clarifying the potential role of IL-6 receptor inhibitors in severe forms of COVID-19.
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Affiliation(s)
- C Lefèvre
- Medical and Surgical Intensive Care Unit, groupe hospitalier Paris Saint-Joseph, Paris, France
| | - A Plocque
- Medical and Surgical Intensive Care Unit, groupe hospitalier Paris Saint-Joseph, Paris, France
| | - M Tran
- Medical and Surgical Intensive Care Unit, groupe hospitalier Paris Saint-Joseph, Paris, France
| | - M Creux
- Medical and Surgical Intensive Care Unit, groupe hospitalier Paris Saint-Joseph, Paris, France
| | - F Philippart
- Medical and Surgical Intensive Care Unit, groupe hospitalier Paris Saint-Joseph, Paris, France; Endotoxins, Structures and Host Response, Department of Microbiology, Institute for Integrative Biology of the Cell, UMR 9891 CNRS-CEA-Paris Saclay University, 98190 Gif-sur-Yvette, France.
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17
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Plocque A, Mitri C, Lefèvre C, Tabary O, Touqui L, Philippart F. Should We Interfere with the Interleukin-6 Receptor During COVID-19: What Do We Know So Far? Drugs 2023; 83:1-36. [PMID: 36508116 PMCID: PMC9743129 DOI: 10.1007/s40265-022-01803-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2022] [Indexed: 12/14/2022]
Abstract
Severe manifestations of COVID-19 consist of acute respiratory distress syndrome due to an initially local reaction leading to a systemic inflammatory response that results in hypoxia. Many therapeutic approaches have been attempted to reduce the clinical consequences of an excessive immune response to viral infection. To date, systemic corticosteroid therapy is still the most effective intervention. More recently, new hope has emerged with the use of interleukin (IL)-6 receptor inhibitors (tocilizumab and sarilumab). However, the great heterogeneity of the methodology and results of published studies obfuscate the true value of this treatment, leading to a confusing synthesis in recent meta-analyses, and the persistence of doubts in terms of patient groups and the appropriate time to treat. Moreover, their effects on the anti-infectious or pro-healing response are still poorly studied. This review aims to clarify the potential role of IL-6 receptor inhibitors in the treatment of severe forms of COVID-19.
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Affiliation(s)
- Alexia Plocque
- Medical and Surgical Intensive Care Unit, Groupe Hospitalier Paris Saint Joseph, Paris, France
| | - Christie Mitri
- Centre de Recherche Saint-Antoine, CRSA, Sorbonne Université, Inserm, 75012, Paris, France
| | - Charlène Lefèvre
- Medical and Surgical Intensive Care Unit, Groupe Hospitalier Paris Saint Joseph, Paris, France
| | - Olivier Tabary
- Centre de Recherche Saint-Antoine, CRSA, Sorbonne Université, Inserm, 75012, Paris, France
| | - Lhousseine Touqui
- INSERM U938 Unit, St. Antoine Research Centre, Sorbona University, Paris, France
- Mucoviscidosis and Pulmonary Disease Units, Institute Pasteur, Paris, France
- Cystic fibrosis and Bronchial diseases team-INSERM U938, Institut Pasteur, Paris, France
| | - Francois Philippart
- Medical and Surgical Intensive Care Unit, Groupe Hospitalier Paris Saint Joseph, Paris, France.
- Endotoxins, Structures and Host Response, Department of Microbiology, Institute for Integrative Biology of the Cell, UMR 9891 CNRS-CEA-Paris Saclay University, 98190, Gif-sur-Yvette, France.
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18
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Donohue KN, Sivanushanthan S, Etling E, Hockstein M, Yohannes S, Clark P. Incidence of barotrauma in patients with COVID-19 (alpha- and beta-predominant period) requiring mechanical ventilation: Single-center retrospective study. SAGE Open Med 2023; 11:20503121231159479. [PMID: 36941897 PMCID: PMC10020859 DOI: 10.1177/20503121231159479] [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: 10/12/2022] [Accepted: 02/07/2023] [Indexed: 03/18/2023] Open
Abstract
Objective We sought to determine predictors, incidence, and interventions required for patients who developed barotrauma. Pneumothorax, subcutaneous emphysema, and pneumomediastinum have all been reported as complications related to COVID-19-positive patients requiring invasive mechanical ventilation. Methods In this retrospective study, clinical and imaging data from COVID-19 patients were collected and reviewed by two independent intensivists between January 4, 2020 and January 10, 2020. Data were used to identify COVID-19-positive patients requiring invasive mechanical ventilation and the incidence of barotrauma. Two separate cohorts were created as non-injured (no barotrauma) and injured (barotrauma present). We then sought to identify the risk factors for barotrauma in the non-injured cohort on Days 0, 7, 10, and 14 after intubation and day of injury in the injured cohort. Results Of the 264 patients with COVID-19, 55.8% were African American. The non-injured group was older (60 ± 15 versus 49 ± 16, p = 0.006), with male predominance in the injured group versus non-injured group (75% versus 55%). A total of 16 (6.5%) patients developed one or more complications of barotrauma, defined as subcutaneous emphysema, pneumothorax, or pneumomediastinum. Length of stay was longer for the injured group versus non-injured group (47 versus 25 days). Plateau pressure (p = 0.024), fraction of inspired oxygen (p < 0.001), and driving pressure (p = 0.001) were statistically significant in injured cohort. Mortality rate in non-injured versus injured was 49.4% versus 69%. Using random effect model, fraction of inspired oxygen (p = 0.003) and mean airway pressure (p = 0.010) were significant at the time of injury. When comparing alive versus deceased in the injured cohort, thoracostomy placement in alive versus deceased was 80% versus 54.5%. Conclusion COVID acute respiratory distress syndrome patients requiring invasive mechanical ventilation had a higher rate of barotrauma and were younger than those who did not develop barotrauma. Possible interventions to be considered to decrease barotrauma are decreased driving pressure goal and universal use of esophageal balloon manometry.
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Affiliation(s)
| | | | - Emily Etling
- Georgetown University School of
Medicine, Washington, DC, USA
| | - Michael Hockstein
- Department of Critical Care, MedStar
Washington Hospital Center, Washington, DC, USA
| | - Seife Yohannes
- Department of Critical Care, MedStar
Washington Hospital Center, Washington, DC, USA
| | - Paul Clark
- Department of Critical Care, MedStar
Washington Hospital Center, Washington, DC, USA
- Paul Clark, Department of Critical Care,
Medstar Washington Hospital Center, 110 Irving St NW, Washington, DC 20010, USA.
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19
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Dey S, Murmu N, Mondal T, Saha I, Chatterjee S, Manna R, Haldar S, Dash SK, Sarkar TR, Giri B. Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection. Biomed Pharmacother 2022; 156:113801. [DOI: 10.1016/j.biopha.2022.113801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/29/2022] [Accepted: 10/02/2022] [Indexed: 11/30/2022] Open
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20
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Axelerad A, Stuparu AZ, Muja LF, Docu Axelerad S, Petrov SG, Gogu AE, Jianu DC. Narrative Review of New Insight into the Influence of the COVID-19 Pandemic on Cardiovascular Care. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1554. [PMID: 36363511 PMCID: PMC9694465 DOI: 10.3390/medicina58111554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 09/10/2024]
Abstract
Background and Objectives: The purpose of this paper was to perform a literature review on the effects of the COVID-19 pandemic on cardiothoracic and vascular surgery care and departments. Materials and Methods: To conduct this evaluation, an electronic search of many databases was conducted, and the resulting papers were chosen and evaluated. Results: Firstly, we have addressed the impact of COVID-19 infection on the cardiovascular system from the pathophysiological and treatment points of view. Afterwards, we analyzed every cardiovascular disease that seemed to appear after a COVID-19 infection, emphasizing the treatment. In addition, we have analyzed the impact of the pandemic on the cardiothoracic and vascular departments in different countries and the transitions that appeared. Finally, we discussed the implications of the cardiothoracic and vascular specialists' and residents' work and studies on the pandemic. Conclusions: The global pandemic caused by SARS-CoV-2 compelled the vascular profession to review the treatment of certain vascular illnesses and find solutions to address the vascular consequences of COVID-19 infection. The collaboration between vascular surgeons, public health specialists, and epidemiologists must continue to investigate the impact of the pandemic and the response to the public health issue.
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Affiliation(s)
- Any Axelerad
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Alina Zorina Stuparu
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Lavinia Florenta Muja
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | | | - Silvia Georgeta Petrov
- Doctoral School of the Faculty of Psychology and Educational Sciences within the University of Bucharest, 050663 Bucharest, Romania
| | - Anca Elena Gogu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Dragos Catalin Jianu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
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21
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Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses. Vaccines (Basel) 2022; 10:vaccines10111805. [DOI: 10.3390/vaccines10111805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/14/2022] [Accepted: 10/19/2022] [Indexed: 11/17/2022] Open
Abstract
The current century has witnessed infections of pandemic proportions caused by Coronaviruses (CoV) including severe acute respiratory syndrome-related CoV (SARS-CoV), Middle East respiratory syndrome-related CoV (MERS-CoV) and the recently identified SARS-CoV2. Significantly, the SARS-CoV2 outbreak, declared a pandemic in early 2020, has wreaked devastation and imposed intense pressure on medical establishments world-wide in a short time period by spreading at a rapid pace, resulting in high morbidity and mortality. Therefore, there is a compelling need to combat and contain the CoV infections. The current review addresses the unique features of the molecular virology of major Coronaviruses that may be tractable towards antiviral targeting and design of novel preventative and therapeutic intervention strategies. Plant-derived vaccines, in particular oral vaccines, afford safer, effectual and low-cost avenues to develop antivirals and fast response vaccines, requiring minimal infrastructure and trained personnel for vaccine administration in developing countries. This review article discusses recent developments in the generation of plant-based vaccines, therapeutic/drug molecules, monoclonal antibodies and phytochemicals to preclude and combat infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Efficacious plant-derived antivirals could contribute significantly to combating emerging and re-emerging pathogenic CoV infections and help stem the tide of any future pandemics.
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22
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Labarrere CA, Kassab GS. Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease. Front Microbiol 2022; 13:979719. [PMID: 36274722 PMCID: PMC9582773 DOI: 10.3389/fmicb.2022.979719] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/14/2022] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 19 (COVID-19) has numerous risk factors leading to severe disease with high mortality rate. Oxidative stress with excessive production of reactive oxygen species (ROS) that lower glutathione (GSH) levels seems to be a common pathway associated with the high COVID-19 mortality. GSH is a unique small but powerful molecule paramount for life. It sustains adequate redox cell signaling since a physiologic level of oxidative stress is fundamental for controlling life processes via redox signaling, but excessive oxidation causes cell and tissue damage. The water-soluble GSH tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) is present in the cytoplasm of all cells. GSH is at 1-10 mM concentrations in all mammalian tissues (highest concentration in liver) as the most abundant non-protein thiol that protects against excessive oxidative stress. Oxidative stress also activates the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) redox regulator pathway, releasing Nrf2 to regulate the expression of genes that control antioxidant, inflammatory and immune system responses, facilitating GSH activity. GSH exists in the thiol-reduced and disulfide-oxidized (GSSG) forms. Reduced GSH is the prevailing form accounting for >98% of total GSH. The concentrations of GSH and GSSG and their molar ratio are indicators of the functionality of the cell and its alteration is related to various human pathological processes including COVID-19. Oxidative stress plays a prominent role in SARS-CoV-2 infection following recognition of the viral S-protein by angiotensin converting enzyme-2 receptor and pattern recognition receptors like toll-like receptors 2 and 4, and activation of transcription factors like nuclear factor kappa B, that subsequently activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) expression succeeded by ROS production. GSH depletion may have a fundamental role in COVID-19 pathophysiology, host immune response and disease severity and mortality. Therapies enhancing GSH could become a cornerstone to reduce severity and fatal outcomes of COVID-19 disease and increasing GSH levels may prevent and subdue the disease. The life value of GSH makes for a paramount research field in biology and medicine and may be key against SARS-CoV-2 infection and COVID-19 disease.
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23
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Hilda F, Liana P, Nurtjahyo A, Hudari H, Purnama Sari N, Pratama Umar T, Alberto Amin C, Rahayu Afifah A. D-Dimer as a Sensitive Biomarker of Survival Rate in Patients with COVID-19. Eurasian J Med 2022; 54:219-224. [PMID: 35950823 PMCID: PMC9797773 DOI: 10.5152/eurasianjmed.2022.21145] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 08/12/2021] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE The global case fatality rate of coronavirus disease 2019 is 2.16% as announced by the World Health Organization. In Indonesia, according to the Ministry of Health, the number is even higher, reaching a 2.8% case fatality rate. D-dimer levels were found to affect coronavirus disease 2019 patient's survival in several studies. The study aimed to determine whether the amount of D-dimer predicted survival in coronavirus disease 2019 patients. MATERIALS AND METHODS This research was performed in a retrospective cohort design and used survival analysis. From March 1, 2020, to August 31, 2020, the samples were collected from polymerase chain reaction-confirmed coronavirus disease 2019 patients at Mohammad Hoesin General Hospital in Palembang, South Sumatera, Indonesia. We used electronic medical records to obtain demographic (age and gender), coexisting condition, laboratory (coagulation and hematologic test), and outcome (non-survivors or survivors) data. The chi-square and Mann-Whitney tests were used to evaluate the results. The Kaplan-Meier method and the Mantel-Haenszel log-rank test were used to examine D-dimer levels and patient outcomes. Youden index was calculated to determine the optimal cut-off value of D-dimer. RESULTS There were 52 non-survivors and 235 survivors among the 287 patients who met the inclusion criterion. Non-survivors had D-dimer levels of more than 1.49 mg/L in 82.69%of cases. Males had lower cut-off compared to females (>1.49 mg/L vs. >2.2 mg/L). The researchers discovered a highly significant correlation between D-dimer levels and coronavirus disease 2019 mortality (P=.001). The c-index analysis showed that D-dimer (0.79, 95% CI: 0.73-0.83) ability for mortality prediction was the second-best compared with other laboratory markers. CONCLUSION D-dimer can be used as a predictor of coronavirus disease 2019 in-hospital mortality for early identification of coagulopathy.
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Affiliation(s)
- Fadhilatul Hilda
- Medical Profession Program, Universitas Sriwijaya Faculty of Medicine, Palembang, Indonesia
| | - Phey Liana
- Department of Clinical Pathology, Universitas Sriwijaya – Mohammad Hoesin General Hospital, Palembang, Indonesia
- Biomedicine Doctoral Program, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia
| | - Awan Nurtjahyo
- Department of Obstetrics and Gynecology, Universitas Sriwijaya – Mohammad Hoesin General Hospital, Palembang, Indonesia
| | - Harun Hudari
- Department of Internal Medicine, Universitas Sriwijaya – Mohammad Hoesin General Hospital, Palembang, Indonesia
| | - Nurmalia Purnama Sari
- Department of Clinical Pathology, Universitas Sriwijaya – Mohammad Hoesin General Hospital, Palembang, Indonesia
| | - Tungki Pratama Umar
- Medical Profession Program, Universitas Sriwijaya Faculty of Medicine, Palembang, Indonesia
| | - Chris Alberto Amin
- Medical Profession Program, Universitas Sriwijaya Faculty of Medicine, Palembang, Indonesia
| | - Astari Rahayu Afifah
- Medical Profession Program, Universitas Sriwijaya Faculty of Medicine, Palembang, Indonesia
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24
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Wifi MN, Morad MA, El Sheemy R, Abdeen N, Afify S, Abdalgaber M, Abdellatef A, Zaghloul M, Alboraie M, El-Kassas M. Hemostatic system and COVID-19 crosstalk: A review of the available evidence. World J Methodol 2022; 12:331-349. [PMID: 36186748 PMCID: PMC9516549 DOI: 10.5662/wjm.v12.i5.331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 03/17/2022] [Accepted: 07/19/2022] [Indexed: 02/08/2023] Open
Abstract
Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.
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Affiliation(s)
- Mohamed-Naguib Wifi
- Department of Internal Medicine, Hepatogastro- enterology Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo 11451, Egypt
| | - Mohamed Abdelkader Morad
- Clinical Hematology Unit, Department of Internal Medicine, Kasr Al-Ainy, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
| | - Reem El Sheemy
- Department of Tropical Medicine, Minia Faculty of Medicine, Minia University, Minia 61511, Egypt
| | - Nermeen Abdeen
- Department of Tropical Medicine, Faculty of Medicine, Alexandria University, Alexandria 21523, Egypt
| | - Shimaa Afify
- Department of Gastroenterology, National Hepatology and Tropical Medicine, National Hepatology and Tropical Medicine Research Institute, Cairo 11451, Egypt
| | - Mohammad Abdalgaber
- Department of Gastroenterology and Hepatology, Police Authority Hospital, Agoza, Giza 12511, Egypt
| | - Abeer Abdellatef
- Department of Internal Medicine, Hepatogastro- enterology Unit, Kasr Al-Ainy School of Medicine, Cairo University, Cairo 11451, Egypt
| | - Mariam Zaghloul
- Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33511, Egypt
| | - Mohamed Alboraie
- Department of Internal Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Helwan 11731, Egypt
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25
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Bello-Perez M, Hurtado-Tamayo J, Requena-Platek R, Canton J, Sánchez-Cordón PJ, Fernandez-Delgado R, Enjuanes L, Sola I. MERS-CoV ORF4b is a virulence factor involved in the inflammatory pathology induced in the lungs of mice. PLoS Pathog 2022; 18:e1010834. [PMID: 36129908 PMCID: PMC9491562 DOI: 10.1371/journal.ppat.1010834] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 08/26/2022] [Indexed: 01/18/2023] Open
Abstract
No vaccines or specific antiviral drugs are authorized against Middle East respiratory syndrome coronavirus (MERS-CoV) despite its high mortality rate and prevalence in dromedary camels. Since 2012, MERS-CoV has been causing sporadic zoonotic infections in humans, which poses a risk of genetic evolution to become a pandemic virus. MERS-CoV genome encodes five accessory proteins, 3, 4a, 4b, 5 and 8b for which limited information is available in the context of infection. This work describes 4b as a virulence factor in vivo, since the deletion mutant of a mouse-adapted MERS-CoV-Δ4b (MERS-CoV-MA-Δ4b) was completely attenuated in a humanized DPP4 knock-in mouse model, resulting in no mortality. Attenuation in the absence of 4b was associated with a significant reduction in lung pathology and chemokine expression levels at 4 and 6 days post-infection, suggesting that 4b contributed to the induction of lung inflammatory pathology. The accumulation of 4b in the nucleus in vivo was not relevant to virulence, since deletion of its nuclear localization signal led to 100% mortality. Interestingly, the presence of 4b protein was found to regulate autophagy in the lungs of mice, leading to upregulation of BECN1, ATG3 and LC3A mRNA. Further analysis in MRC-5 cell line showed that, in the context of infection, MERS-CoV-MA 4b inhibited autophagy, as confirmed by the increase of p62 and the decrease of ULK1 protein levels, either by direct or indirect mechanisms. Together, these results correlated autophagy activation in the absence of 4b with downregulation of a pathogenic inflammatory response, thus contributing to attenuation of MERS-CoV-MA-Δ4b.
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Affiliation(s)
- Melissa Bello-Perez
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Jesús Hurtado-Tamayo
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Ricardo Requena-Platek
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Javier Canton
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Pedro José Sánchez-Cordón
- Veterinary Pathology Department, Animal Health Research Center (CISA), National Institute of Research, Agricultural and Food Technology (INIA-CSIC), Valdeolmos, Madrid, Spain
| | - Raúl Fernandez-Delgado
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Luis Enjuanes
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
| | - Isabel Sola
- Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin, Madrid, Spain
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26
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Patel N, Nicolae R, Geropoulos G, Mandal P, Christou CD, Gavala M, Madouros N, Papapanou M, Mogal R, Giannis D, Kechagias KS, Panagiotopoulos N. Pneumomediastinum in the COVID-19 era: to drain or not to drain? Monaldi Arch Chest Dis 2022; 93. [PMID: 35904103 DOI: 10.4081/monaldi.2022.2338] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 07/20/2022] [Indexed: 02/07/2023] Open
Abstract
Pneumomediastinum (PNM) is a rare clinical finding, usually with a benign course, which is managed conservatively in the majority of cases. However, during the COVID-19 pandemic, an increased incidence of PNM has been observed. Several reports of PNM cases in COVID-19 have been reported in the literature and were managed either conservatively or surgically. In this study, we present our institutional experience of COVID-19 associated PNM, propose a management algorithm, and review the current literature. In total, 43 Case Series were identified, including a total of 747 patients, of whom 374/747 (50.1%) were intubated at the time of diagnosis, 168/747 (22.5%) underwent surgical drain insertion at admission, 562/747 (75.2%) received conservative treatment (observation or mechanical ventilation. Inpatient mortality was 51.8% (387/747), while 45.1% of the population recovered and/or was discharged (337/747). In conclusion, with increased incidence of PNM in COVID-19 patients reported in the literature, it is still difficult to assign a true causal relationship between PNM and mortality. We can, however, see that PMN plays an important role in disease prognosis. Due to increased complexity, high mortality, and associated complications, conservative management may not be sufficient, and a surgical approach is needed.
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Affiliation(s)
- Nian Patel
- Department of General Surgery, University College London Hospitals, NHS Foundation Trust, London.
| | - Robert Nicolae
- Surgery Working Group, Society of Junior Doctors, Athens, Greece.
| | - Georgios Geropoulos
- Thoracic Surgery Department, University College London Hospitals, NHS Foundation Trust, London.
| | - Pallabhi Mandal
- Department of General Surgery, University College London Hospitals, NHS Foundation Trust, London.
| | | | | | | | | | - Rahul Mogal
- Respiratory Medicine Department, Watford General Hospital, West Hertfordshire Hospitals, NHS Foundation Trust, Hertfordshire.
| | | | - Konstantinos S Kechagias
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London.
| | - Nikolaos Panagiotopoulos
- Thoracic Surgery Department, University College London Hospitals, NHS Foundation Trust, London, UK..
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27
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Singh S, Weiss A, Goodman J, Fisk M, Kulkarni S, Lu I, Gray J, Smith R, Sommer M, Cheriyan J. Niclosamide-A promising treatment for COVID-19. Br J Pharmacol 2022; 179:3250-3267. [PMID: 35348204 PMCID: PMC9111792 DOI: 10.1111/bph.15843] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 01/09/2022] [Accepted: 02/23/2022] [Indexed: 12/15/2022] Open
Abstract
Vaccines have reduced the transmission and severity of COVID-19, but there remains a paucity of efficacious treatment for drug-resistant strains and more susceptible individuals, particularly those who mount a suboptimal vaccine response, either due to underlying health conditions or concomitant therapies. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics, such as COVID-19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth already in human use as a treatment for COVID-19. In addition, its potent antiviral activity, niclosamide has shown pleiotropic anti-inflammatory, antibacterial, bronchodilatory and anticancer effects in numerous preclinical and early clinical studies. The advantages and rationale for nebulized and intranasal formulations of niclosamide, which target the site of the primary infection in COVID-19, are reviewed. Finally, we give an overview of ongoing clinical trials investigating niclosamide as a promising candidate against SARS-CoV-2.
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Affiliation(s)
- Shivani Singh
- Division of Pulmonary and Critical Care MedicineNYU School of MedicineNew YorkNew YorkUSA
| | - Anne Weiss
- Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkKongens LyngbyDenmark
- UNION Therapeutics Research ServicesHellerupDenmark
| | - James Goodman
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Marie Fisk
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Spoorthy Kulkarni
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Ing Lu
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Joanna Gray
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Rona Smith
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
- Cambridge Clinical Trials UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
| | - Morten Sommer
- Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkKongens LyngbyDenmark
- UNION TherapeuticsHellerupDenmark
| | - Joseph Cheriyan
- Department of MedicineCambridge University Hospitals NHS Foundation TrustCambridgeUK
- Cambridge Clinical Trials UnitCambridge University Hospitals NHS Foundation TrustCambridgeUK
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Kashani NR, Azadbakht J, Ehteram H, Kashani HH, Rajabi-Moghadam H, Ahmad E, Nikzad H, Hosseini ES. Molecular and Clinical Investigation of COVID-19: From Pathogenesis and Immune Responses to Novel Diagnosis and Treatment. Front Mol Biosci 2022; 9:770775. [PMID: 35664675 PMCID: PMC9161360 DOI: 10.3389/fmolb.2022.770775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Accepted: 04/04/2022] [Indexed: 01/08/2023] Open
Abstract
The coronavirus-related severe acute respiratory syndrome (SARS-CoV) in 2002/2003, the Middle East respiratory syndrome (MERS-CoV) in 2012/2013, and especially the current 2019/2021 severe acute respiratory syndrome-2 (SARS-CoV-2) negatively affected the national health systems worldwide. Different SARS-CoV-2 variants, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and recently Omicron (B.1.1.529), have emerged resulting from the high rate of genetic recombination and S1-RBD/S2 mutation/deletion in the spike protein that has an impact on the virus activity. Furthermore, genetic variability in certain genes involved in the immune system might impact the level of SARS-CoV-2 recognition and immune response against the virus among different populations. Understanding the molecular mechanism and function of SARS-CoV-2 variants and their different epidemiological outcomes is a key step for effective COVID-19 treatment strategies, including antiviral drug development and vaccine designs, which can immunize people with genetic variabilities against various strains of SARS-CoV-2. In this review, we center our focus on the recent and up-to-date knowledge on SARS-CoV-2 (Alpha to Omicron) origin and evolution, structure, genetic diversity, route of transmission, pathogenesis, new diagnostic, and treatment strategies, as well as the psychological and economic impact of COVID-19 pandemic on individuals and their lives around the world.
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Affiliation(s)
- Narjes Riahi Kashani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Javid Azadbakht
- Department of Radiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hassan Ehteram
- Department of Pathology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Haddad Kashani
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Hassan Rajabi-Moghadam
- Department of Cardiovascular Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Ejaz Ahmad
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Hossein Nikzad
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
| | - Elahe Seyed Hosseini
- Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran
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Karunakaran KB, Balakrishnan N, Ganapathiraju MK. Interactome of SARS-CoV-2 Modulated Host Proteins With Computationally Predicted PPIs: Insights From Translational Systems Biology Studies. FRONTIERS IN SYSTEMS BIOLOGY 2022; 2. [DOI: 10.3389/fsysb.2022.815237] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Accelerated efforts to identify intervention strategies for the COVID-19 pandemic caused by SARS-CoV-2 need to be supported by deeper investigations into host invasion and response mechanisms. We constructed the neighborhood interactome network of the 332 human proteins targeted by SARS-CoV-2 proteins, augmenting it with 1,941 novel human protein-protein interactions predicted using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. Novel interactors, and the interactome as a whole, showed significant enrichment for genes differentially expressed in SARS-CoV-2-infected A549 and Calu-3 cells, postmortem lung samples of COVID-19 patients and blood samples of COVID-19 patients with severe clinical outcomes. The PPIs connected host proteins to COVID-19 blood biomarkers, ACE2 (SARS-CoV-2 entry receptor), genes differentiating SARS-CoV-2 infection from other respiratory virus infections, and SARS-CoV-targeted host proteins. Novel PPIs facilitated identification of the cilium organization functional module; we deduced the potential antiviral role of an interaction between the virus-targeted NUP98 and the cilia-associated CHMP5. Functional enrichment analyses revealed promyelocytic leukaemia bodies, midbody, cell cycle checkpoints and tristetraprolin pathway as potential viral targets. Network proximity of diabetes and hypertension associated genes to host proteins indicated a mechanistic basis for these co-morbidities in critically ill/non-surviving patients. Twenty-four drugs were identified using comparative transcriptome analysis, which include those undergoing COVID-19 clinical trials, showing broad-spectrum antiviral properties or proven activity against SARS-CoV-2 or SARS-CoV/MERS-CoV in cell-based assays. The interactome is available on a webserver at http://severus.dbmi.pitt.edu/corona/.
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Soni R, Brewster W, Weeks W, Graves S. A Unique Presentation of Spontaneous Pneumomediastinum Following COVID-19 Infection. Cureus 2022; 14:e24565. [PMID: 35651375 PMCID: PMC9138616 DOI: 10.7759/cureus.24565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2022] [Indexed: 11/18/2022] Open
Abstract
Pneumomediastinum is a rare, life-threatening condition in which air leaks into the mediastinum. Usually, it results from a traumatic event that leads to the escape of air from the airway, lungs, or bowel into the chest cavity. Patients with underlying lung pathology or a history of invasive mechanical ventilation have an increased risk of developing a pneumomediastinum. A spontaneous pneumomediastinum (SPM) occurs in the absence of these risk factors. Patients with coronavirus disease 2019 (COVID-19) pneumonia tend to have a higher risk of developing an SPM, however, this is usually linked to mechanical ventilator use. Although rare, cases of healthy young patients with no history of underlying lung pathology or mechanical ventilator use developing an SPM are increasingly being reported. In efforts to bring more attention to this complication, we present the case of an SPM in a 40-year-old female patient with COVID-19 pneumonia and highlight the importance of close follow-up.
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Morrison CB, Edwards CE, Shaffer KM, Araba KC, Wykoff JA, Williams DR, Asakura T, Dang H, Morton LC, Gilmore RC, O’Neal WK, Boucher RC, Baric RS, Ehre C. SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13. Proc Natl Acad Sci U S A 2022; 119:e2119680119. [PMID: 35353667 PMCID: PMC9169748 DOI: 10.1073/pnas.2119680119] [Citation(s) in RCA: 68] [Impact Index Per Article: 22.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/14/2022] [Indexed: 12/15/2022] Open
Abstract
Muco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host–virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection. Electron microscopy identified intense viral egress from infected ciliated cells and severe cytopathogenesis, culminating in the shedding of ciliated cells packed with virions, providing a large viral reservoir for spread and transmission. Intracellular stores of MUC5AC, a major airway mucin involved in asthma, were rapidly depleted, likely to trap viruses. To mimic asthmatic airways, HAE cells were treated with interleukin-13 (IL-13), which reduced viral titers, viral messenger RNA, and cell shedding, and significantly diminished the number of infected cells. Although mucus hyperproduction played a shielding role, IL-13–treated cells maintained a degree of protection despite the removal of mucus. Using Gene Expression Omnibus databases, bulk RNA-sequencing analyses revealed that IL-13 up-regulated genes controlling glycoprotein synthesis, ion transport, and antiviral processes (albeit not the typical interferon-induced genes) and down-regulated genes involved in cilial function and ribosomal processing. More precisely, we showed that IL-13 reduced ACE2 expression, intracellular viral load, and cell-to-cell transmission while increasing the cilial keratan sulfate coating. In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread.
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Affiliation(s)
- Cameron B. Morrison
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Caitlin E. Edwards
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Kendall M. Shaffer
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Kenza C. Araba
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Jason A. Wykoff
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Danielle R. Williams
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Takanori Asakura
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Hong Dang
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Lisa C. Morton
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Rodney C. Gilmore
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Wanda K. O’Neal
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Richard C. Boucher
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Ralph S. Baric
- Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
| | - Camille Ehre
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
- Department of Pediatrics/Pediatric Pulmonology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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Al-Tamimi AO, Yusuf AM, Jayakumar MN, Ansari AW, Elhassan M, AbdulKarim F, Kannan M, Halwani R, Ahmad F. SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19. Int J Lab Hematol 2022; 44:712-721. [PMID: 35266284 PMCID: PMC9111479 DOI: 10.1111/ijlh.13829] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 01/29/2022] [Accepted: 03/02/2022] [Indexed: 01/08/2023]
Abstract
Introduction Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID‐19. However, it is unclear when particularly platelet activation markers and coagulation factors dysregulated during the pathogenesis of COVID‐19. Here, we sought to assess the levels of coagulation and platelet activation markers at moderate and severe stages of COVID‐19 to understand the pathogenesis. Methods To understand this, hospitalized COVID‐19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases) were recruited. Phenotypic and molecular characterizations were performed employing basic coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), D‐Dimer, and tissue factor pathway inhibitor (TFPI). The flow cytometry‐based multiplex assays were performed to assess FXI, anti‐thrombin, prothrombin, fibrinogen, FXIII, P‐selectin, sCD40L, plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor‐1 (PAI‐1), and D‐Dimer. Results The investigations revealed induction of plasma P‐selectin and CD40 ligand (sCD40L) in moderate COVID‐19 cases, which were significantly abolished with the progression of COVID‐19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID‐19. Further analysis revealed fibrinogen induction in both moderate and severe patients. Interestingly, an elevated PAI‐1 more prominently in moderate, and tPA particularly in severe COVID‐19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of the disease. Conclusions In summary, induction of soluble P‐selectin, sCD40L, fibrinogen, and PAI‐1 suggests the activation of platelets and coagulation system at the moderate stage before COVID‐19 patients require intensive care. These findings would help in designing better thromboprophylaxis to limit the COVID‐19 severity.
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Affiliation(s)
- Abaher O Al-Tamimi
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
| | - Ayesha M Yusuf
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
| | - Manju N Jayakumar
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE
| | - Abdul W Ansari
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE.,Dermatology Institute, Translational Research Institute, Academic Health Systems, Hamad Medical Corporation, Doha, Qatar
| | - Mona Elhassan
- Department of Internal Medicine, Rashid Hospital, Dubai, UAE
| | | | - Meganathan Kannan
- Blood and Vascular Biology Research Lab, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India
| | - Rabih Halwani
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE
| | - Firdos Ahmad
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, UAE.,Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE
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Chimenti C, Magnocavallo M, Ballatore F, Bernardini F, Alfarano M, Della Rocca DG, Severino P, Lavalle C, Francesco F, Frustaci A. Prevalence and Clinical Implications of COVID-19 Myocarditis. Card Electrophysiol Clin 2022; 14:53-62. [PMID: 35221085 PMCID: PMC8576114 DOI: 10.1016/j.ccep.2021.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The clinical manifestations of COVID-19 are widely variable and may involve several districts. Although the clinical course is mostly characterized by respiratory involvement, up to 30% of hospitalized patients have evidence of myocardial injury due to acute coronary syndrome, cardiac arrhythmias, myocarditis, and cardiogenic shock. In particular, myocarditis is a well-recognized severe complication of COVID-19 and is associated with fulminant cardiogenic shock and sudden cardiac death. In this article, the authors aim to present a comprehensive review about COVID-19-related myocarditis, including clinical characteristics, diagnostic workup, and management.
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Affiliation(s)
- Cristina Chimenti
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome 00149, Italy.
| | - Michele Magnocavallo
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Federico Ballatore
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Federico Bernardini
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Maria Alfarano
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Domenico G Della Rocca
- Texas Cardiac Arrhythmia Institute, St. David's Medical Center, 3000 North IH-35, Suite 720, Austin, TX 78705, USA
| | - Paolo Severino
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Carlo Lavalle
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Fedele Francesco
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
| | - Andrea Frustaci
- Department of Cardiovascular/Respiratory Diseases, Nephrology, Anesthesiology, and Geriatric Sciences, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome 00149, Italy
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Sampieri CL, Montero H. [Review of new evidence about the possible vertical transmission of coronavirus disease-2019]. GACETA SANITARIA 2022; 36:166-172. [PMID: 32711871 PMCID: PMC7305917 DOI: 10.1016/j.gaceta.2020.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 06/03/2020] [Accepted: 06/15/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To conduct a systematic review of original peer-reviewed studies, containing data on the identification of SARS-CoV-2 in clinical samples of amniotic fluid, placenta or membranes, umbilical cord blood, and human milk, from women with a clinically or confirmed diagnosis of COVID-19. These studies should have been published after the guide for the management of patients with COVID-19 from World Health Organization guide (available in March 13, 2020). RESULTS Seventeen studies were included, in which 143 clinical samples were identified (38 of amniotic fluid; 34 of placentas or membranes; 39 from umbilical cord blood and 32 from human milk). Among the 143 samples, nine were positive for SARS-CoV-2 RNA (one amniotic fluid sample obtained before rupturing the membranes; six samples of placenta or membranes, although authors indicate the possibility of contamination by maternal blood in three of these, and two samples of human milk). CONCLUSIONS Following our search criteria, we found no studies that demonstrate the detection of SARS-CoV-2, in conjunction with viral isolation and the evaluation of the infective capacity of viral particles, in clinical samples of amniotic fluid, placenta or membranes, umbilical cord blood and human milk, from women with a confirmed or clinical diagnosis of COVID-19. However, vertical transmission cannot be ruled out, larger studies are required that ideally locate in situ RNA and protein of SARS-CoV-2, as well as isolation that demonstrate the infective capacity of the viral particles.
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Affiliation(s)
- Clara Luz Sampieri
- Instituto de Salud Pública, Universidad Veracruzana, Xalapa, Veracruz, México.
| | - Hilda Montero
- Instituto de Salud Pública, Universidad Veracruzana, Xalapa, Veracruz, México
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Ortega-Peña S, Rodríguez-Martínez S, Cancino-Diaz ME, Cancino-Diaz JC. Staphylococcus epidermidis Controls Opportunistic Pathogens in the Nose, Could It Help to Regulate SARS-CoV-2 (COVID-19) Infection? Life (Basel) 2022; 12:341. [PMID: 35330092 PMCID: PMC8954679 DOI: 10.3390/life12030341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023] Open
Abstract
Staphylococcus epidermidis is more abundant in the anterior nares than internal parts of the nose, but its relative abundance changes along with age; it is more abundant in adolescents than in children and adults. Various studies have shown that S. epidermidis is the guardian of the nasal cavity because it prevents the colonization and infection of respiratory pathogens (bacteria and viruses) through the secretion of antimicrobial molecules and inhibitors of biofilm formation, occupying the space of the membrane mucosa and through the stimulation of the host's innate and adaptive immunity. There is a strong relationship between the low number of S. epidermidis in the nasal cavity and the increased risk of serious respiratory infections. The direct application of S. epidermidis into the nasal cavity could be an effective therapeutic strategy to prevent respiratory infections and to restore nasal cavity homeostasis. This review shows the mechanisms that S. epidermidis uses to eliminate respiratory pathogens from the nasal cavity, also S. epidermidis is proposed to be used as a probiotic to prevent the development of COVID-19 because S. epidermidis induces the production of interferon type I and III and decreases the expression of the entry receptors of SARS-CoV-2 (ACE2 and TMPRSS2) in the nasal epithelial cells.
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Affiliation(s)
- Silvestre Ortega-Peña
- Laboratorio Tejido Conjuntivo, Centro Nacional de Investigación y Atención de Quemados, Instituto Nacional de Rehabilitación “Luís Guillermo Ibarra Ibarra”, Ciudad de México 14389, Mexico
| | - Sandra Rodríguez-Martínez
- Laboratorio de Inmunidad Innata, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (S.R.-M.); (M.E.C.-D.)
| | - Mario E. Cancino-Diaz
- Laboratorio de Inmunidad Innata, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico; (S.R.-M.); (M.E.C.-D.)
| | - Juan C. Cancino-Diaz
- Laboratorio de Inmunomicrobiología, Departamento Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico
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Kircher M, Chludzinski E, Krepel J, Saremi B, Beineke A, Jung K. Augmentation of Transcriptomic Data for Improved Classification of Patients with Respiratory Diseases of Viral Origin. Int J Mol Sci 2022; 23:ijms23052481. [PMID: 35269624 PMCID: PMC8910329 DOI: 10.3390/ijms23052481] [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: 11/25/2021] [Revised: 02/17/2022] [Accepted: 02/21/2022] [Indexed: 02/01/2023] Open
Abstract
To better understand the molecular basis of respiratory diseases of viral origin, high-throughput gene-expression data are frequently taken by means of DNA microarray or RNA-seq technology. Such data can also be useful to classify infected individuals by molecular signatures in the form of machine-learning models with genes as predictor variables. Early diagnosis of patients by molecular signatures could also contribute to better treatments. An approach that has rarely been considered for machine-learning models in the context of transcriptomics is data augmentation. For other data types it has been shown that augmentation can improve classification accuracy and prevent overfitting. Here, we compare three strategies for data augmentation of DNA microarray and RNA-seq data from two selected studies on respiratory diseases of viral origin. The first study involves samples of patients with either viral or bacterial origin of the respiratory disease, the second study involves patients with either SARS-CoV-2 or another respiratory virus as disease origin. Specifically, we reanalyze these public datasets to study whether patient classification by transcriptomic signatures can be improved when adding artificial data for training of the machine-learning models. Our comparison reveals that augmentation of transcriptomic data can improve the classification accuracy and that fewer genes are necessary as explanatory variables in the final models. We also report genes from our signatures that overlap with signatures presented in the original publications of our example data. Due to strict selection criteria, the molecular role of these genes in the context of respiratory infectious diseases is underlined.
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Affiliation(s)
- Magdalena Kircher
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Buenteweg 17p, 30559 Hannover, Germany; (M.K.); (J.K.); (B.S.)
| | - Elisa Chludzinski
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany; (E.C.); (A.B.)
| | - Jessica Krepel
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Buenteweg 17p, 30559 Hannover, Germany; (M.K.); (J.K.); (B.S.)
| | - Babak Saremi
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Buenteweg 17p, 30559 Hannover, Germany; (M.K.); (J.K.); (B.S.)
| | - Andreas Beineke
- Department of Pathology, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany; (E.C.); (A.B.)
| | - Klaus Jung
- Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Buenteweg 17p, 30559 Hannover, Germany; (M.K.); (J.K.); (B.S.)
- Correspondence: ; Tel.: +49-511-953-8878
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Gauthier T, Chen W. Modulation of Macrophage Immunometabolism: A New Approach to Fight Infections. Front Immunol 2022; 13:780839. [PMID: 35154105 PMCID: PMC8825490 DOI: 10.3389/fimmu.2022.780839] [Citation(s) in RCA: 61] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 01/07/2022] [Indexed: 12/13/2022] Open
Abstract
Macrophages are essential innate immune cells that contribute to host defense during infection. An important feature of macrophages is their ability to respond to extracellular cues and to adopt different phenotypes and functions in response to these stimuli. The evidence accumulated in the last decade has highlighted the crucial role of metabolic reprogramming during macrophage activation in infectious context. Thus, understanding and manipulation of macrophage immunometabolism during infection could be of interest to develop therapeutic strategies. In this review, we focus on 5 major metabolic pathways including glycolysis, pentose phosphate pathway, fatty acid oxidation and synthesis, tricarboxylic acid cycle and amino acid metabolism and discuss how they sustain and regulate macrophage immune function in response to parasitic, bacterial and viral infections as well as trained immunity. At the end, we assess whether some drugs including those used in clinic and in development can target macrophage immunometabolism for potential therapy during infection with an emphasis on SARS-CoV2 infection.
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Affiliation(s)
- Thierry Gauthier
- Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, United States
| | - Wanjun Chen
- Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, United States
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Clayton E, Rohaim MA, Bayoumi M, Munir M. The Molecular Virology of Coronaviruses with Special Reference to SARS-CoV-2. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1352:15-31. [PMID: 35132592 DOI: 10.1007/978-3-030-85109-5_2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Coronaviruses (CoVs) are large, enveloped and positive-sense RNA viruses which are responsible for a range of upper respiratory and digestive tract infections. Interest in coronaviruses has recently escalated due to the identification of a newly emerged coronavirus named severe acute respiratory syndrome 2 (SARS-CoV-2), which is the causative agent of the COVID-19 pandemic. In this chapter, we summarise molecular virological features of coronaviruses and understand their molecular mechanisms of replication in guiding the control of the global COVID-19 pandemic. METHODS We applied a holistic and comparative approach to assess the current understanding of coronavirus molecular virology and identify research gaps among different human coronaviruses. RESULTS Coronaviruses can utilise unique strategies that aid in their pathogenicity, replication and survival in multiple hosts. Replication of coronaviruses involves novel mechanisms such as ribosomal frameshifting and the synthesis of both genomic and sub-genomic RNAs. We summarised the key components in coronavirus molecular biology and molecular determinants of pathogenesis. Focusing largely on SARS-CoV-2 due to its current importance, this review explores the virology of recently emerged coronaviruses to gain an in-depth understanding of these infectious diseases. CONCLUSIONS The presented information provides fundamental bottlenecks to devise future disease control and management strategies to curtail the impact of coronaviruses in human populations.
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Affiliation(s)
- Emily Clayton
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK
| | - Mohammed A Rohaim
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK
| | - Mahmoud Bayoumi
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK
| | - Muhammad Munir
- Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
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Ahmad F, Kannan M, Ansari AW. Role of SARS-CoV-2 -induced cytokines and growth factors in coagulopathy and thromboembolism. Cytokine Growth Factor Rev 2022; 63:58-68. [PMID: 34750061 PMCID: PMC8541834 DOI: 10.1016/j.cytogfr.2021.10.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 01/08/2023]
Abstract
Severe COVID-19 patients frequently present thrombotic complications which commonly lead to multiorgan failure and increase the risk of death. Severe SARS-CoV-2 infection induces the cytokine storm and is often associated with coagulation dysfunction. D-dimer, a hallmark of venous thromboembolism (VTE), is observed at a higher level in the majority of hospitalized COVID-19 patients. The precise molecular mechanism of the disproportionate effect of SARS-CoV-2 infection on the coagulation system is largely undefined. SARS-CoV-2 -induced endotheliopathy and, induction of cytokines and growth factors (GFs) most likely play important roles in platelet activation, coagulopathy, and VTE. Generally, viral infections lead to systemic inflammation and induction of numerous cytokines and GFs and many of them are reported to be associated with increased VTE. Most importantly, platelets play key thromboinflammatory roles linking coagulation to immune mediators in a variety of infections including response to viral infection. Since the pathomechanism of coagulopathy and VTE in COVID-19 is largely undefined, herein we highlight the association of dysregulated inflammatory cytokines and GFs with thrombotic complications and coagulopathy in COVID-19.
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Affiliation(s)
- Firdos Ahmad
- College of Medicine, University of Sharjah, Sharjah 27272, UAE; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE.
| | - Meganathan Kannan
- Blood and Vascular Biology Research Lab, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur 610005, India
| | - Abdul W Ansari
- Dermatology Institute, Translational Research Institute, Academic Health Systems, Hamad Medical Corporation, PO Box 3050, Doha, Qatar
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Joishy SK, Sadohara M, Kurihara M, Tokuda Y. Complexity of the Diagnosis of COVID-19 in the Context of Pandemicity: Need for Excellence in Diagnostic Acumen. Korean J Fam Med 2022; 43:16-26. [PMID: 35130636 PMCID: PMC8820973 DOI: 10.4082/kjfm.20.0188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/02/2020] [Indexed: 12/03/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a highly infectious disease that has caused a pandemic devastating many countries worldwide. It is a complex and multifaceted disease with a unique coronavirus etiology, pathogenesis, zoonotic, and human-to-human transmission, causing acute respiratory distress syndrome with high mortality. Accurate and timely diagnosis is of utmost importance. In this study, we discussed the complexities of COVID-19 diagnostic elements in the context of pandemicity, drawing from our awareness, observations, and lessons learned from two previous coronavirus pandemics, namely SARS-CoV (severe acute respiratory syndrome coronavirus) in 2002 and MERS-CoV (Middle East respiratory syndrome-related coronavirus) in 2012, and how they applied to the diagnosis of COVID-19 today. Diagnosis of COVID-19 takes place without physician-patient personal contact due to isolation or quarantine or in the hospital setting, emergency units, and critical care units with the cumbersome barriers of personal protective equipment. Technical diagnosis is important, but we also emphasized the human impact of diagnosing COVID-19. Conveying the diagnosis of a critical disease to patients and families requires aspects of excellence in professionalism: ethics, empathy, and humility. Diagnostic skills in COVID-19 should extend to prognostication for patients suffering at the end of life, so that they will not be deprived of high-quality palliative care and comfort.
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Affiliation(s)
- Suresh K Joishy
- Former Medical Staff, Veterans Health Administration Hospital, Salt Lake City, UT, USA
| | - Michito Sadohara
- Department of Medical Education, Kumamoto University Hospital, Kumamoto, Japan
| | - Masaru Kurihara
- Department of Hospital Medicine, Urasoe General Hospital, Urasoe, Japan
| | - Yasuharu Tokuda
- Department of Medicine, Muribushi Okinawa Center for Teaching Hospitals, Urasoe, Japan
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Promising Effects of 3-Month Period of Quercetin Phytosome ® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study. Life (Basel) 2022; 12:life12010066. [PMID: 35054459 PMCID: PMC8780248 DOI: 10.3390/life12010066] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/23/2021] [Accepted: 01/02/2022] [Indexed: 12/13/2022] Open
Abstract
Quercetin, for its crucial properties, fulfills the need for a multifactor action that is useful for the potential counterbalance of a COVID-19 infection. Given this background, the aim of the study was to evaluate the potential effect of 3 months’ supplementation with Quercetin Phytosome® (250 mg twice a day) as prevention against symptomatic COVID-19. In total, 120 subjects were enrolled (males, 63; females, 57; age 49 ± 12), with 60 in the supplementation group and 60 in the placebo group. No significant differences were detected between groups in terms of gender, smoking, and chronic disease. Subjects underwent rapid COVID-19 diagnostic tests every 3 weeks. During our study, 5 subjects had COVID-19, 1 out of 60 subjects in the quercetin group and 4 out of 60 in the control group. Complete clinical remission was recorded at 7 and 15 days in the quercetin and placebo groups, respectively. Analysis showed that, at 5 months, the COVID free survival function (risk of infection) was 99.8% in subjects under quercetin supplementation and 96.5% in control group. As shown by the value of EXP(B), those who had taken the supplement had a protection factor of 14% more to not contract the COVID-19 infection than that of those who had taken a placebo. Obtained results are encouraging, but further studies are required to add quercetin as regular prophylaxis.
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The role of microRNAs in COVID-19 with a focus on miR-200c. J Circ Biomark 2022; 11:14-23. [PMID: 35356072 PMCID: PMC8939267 DOI: 10.33393/jcb.2022.2356] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 02/22/2022] [Indexed: 12/11/2022] Open
Abstract
Objective: Epigenetics is a quickly spreading scientific field, and the study of epigenetic regulation in various diseases such as infectious diseases is emerging. The microribonucleic acids (miRNAs) as one of the types of epigenetic processes bind to their target messenger RNAs (mRNAs) and regulate their stability and/or translation. This study aims to evaluate non-coding RNAs (ncRNAs) with a focus on miR-200c in COVID-19. In this review, we first define the epigenetics and miRNAs, and then the role of miRNAs in diseases focusing on lung diseases is explained. Finally, in this study, we will investigate the role and position of miRNAs with a focus on miR-200c in viral and severe acute respiratory syndrome–related coronavirus (SARS-CoV2) infections. Methods: Systematic search of MEDLINE, PubMed, Web of Science, Embase, and Cochrane Library was conducted for all relative papers from 2000 to 2021 with the limitations of the English language. Finally, we selected 128 articles which fit the best to our objective of study, among which 5 articles focused on the impact of miR-200c. Results: Due to the therapeutic results of various drugs in different races and populations, epigenetic processes, especially miRNAs, are important. The overall results showed that different types of miRNAs can be effective on the process of various lung diseases through different target pathways and genes. It is likely that amplified levels of miR-200c may lead to decreased angiotensin-converting enzyme-2 (ACE2) expression, which in turn may increase the potential of infection, inflammation, and the complications of coronavirus disease. Conclusion: miR-200c and its correlation with ACE2 can be used as early prognostic and diagnostic markers.
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Arora M, Sarda P, Thakker V, Waikhom P, Sharma R, Baisoya S, Rawat J, Azad R. Pneumomediastinum: Radiological profile and associations of uncommon complication of COVID-19. J Family Med Prim Care 2022; 11:537-541. [PMID: 35360790 PMCID: PMC8963614 DOI: 10.4103/jfmpc.jfmpc_1346_21] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/08/2021] [Accepted: 10/13/2021] [Indexed: 11/04/2022] Open
Abstract
Introduction: Materials and Methods: Results: Conclusion:
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Popova AY, Ezhlova EB, Melnikova AA, Smirnov VS, Lyalina LV, Ermakov AV, Solomashchenko NI, Kovalchuk IV, Vasilenko EA, Romanenko EN, Zvoliborskaya AV, Ryabykh AV, Dmitrienko LI, Mezhlumyan NA, Sharova AA, Vetrov VV, Totolian AA. Characteristic of herd immunity among the population of Stavropol region amid the COVID-19 epidemic. JOURNAL INFECTOLOGY 2021. [DOI: 10.22625/2072-6732-2021-13-4-79-89] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction. The first pandemic in the 21st century, caused by the pathogenic representative of the coronavirus SARS-CoV-2, began in the Chinese city of Wuhan, where the first outbreak of coronavirus pneumonia was recorded in December 2019. The disease spread so quickly around the world that already on February 11, 2020, WHO was forced to declare a pandemic of the “coronavirus disease 2019” COVID-19. The first case of COVID-19 in the Stavropol Territory was registered on March 20, 2020, and three weeks later, starting from the 15th week of the year, a steady increase in the incidence began, which lasted until the 52nd week. During the study period, the incidence increased from 21.1 to 28.3 per hundred thousand of the population. Growth 1.3 times.Purpose: to determine the dynamics of population immunity among the population of the Stavropol Territory in 2020-2021. during the period of an epidemic increase in the incidence of COVID-19. Materials and methods. The SARS-CoV-2 study was carried out according to a unified methodology within the framework of the program for assessing the population immunity of the population of the Russian Federation, developed by Rospotrebnadzor with the participation of the St. Pasteur. In total, 2688 people were examined, divided into 7 age groups. In the examined individuals, the level of specific IgG to the SARS-CoV-2 nucleocapsid was determined by the enzyme immunoassay.Results. The level of seroprevalence among residents of the Stavropol Territory was 9.8%. The largest proportion of seropositive individuals was found in the age groups 1-6 and 7-13 years old (19.2% and 19.7%, respectively). Seroprevalence had no gender differences and ranged from 9.3% to 10.8%. When assessing the distribution of the proportion of seropositive persons in different geographic territories of the region, it was found that the maximum proportion was found in the Kochubeevsky district (23.1%), the minimum in Kislovodsk (7.7%). Among convalescents, the content of specific antibodies to SARS-CoV-2 was noted in 73.3%, which is 7.8 times higher than the average population level. When conducting seromonitoring in the 2nd half of 2020, a 10-fold increase in seroprevalence was recorded, accompanied by a decrease in incidence from the 5th week of 2021. Among asymptomatic volunteers in whom SARS-CoV-2 RNA was detected by the polymerase chain reaction, antibody titers to viruses were found in 78.6%, which corresponds to the seroprevalence of convalescents. The proportion of seropositive persons among those who have come into contact with COVID-19 patients was 16.4%, (1.8 times higher than the average for the population). Out of 262 seroprevalent volunteers, the asymptomatic form of SARS-CoV-2 was detected in 92% of the examined, which indicates a significant role of the number of asymptomatic forms of infection in the epidemic process of COVID-19.Conclusion. The results of assessing the population immunity of the population of the Stavropol Territory indicate that it has not yet reached the threshold level at which a decrease in the intensity of the COVID-19 epidemic process can be expected.
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Affiliation(s)
- A. Yu. Popova
- Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing
| | - E. B. Ezhlova
- Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing
| | - A. A. Melnikova
- Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing
| | - V. S. Smirnov
- Saint-Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur
| | - L. V. Lyalina
- Saint-Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur
| | - A. V. Ermakov
- Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing, Department in the Stavropol Territory
| | | | - I. V. Kovalchuk
- Federal Service for Supervision of Consumer Rights Protection and Human Wellbeing, Department in the Stavropol Territory
| | - E. A. Vasilenko
- Center for Hygiene and Epidemiology in the Stavropol Territory
| | - E. N. Romanenko
- Center for Hygiene and Epidemiology in the Stavropol Territory
| | | | - A. V. Ryabykh
- Center for Hygiene and Epidemiology in the Stavropol Territory
| | | | | | - A. A. Sharova
- Saint-Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur
| | - V. V. Vetrov
- Saint-Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur
| | - A. A. Totolian
- Saint-Petersburg Research Institute of Epidemiology and Microbiology named after Pasteur
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Colagrossi L, Mattana G, Piccioni L, Cento V, Perno CF. Viral Respiratory Infections: New Tools for a Rapid Diagnosis. Semin Respir Crit Care Med 2021; 42:747-758. [PMID: 34918318 DOI: 10.1055/s-0041-1739306] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Respiratory tract infection is one of the most common diseases in human worldwide. Many viruses are implicated in these infections, including emerging viruses, such as the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Identification of the causative viral pathogens of respiratory tract infections is important to select a correct management of patients, choose an appropriate treatment, and avoid unnecessary antibiotics use. Different diagnostic approaches present variable performance in terms of accuracy, sensitivity, specificity, and time-to-result, that have to be acknowledged to be able to choose the right diagnostic test at the right time, in the right patient. This review describes currently available rapid diagnostic strategies and syndromic approaches for the detection of viruses commonly responsible for respiratory diseases.
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Affiliation(s)
- Luna Colagrossi
- Department of Laboratories, Bambino Gesù Children's Hospital, Rome, Italy
| | - Giordana Mattana
- Department of Laboratories, Bambino Gesù Children's Hospital, Rome, Italy
| | - Livia Piccioni
- Department of Laboratories, Bambino Gesù Children's Hospital, Rome, Italy
| | - Valeria Cento
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy
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Emadi-Baygi M, Ehsanifard M, Afrashtehpour N, Norouzi M, Joz-Abbasalian Z. Corona Virus Disease 2019 (COVID-19) as a System-Level Infectious Disease With Distinct Sex Disparities. Front Immunol 2021; 12:778913. [PMID: 34912345 PMCID: PMC8667725 DOI: 10.3389/fimmu.2021.778913] [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: 09/17/2021] [Accepted: 11/11/2021] [Indexed: 01/08/2023] Open
Abstract
The current global pandemic of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) causing COVID-19, has infected millions of people and continues to pose a threat to many more. Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the Renin-Angiotensin System (RAS) expressed on the surface of the lung, heart, kidney, neurons, and endothelial cells, which mediates SARS-CoV-2 entry into the host cells. The cytokine storms of COVID-19 arise from the large recruitment of immune cells because of the dis-synchronized hyperactive immune system, lead to many abnormalities including hyper-inflammation, endotheliopathy, and hypercoagulability that produce multi-organ dysfunction and increased the risk of arterial and venous thrombosis resulting in more severe illness and mortality. We discuss the aberrated interconnectedness and forthcoming crosstalks between immunity, the endothelium, and coagulation, as well as how sex disparities affect the severity and outcome of COVID-19 and harm men especially. Further, our conceptual framework may help to explain why persistent symptoms, such as reduced physical fitness and fatigue during long COVID, may be rooted in the clotting system.
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Affiliation(s)
- Modjtaba Emadi-Baygi
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Mahsa Ehsanifard
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Najmeh Afrashtehpour
- Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Shahrekord, Iran
| | - Mahnaz Norouzi
- Department of Research and Development, Erythrogen Medical Genetics Lab, Isfahan, Iran
| | - Zahra Joz-Abbasalian
- Clinical Laboratory, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Pedler RL, Speck PG. Marine mollusc extracts-Potential source of SARS-CoV-2 antivirals. Rev Med Virol 2021; 32:e2310. [PMID: 34726308 PMCID: PMC8646538 DOI: 10.1002/rmv.2310] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/10/2021] [Accepted: 10/11/2021] [Indexed: 12/28/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a novel human coronavirus and the causative agent of coronavirus disease 2019 (Covid‐19). There is an urgent need for effective antivirals to treat current Covid‐19 cases and protect those unable to be vaccinated against SARS‐CoV‐2. Marine molluscs live in an environment containing high virus densities (>107 virus particles per ml), and there are an estimated 100,000 species in the phylum Mollusca, demonstrating the success of their innate immune system. Mollusc‐derived antivirals are yet to be used clinically despite the activity of many extracts, including against human viruses, being demonstrated in vitro. Hemolymph of the Pacific oyster (Crassostrea gigas) has in vitro antiviral activity against herpes simplex virus and human adenovirus, while antiviral action against SARS‐CoV‐2 has been proposed by in silico studies. Such evidence suggests that molluscs, and in particular C. gigas hemolymph, may represent a source of antivirals for human coronaviruses.
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Affiliation(s)
- Rebecca L Pedler
- College of Science and Engineering, Flinders University, Bedford Park, South Australia, Australia
| | - Peter G Speck
- College of Science and Engineering, Flinders University, Bedford Park, South Australia, Australia
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Hashemian SM, Shafigh N, Afzal G, Jamaati H, Tabarsi P, Marjani M, Malekmohammad M, Mortazavi SM, Khoundabi B, Mansouri D, Moniri A, Hajifathali A, Roshandel E, Mortaz E, Adcock IM. Plasmapheresis reduces cytokine and immune cell levels in COVID-19 patients with acute respiratory distress syndrome (ARDS). Pulmonology 2021; 27:486-492. [PMID: 33358260 PMCID: PMC7834188 DOI: 10.1016/j.pulmoe.2020.10.017] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND In December 2019, pneumonia associated with a novel coronavirus (COVID-19) was reported in Wuhan, China. Acute respiratory distress syndrome (ARDS) is the most frequently observed complication in COVID-19 patients with high mortality rates. OBJECTIVE OF STUDY To observe the clinical effect of plasmapheresis on excessive inflammatory reaction and immune features in patients with severe COVID-19 at risk of ARDS. MATERIALS AND METHODS In this single-center study, we included 15 confirmed cases of COVID-19 at Masih Daneshvari Hospital, in March 2020 in Tehran, Iran. COVID-19 cases were confirmed by RT-PCR and CT imaging according to WHO guidelines. Plasmapheresis was performed to alleviate cytokine-induced ARDS. The improvement in oxygen delivery (PaO2/FiO2), total number of T cells, liver enzymes, acute reaction proteins, TNF-α and IL-6 levels were evaluated. RESULTS Inflammatory cytokine levels (TNF-α, IL-6), and acute phase reaction proteins including ferritin and CRP were high before plasmapheresis. After plasmapheresis, the levels of PaO2/FiO2, acute phase reactants, inflammatory mediators, liver enzymes and bilirubin were significantly reduced within a week (p < 0.05). In contrast, although the number of T helper cells decreased immediately after plasmapheresis, they rose to above baseline levels after 1 week. Nine out of fifteen patients on non-invasive positive-pressure ventilation (NIPPV) survived whilst the six patients undergoing invasive mechanical ventilation (IMV) died. CONCLUSION Our data suggests that plasmapheresis improves systemic cytokine and immune responses in patients with severe COVID-19 who do not undergo IMV. Further controlled studies are required to explore the efficacy of plasmapheresis treatment in patients with COVID-19.
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Affiliation(s)
- Seyed MohammadReza Hashemian
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Navid Shafigh
- Department of Anesthesiology and Critical Care Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golnaz Afzal
- Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Jamaati
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Marjani
- Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Malekmohammad
- Tracheal Diseases Research Center (TDRC), NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Batoul Khoundabi
- Research Center For Health Management in Mass Gathering, Red Crescent Society of the Islamic Republic of Iran, Tehran, Iran
| | - Davood Mansouri
- Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afshin Moniri
- Virology Research Center (VRC), NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Hajifathali
- Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elham Roshandel
- Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Esmaeil Mortaz
- Clinical Tuberculosis and Epidemiology Research Center, NRITLD, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ian M Adcock
- Cell and Molecular Biology Group, Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK; Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
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Chen T, Lin YX, Zha Y, Sun Y, Tian J, Yang Z, Lin SW, Yu F, Chen ZS, Kuang BH, Lei JJ, Nie YJ, Xu Y, Tian DB, Li YZ, Yang B, Xu Q, Yang L, Zhong N, Zheng M, Li Y, Zhao J, Zhang XY, Feng L. A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19. mBio 2021; 12:e0137221. [PMID: 34634929 PMCID: PMC8510538 DOI: 10.1128/mbio.01372-21] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 09/13/2021] [Indexed: 12/25/2022] Open
Abstract
Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.
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Affiliation(s)
- Tao Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yu-Xin Lin
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yan Zha
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Ying Sun
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jinxiu Tian
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhiying Yang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shan-Wen Lin
- Yangjiang Key Laboratory of Respiratory Disease, Department of Respiratory Medicine, People’s Hospital of Yangjiang, Yangjiang, Guangdong, China
| | - Fuxun Yu
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Zi-Sheng Chen
- Department of Respiratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
| | - Bo-Hua Kuang
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jin-Ju Lei
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ying-jie Nie
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Yonghao Xu
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Dong-Bo Tian
- Department of Respiratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, China
| | - Ying-Zi Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Bin Yang
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Qiang Xu
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Li Yang
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Nanshan Zhong
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Meizhen Zheng
- Department of Biology, Southern University of Science and Technology, Shenzhen, China
| | - Yimin Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jincun Zhao
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiang-Yan Zhang
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People’s Hospital, Guizhou University, Guizhou, China
| | - Lin Feng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China
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Gavriilaki E, Eftychidis I, Papassotiriou I. Update on endothelial dysfunction in COVID-19: severe disease, long COVID-19 and pediatric characteristics. J LAB MED 2021. [DOI: 10.1515/labmed-2021-0134] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Abstract
Objectives
To review current literature on the role of endothelial dysfunction in coronavirus disease-2019 (COVID-19) infection in terms of pathophysiology, laboratory features and markers, clinical phenotype in adults and children, as well as long COVID-19.
Content
We conducted a thorough assessment of the literature and critically analyzed current data, mostly utilizing the PubMed and Medline search engines to find original studies published in the previous decade.
Summary and Outlook
Accumulating evidence suggests that endothelial dysfunction may be a common denominator of severe COVID-19 in adults and children, as well as long COVID-19, implicating mutual pathophysiological pathways. This narrative review summarizes the up-to-date knowledge of endothelial dysfunction caused by COVID-19, including novel aspects of long COVID-19 and pediatric disease. This knowledge is important in order not only to understand the multisystemic attack of COVID-19, but also to improve patient management and prognosis.
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Affiliation(s)
- Eleni Gavriilaki
- Hematology Department – BMT Unit , G. Papanikolaou Hospital , Thessaloniki , Greece
| | - Ioannis Eftychidis
- Hematology Department – BMT Unit , G. Papanikolaou Hospital , Thessaloniki , Greece
| | - Ioannis Papassotiriou
- Department of Clinical Biochemistry , “Aghia Sophia” Children’s Hospital , Athens , Greece
- IFCC Emerging Technologies Division , Emerging Technologies in Pediatric Laboratory Medicine (C-ETPLM) , Milan , Italy
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