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Khan HR, Sultan R, Javeed M, Yasmeen H, Arooj I, Janiad S. Functional foods and immune system: A sustainable inhibitory approach against SARS-COV-2. Antivir Ther 2025; 30:13596535251322297. [PMID: 40138520 DOI: 10.1177/13596535251322297] [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: 03/29/2025]
Abstract
Background: COVID-19 has become the center of attention since its outbreak in December 2019. Despite the discovery of its preventive vaccine, role of healthy immune system is undebatable. Functional foods are continuously hunted as a promising option for a safe natural therapeutic treatment.Purpose: This review demonstrates how functional foods can boost host immune system, promote antiviral operation, and synthesize biologically effective molecules against SARS-COV-2.Research Methodology: For current review, online search was conducted for nature-based functional immune boosters against SARS-COV-2.Conclusion: Functional foods, alongside a healthy lifestyle, fortifies the human immune system and could all help to dramatically lower the cost burden of COVID-19, the suffering of the patients, and the mortality rates worldwide.
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Affiliation(s)
- Hubza Ruatt Khan
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
| | - Rabia Sultan
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
| | - Mehvish Javeed
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
| | - Humaira Yasmeen
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
| | - Iqra Arooj
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
| | - Sara Janiad
- Department of Microbiology and Molecular Genetics, The Women University Multan, Multan, Pakistan
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Aksoyalp ZŞ, Erdoğan BR, Aksun S, Sözmen MK, Aksun M, Buharalıoğlu CK, Altıncı-Karahan N, Turgut NH, Kaya-Temiz T. Trimethylamine N-oxide as a potential prognostic biomarker for mortality in patients with COVID-19 disease. Adv Med Sci 2025; 70:174-183. [PMID: 39920994 DOI: 10.1016/j.advms.2025.02.002] [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: 07/12/2024] [Revised: 09/30/2024] [Accepted: 02/04/2025] [Indexed: 02/10/2025]
Abstract
PURPOSE Trimethylamine N-oxide (TMAO) is suggested as a biomarker for inflammatory and cardiovascular diseases which are identified as risk factors for severe cases of coronavirus disease 2019 (COVID-19). Our primary aim was to assess prognostic potential of serum TMAO levels in predicting COVID-19-related mortality. The secondary aim was to examine the potential of various biochemical parameters, particularly those associated with inflammation or thrombosis, as predictors of mortality. PATIENTS AND METHODS In this prospective and single-centre study, COVID-19 patients were categorized as death (group 1) or discharged (group 2) based on their in-hospital mortality status. The characteristics of participants were documented, and clinical data, including TMAO, angiotensin-converting enzyme-2 (ACE2), and neutrophil to lymphocyte ratio (NLR), were determined. The association of these independent variables with the COVID-19-related mortality, was assessed by calculation of crude odds ratios (OR) in bivariate and logistic regression analysis. Receiver operation characteristic (ROC) analysis was used for cut-off values. RESULTS The serum levels of TMAO, ACE2 and NLR were markedly higher in group 1 on the days of hospital admission (p < 0.05, p < 0.05, and p < 0.01, respectively). Serum TMAO levels (OR 1.422; 95 % CI [1.067-1.894]; p = 0.016) and NLR (OR 1.166; 95 % CI [1.012-1.343]; p = 0.033) were determined as independent predictors for COVID-19-related mortality with after multivariate logistic regression analysis. The optimal cut-off values were detected as 7.9 ng/ml for TMAO (71 % sensitivity, 68 % specificity, AUC = 0.701). CONCLUSIONS The findings of this initial study indicate that serum TMAO levels and NLR may be useful in predicting mortality in the early stages of COVID-19.
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Affiliation(s)
| | - Betül Rabia Erdoğan
- Department of Pharmacology, Izmir Katip Celebi University, Izmir, Turkey; Turkish Medicines and Medical Devices Agency, Ankara, Turkey
| | - Saliha Aksun
- Department of Medical Biochemistry, Izmir Katip Celebi University, Izmir, Turkey
| | - Melih Kaan Sözmen
- Department of Public Health, Izmir Katip Celebi University, Izmir, Turkey; Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, USA
| | - Murat Aksun
- Department of Anesthesiology and Reanimation, Izmir Katip Celebi University, Izmir, Turkey
| | | | - Nagihan Altıncı-Karahan
- Department of Anesthesiology and Reanimation, Izmir Atatürk Training and Research Hospital, Izmir, Turkey
| | | | - Tijen Kaya-Temiz
- Department of Medical Pharmacology, Izmir Katip Celebi University, Izmir, Turkey
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Tanwar S, Mishra N, Sharma P, Kaur A. Increased serum ferritin is associated with severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis: A quantitative analysis. Indian J Ophthalmol 2025; 73:223-227. [PMID: 38990622 PMCID: PMC11991563 DOI: 10.4103/ijo.ijo_574_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 11/07/2023] [Accepted: 04/17/2024] [Indexed: 07/12/2024] Open
Abstract
CONTEXT Effect of serum ferritin on severity of coronavirus disease 2019 (COVID-19)-associated rhino-orbito-cerebral mucormycosis. PURPOSE To study the association between increased serum ferritin and severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis. SETTINGS AND DESIGN A cross-sectional study. METHODS Hundred ( n ) out of 155 treatment-naive patients of COVID-19 infection presenting with the signs and symptoms of rhino-orbito-cerebral mucormycosis were enrolled in study. Based on the classification proposed by Honavar, the study patients were classified into four stages: Stage 1: involvement of the nasal mucosa ( n = 11), Stage 2: involvement of paranasal sinuses ( n = 14), Stage 3: involvement of the orbit ( n = 37), Stage 4: involvement of the central nervous system ( n = 38). Stage 3 was further divided into four substages: 3a: nasolacrimal duct, medial orbit, vision unaffected ( n = 4); 3b: diffuse orbital involvement (>1 quadrant or >2 structures), vision unaffected ( n = 15); 3c: central retinal artery occlusion or ophthalmic artery occlusion, superior ophthalmic vein thrombosis, involvement of superior orbital fissure, inferior orbital fissure, orbital apex, diminution or loss of vision ( n = 13); 3d: bilateral orbital involvement ( n = 5). Fasting blood sugar (FBS), postprandial blood sugar (PPBS), and inflammatory markers (serum ferritin, interleukin-6, C-reactive protein, and D-dimer) were assessed. Serum level of ferritin was analyzed by using chemiluminescence immunoassay method. RESULTS Mean FBS (mg/dl) was 165.03 ± 70.43 for stage 1, 185.67 ± 64.82 for stage 2, 159.05 ± 68.60 for stage 3, and 158.20 ± 62.05 for stage 4. Mean PPBS (mg/dl) was 238.70 ± 141.29 for stage 1, 252 ± 103.69 for stage 2, 257.09 ± 103.48 for stage 3, and 229.53 ± 76.81 for stage 4. Mean serum ferritin (μg/l) was 302.67 ± 266.95 in stage 1, 444.19 ± 116.36 in stage 2, 504.85 ± 205.99 in stage 3, and 825.95 ± 777.30 in stage 4. A statistically significant increase in serum ferritin levels with severity of disease ( P = 0.005) was noted. Similar trend was observed in substages of stage 3. Pearson correlation analysis showed a positive correlation between serum ferritin and severity of disease ( P = 0.0007). CONCLUSION Increased serum ferritin was significantly independently associated with severity of orbital disease in COVID-19-associated rhino-orbito-cerebral mucormycosis.
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Affiliation(s)
- Shashi Tanwar
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Nibha Mishra
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Prachi Sharma
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Apjit Kaur
- Department of Ophthalmology, King George Medical University, Lucknow, Uttar Pradesh, India
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Borges R, Bandeira CCS, Zerbinati RM, Palmieri M, Schwab G, Henrique Braz-Silva P, A L Lindoso J, Martinho H. Infrared spectroscopy as a predictive tool for the severity of COVID-19 using patient's saliva: A strategy to avoid hyperinflammation. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 317:124320. [PMID: 38718743 DOI: 10.1016/j.saa.2024.124320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 03/01/2024] [Accepted: 04/19/2024] [Indexed: 05/31/2024]
Abstract
Discriminate the severity level of COVID-19 disease is still a challenge. Here we investigate the capability of micro-infrared absorption spectroscopy (micro-FTIR) to probe COVID-19 severity level and predict hyperinflammation, correlating the assigned vibrational data to relevant biomolecules related to the immune system. Saliva of 184 patients was analysed by ELISA assay (Hepcidin) and micro-FTIR. Vibrational bands related to IgM and IgA can discriminate healthy from Severe individuals (sensitivity ≥ 0.749, specificity ≥ 0.945) and are less effective in discriminating Mild or Moderate individuals from the Severe group (sensitivity ≥ 0.628, specificity ≥ 0.867). Analysis of the second derivative of spectra probed increased levels of IL-6 in the saliva a key additional information for the degree of severity prediction. Because the model discriminates all the groups regarding the Severe group, it predicts an intense state of inflammation based on FTIR analysis. It is a powerful tool for predicting hyperinflammation conditions related to SARS-CoV-2 infection and may be an ally in implementing drugs or therapeutic approaches to manage COVID-19 in the Severe stage in healthcare facilities.
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Affiliation(s)
- Roger Borges
- Center for Natural and Human Sciences, Federal University of ABC (UFABC), Brazil; School of Biomedical Engineering, Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, Brazil
| | - Carla C S Bandeira
- Center for Natural and Human Sciences, Federal University of ABC (UFABC), Brazil
| | - Rodrigo M Zerbinati
- Institute of Infectious Diseases Emílio Ribas, Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Michelle Palmieri
- Department of Stomatology, University of São Paulo School of Dentistry, Brazil
| | - Gabriela Schwab
- Institute of Infectious Diseases Emílio Ribas, Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Paulo Henrique Braz-Silva
- Institute of Infectious Diseases Emílio Ribas, Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil; Department of Stomatology, University of São Paulo School of Dentistry, Brazil
| | - José A L Lindoso
- Institute of Infectious Diseases Emílio Ribas, Institute of Tropical Medicine of São Paulo, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Herculano Martinho
- Center for Natural and Human Sciences, Federal University of ABC (UFABC), Brazil.
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Osyodlo GV, Husieva SA, Svicharova SV, Savichan KV. Autoimmune Hemolytic Anemia Associated with COVID-19 Infection in a Patient with High Cardio-metabolic Risk. Mil Med 2024; 189:e2274-e2279. [PMID: 38015753 DOI: 10.1093/milmed/usad446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 10/19/2023] [Accepted: 11/01/2023] [Indexed: 11/30/2023] Open
Abstract
The article analyses data on the occurrence of hematological abnormalities in severe acute respiratory syndrome 2 infection. Among these hematological abnormalities, the majority of patients develop a hypercoagulable state associated with thromboembolic complications and poor prognosis. Approximately one-third of patients with severe acute respiratory syndrome 2 infection are diagnosed with mild to severe thrombocytopenia. Another hematological autoimmune disease observed in patients with coronavirus disease 2019 is autoimmune hemolytic anemia. A clinical case with the development of autoimmune hemolytic anemia in the setting of coronavirus infection was described. The diagnosis was based on the presence of anemia, reticulocytosis, a significant decrease in haptoglobin levels, and a positive antiglobulin test (Coombs test). Given the comorbidity, the risks of adverse effects of severe coronavirus disease were high, despite this, it was possible to achieve clinical and hematological remission of autoimmune hemolytic anemia by prescribing pathogenetic therapy with anti-CD-20 monoclonal antibody (rituximab), recombinant erythropoietin and glucocorticoid hormones. This clinical case demonstrates the possibility of successful treatment of patients with severe hemolytic anemia. Special attention should be paid to the discrepancy between the severity of the condition and objective data. This case demonstrates the need for a more in-depth approach to each patient with anemia associated with coronavirus disease infection, namely, in the presence of anemic syndrome, it is imperative to include a full range of laboratory tests.
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Affiliation(s)
- Galyna V Osyodlo
- Military Therapy Department, Ukrainian Military Medical Academy, Kyiv 01010, Ukraine
| | - Svitlana A Husieva
- Military Therapy Department, Ukrainian Military Medical Academy, Kyiv 01010, Ukraine
| | - Svitlana V Svicharova
- Military Therapy Department, Ukrainian Military Medical Academy, Kyiv 01010, Ukraine
| | - Kyrylo V Savichan
- Military Therapy Department, Ukrainian Military Medical Academy, Kyiv 01010, Ukraine
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Koulenti D, Paramythiotou E, Almyroudi MP, Karvouniaris M, Markou N, Paranos P, Routsi C, Meletiadis J, Blot S. Severe mold fungal infections in critically ill patients with COVID-19. Future Microbiol 2024; 19:825-840. [PMID: 38700287 PMCID: PMC11290760 DOI: 10.2217/fmb-2023-0261] [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: 11/21/2023] [Accepted: 02/20/2024] [Indexed: 05/05/2024] Open
Abstract
The SARS-CoV-2 pandemic put an unprecedented strain on modern societies and healthcare systems. A significantly higher incidence of invasive fungal co-infections was noted compared with the pre-COVID-19 era, adding new diagnostic and therapeutic challenges in the critical care setting. In the current narrative review, we focus on invasive mold infections caused by Aspergillus and Mucor species in critically ill COVID-19 patients. We discuss up-to-date information on the incidence, pathogenesis, diagnosis and treatment of these mold-COVID-19 co-infections, as well as recommendations on preventive and prophylactic interventions. Traditional risk factors were often not recognized in COVID-19-associated aspergillosis and mucormycosis, highlighting the role of other determinant risk factors. The associated patient outcomes were worse compared with COVID-19 patients without mold co-infection.
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Affiliation(s)
- Despoina Koulenti
- Department of Critical Care Medicine, King's College Hospital NHS Foundation Trust, London, UK
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
| | | | - Maria Panagiota Almyroudi
- Emergency Department, Attikon University Hospital, National & Kapodistrian University of Athens, Greece
| | | | - Nikolaos Markou
- Intensive Care Unit of Latseio Burns Centre, Thriasio General Hospital of Elefsina, Greece
| | - Paschalis Paranos
- Clinical Microbiology Laboratory, Attikon University Hospital, National & Kapodistrian Uni-versity of Athens, Greece
| | - Christina Routsi
- First Department of Intensive Care, School of Medicine, National & Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece
| | - Joseph Meletiadis
- Clinical Microbiology Laboratory, Attikon University Hospital, National & Kapodistrian Uni-versity of Athens, Greece
| | - Stijn Blot
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia
- Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium
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Eckstein J, Skeries V, Pöhler G, Babazade N, Kaireit T, Gutberlet M, Kornemann N, Hellms S, Pfeil A, Bucher AM, Hansmann G, Beerbaum P, Hansen G, Wacker F, Vogel-Claussen J, Wetzke M, Renz DM. Multiparametric Cardiovascular MRI Assessment of Post-COVID Syndrome in Children in Comparison to Matched Healthy Individuals. Invest Radiol 2024; 59:472-478. [PMID: 38117123 DOI: 10.1097/rli.0000000000001048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2023]
Abstract
BACKGROUND Post-COVID syndrome (PCS) can adversely affect the quality of life of patients and their families. In particular, the degree of cardiac impairment in children with PCS is unknown. OBJECTIVE The aim of this study was to identify potential cardiac inflammatory sequelae in children with PCS compared with healthy controls. METHODS This single-center, prospective, intraindividual, observational study assesses cardiac function, global and segment-based strains, and tissue characterization in 29 age- and sex-matched children with PCS and healthy children using a 3 T magnetic resonance imaging (MRI). RESULTS Cardiac MRI was carried out over 36.4 ± 24.9 weeks post-COVID infection. The study cohort has an average age of 14.0 ± 2.8 years, for which the majority of individuals experience from fatigue, concentration disorders, dyspnea, dizziness, and muscle ache. Children with PSC in contrast to the control group exhibited elevated heart rate (83.7 ± 18.1 beats per minute vs 75.2 ± 11.2 beats per minute, P = 0.019), increased indexed right ventricular end-diastolic volume (95.2 ± 19.2 mlm -2 vs 82.0 ± 21.5 mlm -2 , P = 0.018) and end-systolic volume (40.3 ± 7.9 mlm -2 vs 34.8 ± 6.2 mlm -2 , P = 0.005), and elevated basal and midventricular T1 and T2 relaxation times ( P < 0.001 to P = 0.013). Based on the updated Lake Louise Criteria, myocardial inflammation is present in 20 (69%) children with PCS. No statistically significant difference was observed for global strains. CONCLUSIONS Cardiac MRI revealed altered right ventricular volumetrics and elevated T1 and T2 mapping values in children with PCS, suggestive for a diffuse myocardial inflammation, which may be useful for the diagnostic workup of PCS in children.
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Affiliation(s)
- Jan Eckstein
- From the Institute of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany (J.E., G.P., N.B., T.K., M.G., N.K., S.H., F.W., J.V.-C., D.M.R.); Clinic for Pediatric Pneumology, Allergology, and Neonatology, Hannover Medical School, Hannover, Germany (V.S., G.H., M.W.); Department of Internal Medicine III, University Hospital Jena, Jena, Germany (A.P.); Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Frankfurt am Main, Germany (A.M.B.); and Clinic for Pediatric Cardiology and Intensive Care, Hannover Medical School, Hannover, Germany (G.H., P.B.)
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Pereira TA, Espósito BP. Can iron chelators ameliorate viral infections? Biometals 2024; 37:289-304. [PMID: 38019378 DOI: 10.1007/s10534-023-00558-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 10/25/2023] [Indexed: 11/30/2023]
Abstract
The redox reactivity of iron is a double-edged sword for cell functions, being either essential or harmful depending on metal concentration and location. Deregulation of iron homeostasis is associated with several clinical conditions, including viral infections. Clinical studies as well as in silico, in vitro and in vivo models show direct effects of several viruses on iron levels. There is support for the strategy of iron chelation as an alternative therapy to inhibit infection and/or viral replication, on the rationale that iron is required for the synthesis of some viral proteins and genes. In addition, abnormal iron levels can affect signaling immune response. However, other studies report different effects of viral infections on iron homeostasis, depending on the class and genotype of the virus, therefore making it difficult to predict whether iron chelation would have any benefit. This review brings general aspects of the relationship between iron homeostasis and the nonspecific immune response to viral infections, along with its relevance to the progress or inhibition of the inflammatory process, in order to elucidate situations in which the use of iron chelators could be efficient as antivirals.
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Velasco JC, Vargas LJ, García L, Torres IJ, González IC. Oral mucormycosis associated with COVID-19 and diabetes mellitus: Case report and literature review. BIOMEDICA : REVISTA DEL INSTITUTO NACIONAL DE SALUD 2024; 44:10-15. [PMID: 38648346 PMCID: PMC11186624 DOI: 10.7705/biomedica.6970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 01/04/2024] [Indexed: 04/25/2024]
Abstract
Mucormycosis is an invasive opportunistic fungal infection with high mortality, mainly detected in people with COVID-19, especially those with underlying diseases such as diabetes mellitus. Mucormycosis prevalence is 0.005 to 1.7 cases per million inhabitants, and it has been increasing in countries like India and Pakistan. This mycosis can affect different organs, and clinical manifestations reflect the transmission mechanism. Frequent forms are rhino-orbital-cerebral and pulmonary. This disease should be suspected in patients with necrotic injuries on mucous membranes or skin. We present a case of a patient with diabetes mellitus and diagnosed with oral mucormycosis associated with COVID-19.
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Affiliation(s)
- Julio César Velasco
- Departamento de Investigación, Hospital Regional de la Orinoquía, Yopal, ColombiaHospital Regional de la OrinoquíaDepartamento de InvestigaciónHospital Regional de la OrinoquíaYopalColombia
| | - Ledmar Jovanny Vargas
- Departamento de Investigación, Hospital Regional de la Orinoquía, Yopal, ColombiaHospital Regional de la OrinoquíaDepartamento de InvestigaciónHospital Regional de la OrinoquíaYopalColombia
| | - Lorena García
- Departamento de Investigación, Hospital Regional de la Orinoquía, Yopal, ColombiaHospital Regional de la OrinoquíaDepartamento de InvestigaciónHospital Regional de la OrinoquíaYopalColombia
| | - Iván José Torres
- Cirugía Maxilofacial, Hospital Regional de la Orinoquía, Yopal, ColombiaHospital Regional de la OrinoquíaHospital Regional de la OrinoquíaYopalColombia
| | - Iván Camilo González
- Medicina de Urgencias, Hospital Regional de la Orinoquía, Yopal, ColombiaHospital Regional de la OrinoquíaHospital Regional de la OrinoquíaYopalColombia
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Athanassiou L, Kostoglou-Athanassiou I, Nikolakopoulou S, Konstantinou A, Mascha O, Siarkos E, Samaras C, Athanassiou P, Shoenfeld Y. Vitamin D Levels as a Marker of Severe SARS-CoV-2 Infection. Life (Basel) 2024; 14:210. [PMID: 38398719 PMCID: PMC10890332 DOI: 10.3390/life14020210] [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: 12/22/2023] [Revised: 01/21/2024] [Accepted: 01/30/2024] [Indexed: 02/25/2024] Open
Abstract
The SARS-CoV-2 virus may cause severe infection, which is associated with diverse clinical manifestations. Vitamin D has immunomodulating properties and may enhance the body's defense system against invading pathogenic organisms. The aim was to assess 25(OH)D3 levels in patients hospitalized for severe infection from the SARS-CoV-2 virus and explore the relationship between 25(OH)D3 and outcomes. In a group of 88 patients hospitalized for severe infection from the SARS-CoV-2 virus and a control group matched for age and sex, the levels of 25(OH)D3 were analyzed. Levels of 25(OH)D3 were 17.36 ± 8.80 ng/mL (mean ± SD) compared with 24.34 ± 10.34 ng/mL in patients with severe SARS-CoV-2 infection and the control group, respectively, p < 0.001 (Student's t-test). 25(OH)D3 levels were significantly related to outcomes, i.e., survival as opposed to non-survival, as more patients with 25(OH)D3 deficiency (0-10 ng/mL) and insufficiency (10-20 ng/mL) had a fatal outcome as compared with those with vitamin D sufficiency (p < 0.001, chi-square test, p < 0.001, Fisher's exact test). Levels of 25(OH)D3 were inversely related to C-reactive protein (CRP), ferritin, d-dimer, and fibrinogen levels (p < 0.001, linear regression analysis, beta coefficient of variation, -0.176, -0.160, -0.178, and -0.158, respectively). Vitamin D deficiency observed in severe SARS-CoV-2 infection was related to disease outcomes.
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Affiliation(s)
- Lambros Athanassiou
- COVID-19 Department, Asclepeion Hospital, Voula, GR16673 Athens, Greece; (L.A.); (S.N.); (A.K.); (E.S.); (C.S.)
| | | | - Sofia Nikolakopoulou
- COVID-19 Department, Asclepeion Hospital, Voula, GR16673 Athens, Greece; (L.A.); (S.N.); (A.K.); (E.S.); (C.S.)
| | - Alexandra Konstantinou
- COVID-19 Department, Asclepeion Hospital, Voula, GR16673 Athens, Greece; (L.A.); (S.N.); (A.K.); (E.S.); (C.S.)
| | - Olga Mascha
- Department of Biochemistry, Asclepeion Hospital, Voula, GR16673 Athens, Greece;
| | - Evangelos Siarkos
- COVID-19 Department, Asclepeion Hospital, Voula, GR16673 Athens, Greece; (L.A.); (S.N.); (A.K.); (E.S.); (C.S.)
| | - Charilaos Samaras
- COVID-19 Department, Asclepeion Hospital, Voula, GR16673 Athens, Greece; (L.A.); (S.N.); (A.K.); (E.S.); (C.S.)
| | | | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Reichman University, Herzelya 4610101, Israel;
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Datarkar A, Bhawalkar A, Shah V, Manekar V, Gadve V, Daware S, Walkey D, Gioia F, Acero J. Osteomyelitis of the Jaw Due to Mucormycosis after Coronavirus Disease 2019 Infection - A Prospective Study. Ann Maxillofac Surg 2024; 14:40-45. [PMID: 39184403 PMCID: PMC11340825 DOI: 10.4103/ams.ams_16_24] [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: 02/06/2024] [Revised: 05/09/2024] [Accepted: 05/23/2024] [Indexed: 08/27/2024] Open
Abstract
Introduction The objective of the study was to describe the incidence, clinical characteristics, treatment and outcome of patients with rhinocerebral coronavirus disease 2019-associated mucormycosis (CAM). Materials and Methods We performed an unicentric observational study. A total of 113 cases of CAM were evaluated from January 2021 to June 2021. We described the overall incidence of CAM in Nagpur district up to June 2021, the clinical presentation of CAM, the subtype of CAM, the laboratory diagnosis, the type of surgical management in CAM, the pre-operative and 3-month post-operative C-reactive protein marker values, the post-operative healing and complications and the mortality rate. Results The mean age of the patients was 38.8 years. Rhinomaxillary subtype was the most common. All patients underwent medical as well as surgical intervention as the treatment modality. There was mortality in two patients. Discussion Study highlights the need for physicians to closely monitor coronavirus disease 2019 (COVID-19) patients, especially severe cases with pre-existing diabetes/receiving corticosteroid therapy and the need for patient education as early diagnosis and prompt treatment leads to better prognosis.
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Affiliation(s)
- Abhay Datarkar
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Amit Bhawalkar
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Vartik Shah
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Varsha Manekar
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Vandana Gadve
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Surendra Daware
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Damyanti Walkey
- Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Government Medical College Premises, Nagpur, Maharashtra, India
| | - Francesca Gioia
- Department of Infectious Disease, University Hospital Ramon y Cajal, IRYCIS and CIBER, Madrid, Spain
| | - Julio Acero
- Department of Oral and Maxillofacial Surgery, Ramón y Cajal and Puerta de Hierro University Hospitals, University of Alcala, IRYCIS, Madrid, Spain
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12
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Harte JV, Coleman-Vaughan C, Crowley MP, Mykytiv V. It's in the blood: a review of the hematological system in SARS-CoV-2-associated COVID-19. Crit Rev Clin Lab Sci 2023; 60:595-624. [PMID: 37439130 DOI: 10.1080/10408363.2023.2232010] [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: 04/10/2023] [Accepted: 06/27/2023] [Indexed: 07/14/2023]
Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented global healthcare crisis. While SARS-CoV-2-associated COVID-19 affects primarily the respiratory system, patients with COVID-19 frequently develop extrapulmonary manifestations. Notably, changes in the hematological system, including lymphocytopenia, neutrophilia and significant abnormalities of hemostatic markers, were observed early in the pandemic. Hematological manifestations have since been recognized as important parameters in the pathophysiology of SARS-CoV-2 and in the management of patients with COVID-19. In this narrative review, we summarize the state-of-the-art regarding the hematological and hemostatic abnormalities observed in patients with SARS-CoV-2-associated COVID-19, as well as the current understanding of the hematological system in the pathophysiology of acute and chronic SARS-CoV-2-associated COVID-19.
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Affiliation(s)
- James V Harte
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
- School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland
| | | | - Maeve P Crowley
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
- Irish Network for Venous Thromboembolism Research (INViTE), Ireland
| | - Vitaliy Mykytiv
- Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland
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13
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Wang Y, Shen M, Li Y, Shao J, Zhang F, Guo M, Zhang Z, Zheng S. COVID-19-associated liver injury: Adding fuel to the flame. Cell Biochem Funct 2023; 41:1076-1092. [PMID: 37947373 DOI: 10.1002/cbf.3883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/19/2023] [Accepted: 10/21/2023] [Indexed: 11/12/2023]
Abstract
COVID-19 is mainly characterized by respiratory disorders and progresses to multiple organ involvement in severe cases. With expansion of COVID-19 and SARS-CoV-2 research, correlative liver injury has been revealed. It is speculated that COVID-19 patients exhibited abnormal liver function, as previously observed in the SARS and MERS pandemics. Furthermore, patients with underlying diseases such as chronic liver disease are more susceptible to SARS-CoV-2 and indicate a poor prognosis accompanied by respiratory symptoms, systemic inflammation, or metabolic diseases. Therefore, COVID-19 has the potential to impair liver function, while individuals with preexisting liver disease suffer from much worse infected conditions. COVID-19 related liver injury may be owing to direct cytopathic effect, immune dysfunction, gut-liver axis interaction, and inappropriate medication use. However, discussions on these issues are infancy. Expanding research have revealed that angiotensin converting enzyme 2 (ACE2) expression mediated the combination of virus and target cells, iron metabolism participated in the virus life cycle and the fate of target cells, and amino acid metabolism regulated immune response in the host cells, which are all closely related to liver health. Further exploration holds great significance in elucidating the pathogenesis, facilitating drug development, and advancing clinical treatment of COVID-19-related liver injury. This article provides a review of the clinical and laboratory hepatic characteristics in COVID-19 patients, describes the etiology and impact of liver injury, and discusses potential pathophysiological mechanisms.
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Affiliation(s)
- Yingqian Wang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Min Shen
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
| | - Yujia Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangjuan Shao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Feng Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mei Guo
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zili Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shizhong Zheng
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Key Laboratory of Therapeutic Material of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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14
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Li Y, Cheng ZX, Luo T, Lyu HB. Therapeutic potential of iron chelators in retinal vascular diseases. Int J Ophthalmol 2023; 16:1899-1910. [PMID: 38028518 PMCID: PMC10626364 DOI: 10.18240/ijo.2023.11.24] [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: 04/27/2023] [Accepted: 08/24/2023] [Indexed: 12/01/2023] Open
Abstract
Iron is one of the necessary metal elements in the human body. There are numerous factors that control the balance of iron metabolism, and its storage and transportation mechanisms are intricate. As one of the most energy-intensive tissues in the body, the retina is susceptible to iron imbalance. The occurrence of iron overload in the retina leads to the generation of a significant quantity of reactive oxygen species. This will aggravate local oxidative stress and inflammatory reactions and even lead to ferroptosis, eventually resulting in retinal dysfunction. The blood-retina-retinal barrier is eventually harmed by oxidative stress and elevated inflammation, which are characteristics of retinal vascular disorders. The pathophysiology of retinal vascular disorders may be significantly influenced by iron. Recently, iron-chelating agents have been found to have antioxidative and anti-inflammatory actions in addition to iron chelating. Therefore, iron neutralization is considered to be a new and potentially useful therapeutic strategy. This article reviews the iron overload in retinal vascular diseases and discusses the therapeutic potential of iron-chelating agents.
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Affiliation(s)
- Yan Li
- Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
- Department of Ophthalmology, the People's Hospital of Jianyang, Chengdu 641400, Sichuan Province, China
| | - Zi-Xuan Cheng
- Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Ting Luo
- Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
- Department of Ophthalmology, the People's Hospital of Jianyang, Chengdu 641400, Sichuan Province, China
| | - Hong-Bin Lyu
- Department of Ophthalmology, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
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15
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Chaubey GK, Dilawari R, Modanwal R, Talukdar S, Dhiman A, Raje CI, Raje M. Excess iron aggravates the severity of COVID-19 infection. Free Radic Biol Med 2023; 208:186-193. [PMID: 37553026 DOI: 10.1016/j.freeradbiomed.2023.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/03/2023] [Accepted: 08/04/2023] [Indexed: 08/10/2023]
Abstract
Coronavirus disease-19 (COVID-19) can induce severe inflammation of the lungs and respiratory system. Severe COVID-19 is frequently associated with hyper inflammation and hyper-ferritinemia. High iron levels are known to trigger pro-inflammatory effects. Cumulative iron loading negatively impacts on a patients innate immune effector functions and increases the risk for infection related complications. Prognosis of severe acute respiratory SARS-CoV-2 patients may be impacted by iron excess. Iron is an essential co-factor for numerous essential cellular enzymes and vital cellular operations. Viruses hijack cells in order to replicate, and efficient replication requires an iron-replete host. Utilizing iron loaded cells in culture we evaluated their susceptibility to infection by pseudovirus expressing the SARS-CoV-2 spike protein and resultant cellular inflammatory response. We observed that, high levels of iron enhanced host cell ACE2 receptor expression contributing to higher infectivity of pseudovirus. In vitro Cellular iron overload also synergistically enhanced the levels of; reactive oxygen species, reactive nitrogen species, pro-inflammatory cytokines (IL-1β, IL-6, IL-8 & TNF-α) and chemokine (CXCL-1&CCL-4) production in response to inflammatory stimulation of cells with spike protein. These results were confirmed using an in vivo mouse model. In future, limiting iron levels may be a promising adjuvant strategy in treating viral infection.
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Affiliation(s)
| | - Rahul Dilawari
- Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh, 160036, India
| | - Radheshyam Modanwal
- Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh, 160036, India
| | - Sharmila Talukdar
- Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh, 160036, India
| | - Asmita Dhiman
- Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh, 160036, India
| | - Chaaya Iyengar Raje
- National Institute of Pharmaceutical Education & Research, Phase X, Sector 67, SAS Nagar, Punjab, 160062, India
| | - Manoj Raje
- Institute of Microbial Technology, CSIR, Sector 39A, Chandigarh, 160036, India.
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16
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Pasquier G. COVID-19-associated mucormycosis in India: Why such an outbreak? J Mycol Med 2023; 33:101393. [PMID: 37182234 PMCID: PMC10168193 DOI: 10.1016/j.mycmed.2023.101393] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 04/17/2023] [Accepted: 05/03/2023] [Indexed: 05/16/2023]
Abstract
An unprecedented mucormycosis outbreak occurred in India during the second COVID-19 wave in spring 2021. COVID-19-associated mucormycosis (CAM) was observed, mainly rhino-orbito-cerebral mucormycosis (ROCM), in patients with poorly controlled diabetes and treated with inappropriate doses of glucocorticoids. The aim of this mini-review was to compare the characteristics of the CAM epidemic in India with (i) mucormycosis cases before the COVID-19 pandemic and (ii) CAM in the rest of the world (particularly in France) in order to identify the reasons for this outbreak. In India, the major mucormycosis epidemiologic change during the COVID-19 pandemic was an increase in the percentage of patients treated with corticosteroids who developed CAM. Compared with the rest of the world, India reported a higher mucormycosis incidence even before the COVID-19 pandemic. Moreover, in India, patients with CAM were more likely to have diabetes mellitus and ROCM; conversely, mortality rates were lower. The reasons for such a localized epidemic in India have remained unclear, but some hypotheses can be put forward, particularly the combination of high prevalence of uncontrolled diabetes mellitus and frequent indiscriminate corticosteroid utilization in a country that already had a high mucormycosis burden before the COVID-19 pandemic.
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Affiliation(s)
- Gregoire Pasquier
- University of Montpellier, CNRS, IRD, Academic Hospital (CHU) of Montpellier, MiVEGEC, Department of Parasitology/Mycology, Département de Parasitologie-Mycologie, CHU de Montpellier, Site Antonin BALMES/La Colombiere, 39 avenue Charles FLAHAULT - 34295 Montpellier Cedex 5, Tel Laboratoire Hospitalier, Montpellier, France.
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17
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Lefebvre T, Boutten A, Raulet-Bussian C, Raynor A, Manceau H, Puy H, Moulouel B, Schmitt C, Timsit JF, Lefort A, Weiss E, Lescure FX, Ricard JD, Sonneville R, Peoc'h K. Evaluation of iron metabolism in hospitalized COVID-19 patients. Clin Chim Acta 2023; 548:117509. [PMID: 37549821 DOI: 10.1016/j.cca.2023.117509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 07/25/2023] [Accepted: 08/04/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. METHODS We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. RESULTS Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 μmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. CONCLUSION Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.
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Affiliation(s)
- Thibaud Lefebvre
- Centre Français des Porphyries, Hôpital Louis Mourier, DMU BIOGEM, APHP, Colombes, France; Université Paris Cité, Centre de Recherche sur l'Inflammation, INSERM, UMR1149, Laboratoire d'Excellence GR-Ex, Paris, France
| | - Anne Boutten
- Service de Biochimie, Hôpital Bichat, DMU BIOGEM, AP-HP, Paris, France
| | | | - Alexandre Raynor
- Service de Biochimie, Hôpital Bichat, DMU BIOGEM, AP-HP, Paris, France
| | - Hana Manceau
- Université Paris Cité, Centre de Recherche sur l'Inflammation, INSERM, UMR1149, Laboratoire d'Excellence GR-Ex, Paris, France; Service de Biochimie, Hôpital Beaujon, DMU BIOGEM AP-HP, Clichy, France
| | - Hervé Puy
- Centre Français des Porphyries, Hôpital Louis Mourier, DMU BIOGEM, APHP, Colombes, France; Université Paris Cité, Centre de Recherche sur l'Inflammation, INSERM, UMR1149, Laboratoire d'Excellence GR-Ex, Paris, France; Service de Biochimie, Hôpital Bichat, DMU BIOGEM, AP-HP, Paris, France
| | - Boualem Moulouel
- Centre Français des Porphyries, Hôpital Louis Mourier, DMU BIOGEM, APHP, Colombes, France
| | - Caroline Schmitt
- Centre Français des Porphyries, Hôpital Louis Mourier, DMU BIOGEM, APHP, Colombes, France; Université Paris Cité, Centre de Recherche sur l'Inflammation, INSERM, UMR1149, Laboratoire d'Excellence GR-Ex, Paris, France
| | - Jean-François Timsit
- Université Paris Cité, Hôpital Bichat, Service de Médecine Intensive Réanimation, DMU INVICTUS, Paris, IAME, UMR1148, INSERM, Paris, France
| | - Agnès Lefort
- Université Paris Cité, APHP, Service de médecine interne, DMU INVICTUS, Hopital Beaujon, IAME, INSERM UMR 1137, INSERM Paris, France
| | - Emmanuel Weiss
- Université Paris Cité, AP-HP, Hôpital Beaujon, DMU PARABOL, Service de Médecine Intensive Réanimation, Clichy, IAME, UMR1137, INSERM, Paris, France
| | - Francois-Xavier Lescure
- Université Paris Cité, AP-HP, Hôpital Bichat, DMU INVICTUS, Service des Maladies Infectieuses, Paris, IAME, UMR1137, INSERM, Paris, France
| | - Jean-Damien Ricard
- Université Paris Cité, AP-HP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, IAME, UMR1137, INSERM, Paris, France
| | - Romain Sonneville
- Université Paris Cité, Hôpital Bichat, Service de Médecine Intensive Réanimation, DMU INVICTUS, Paris, IAME, UMR1148, INSERM, Paris, France
| | - Katell Peoc'h
- Université Paris Cité, Centre de Recherche sur l'Inflammation, INSERM, UMR1149, Laboratoire d'Excellence GR-Ex, Paris, France; Service de Biochimie, Hôpital Bichat, DMU BIOGEM, AP-HP, Paris, France; Service de Biochimie, Hôpital Beaujon, DMU BIOGEM AP-HP, Clichy, France.
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18
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Marino L, Criniti A, Guida S, Bucci T, Ballesio L, Suppa M, Galardo G, Vacca A, Santulli M, Angeloni A, Lubrano C, Gandini O. Interleukin 18 and IL-18 BP response to Sars-CoV-2 virus infection. Clin Exp Med 2023; 23:1243-1250. [PMID: 36385417 PMCID: PMC9668240 DOI: 10.1007/s10238-022-00943-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 11/05/2022] [Indexed: 11/17/2022]
Abstract
The immune response to the SARS-CoV-2 infection is crucial to the patient outcome. IL-18 is involved in the lymphocyte response to the disease and it is well established its important role in the complex developing of the host response to viral infection. This study aims at the analysis of the concentrations of IL-18, IL-18BP, INF-γ at the onset of the SARS-CoV-2 infection. The serum levels of measured interleukins were obtained through enzyme-linked immunosorbent assay. Furthermore, the free fraction of IL-18 was numerically evaluated. The enrolled patients were divided in two severity groups according to a threshold value of 300 for the ratio of arterial partial pressure of oxygen and fraction of inspired oxygen fraction and according to the parenchymal involvement as evaluated by computerized tomography at the admittance. In the group of patients with a more severe disease, a significant increase of the IL-18, INF-γ and IL-18BP levels have been observed, whereas the free IL-18 component values were almost constant. The results confirm that, at the onset of the disease, the host response keep the inflammatory cytokines in an equilibrium and support the hypothesis to adopt the IL-18BP modulation as a possible and effective therapeutic approach.
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Affiliation(s)
- Luca Marino
- Emergency Medicine Unit, Department of Emergency‐Acceptance, Critical Areas and Trauma, Policlinico “Umberto I”, 00161 Rome, Italy
- Department of Mechanical and Aerospace Engineering, “Sapienza” University of Rome, 00168 Rome, Italy
| | - Anna Criniti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Sofia Guida
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Tommaso Bucci
- Department of General Surgery and Surgical Specialties “Paride Stefanini”, Sapienza University of Rome, Rome, Italy
| | - Laura Ballesio
- Department of Radiology, Anatomo-Pathology and Oncology, Sapienza University of Rome, Rome, Italy
| | - Marianna Suppa
- Emergency Medicine Unit, Department of Emergency‐Acceptance, Critical Areas and Trauma, Policlinico “Umberto I”, 00161 Rome, Italy
| | - Gioacchino Galardo
- Department of General Surgery and Surgical Specialties “Paride Stefanini”, Sapienza University of Rome, Rome, Italy
| | - Alessandra Vacca
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Maria Santulli
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Antonio Angeloni
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Carla Lubrano
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Orietta Gandini
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
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19
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Fiorino S, Carusi A, Zappi A, Tateo F, Peruzzo L, Zanardi M, Savelli F, Di Marzio G, Cesaretti S, Dazzani F, Francesconi R, Leandri P, Tortorici G, Vicari S, Melucci D, Lari F. Characteristics, comorbidities and laboratory measures associated with disease severity and poor prognosis in young and elderly patients with COVID-19 admitted to medical wards in Emilia-Romagna region, Italy: a multicentre retrospective study. ITALIAN JOURNAL OF MEDICINE 2023; 17. [DOI: 10.4081/itjm.2023.1608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Background and Objectives. A relatively small number of studies have investigated the characteristics, comorbidities and laboratory measures associated with prognosis in patients with COVID-19, admitted to Internal Medicine Units (IMU) in Italy. Therefore, we performed a retrospective multicentre study to identify baseline features, predisposing to severe disease and poor outcomes, in adult individuals with SARS-CoV-2 infection, hospitalized in 5 IMUs in the Emilia-Romagna region (Italy). Materials and Methods. We included 129 consecutive patients (male 75, median age 68 years) from 1st March 2020 to 31st October 2021. Patients’ baseline characteristics, comorbidities, laboratory measures, and outcomes were collected. Results. At admission, the factors significantly associated with a higher risk of in-hospital mortality included: age (median 68 vs. 83 years in survived vs. dead patients, P=0.000), diabetes [Odds Ratio (OR) 4.00, P=0.016], chronic obstructive pulmonary disease (OR 4.60, P=0.022), cancer (OR 5.81, P=0.021), acute- (OR 9.88, P=0.000) and chronic-renal failure (OR 6.76, P=0.004). During the study period, 16 individuals died (12.4%), all over 70 years old. In deceased vs. non-deceased patients were detected: i) more elevated white blood cells and neutrophils-counts and lower lymphocytes count; ii) higher levels of total/direct bilirubin, creatinine, C-reactive-protein, lactate-dehydrogenase, ferritin, but only a slight Interleukin-6 increase; iii) a trend of lower vitamin D values. Conclusions. We proposed a new I index, a modified form of the Age-Adjusted Charlson Comorbidity Index, by considering pO2/FiO2 ratio, to better characterize the severity of COVID-19. Furthermore, we critically discuss our results with the current assumption which considers COVID-19 as a pathological condition associated with cytokine storm.
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20
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Ruscitti P, Ursini F, Shoenfeld Y. Ferritin and myalgic encephalomyelitis/chronic fatigue syndrome in post COVID-19, an unexpected facet of the hyperferritinemic syndrome? J Psychosom Res 2023; 169:111231. [PMID: 36959046 PMCID: PMC10028614 DOI: 10.1016/j.jpsychores.2023.111231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 03/06/2023] [Accepted: 03/12/2023] [Indexed: 03/24/2023]
Affiliation(s)
- Piero Ruscitti
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, delta 6 building, PO Box 67100, L'Aquila, Italy.
| | - Francesco Ursini
- Medicine & Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli (IOR), 40136 Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40125 Bologna, Italy
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel HaShomer 5265601, Israel; Sackler Faculty of Medicine, Ariel University, Ariel 40700, Israel; Laboratory of the Mosaic of Autoimmunity, Saint-Petersburg State University, 199034 St. Petersburg, Russia
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21
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Li Q, Chen Z, Zhou X, Li G, Zhang C, Yang Y. Ferroptosis and multi-organ complications in COVID-19: mechanisms and potential therapies. Front Genet 2023; 14:1187985. [PMID: 37303950 PMCID: PMC10250669 DOI: 10.3389/fgene.2023.1187985] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 05/17/2023] [Indexed: 06/13/2023] Open
Abstract
COVID-19 is an infectious disease caused by SARS-CoV-2, with respiratory symptoms as primary manifestations. It can progress to severe illness, leading to respiratory failure and multiple organ dysfunction. Recovered patients may experience persistent neurological, respiratory, or cardiovascular symptoms. Mitigating the multi-organ complications of COVID-19 has been highlighted as a crucial part of fighting the epidemic. Ferroptosis is a type of cell death linked to altered iron metabolism, glutathione depletion, glutathione peroxidase 4 (GPX4) inactivation, and increased oxidative stress. Cell death can prevent virus replication, but uncontrolled cell death can also harm the body. COVID-19 patients with multi-organ complications often exhibit factors related to ferroptosis, suggesting a possible connection. Ferroptosis inhibitors can resist SARS-CoV-2 infection from damaging vital organs and potentially reduce COVID-19 complications. In this paper, we outline the molecular mechanisms of ferroptosis and, based on this, discuss multi-organ complications in COVID-19, then explore the potential of ferroptosis inhibitors as a supplementary intervention for COVID-19. This paper will provide a reference for the possible treatment of SARS-CoV-2 infected disease to reduce the severity of COVID-19 and its subsequent impact.
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Affiliation(s)
- Qi Li
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zeyuan Chen
- Department of Pharmacy, Luxian People’s Hospital, Luzhou, China
| | - Xiaoshi Zhou
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Guolin Li
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Changji Zhang
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Yong Yang
- Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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22
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Kumari A, Ranjan A, Nishant P, Sinha S, Sinha RK. Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India. Indian J Ophthalmol 2023; 71:2193-2198. [PMID: 37202947 PMCID: PMC10391476 DOI: 10.4103/ijo.ijo_2507_22] [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: 09/30/2022] [Revised: 02/01/2023] [Accepted: 02/07/2023] [Indexed: 05/20/2023] Open
Abstract
PURPOSE The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. METHODS This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. RESULTS There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). CONCLUSION Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.
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Affiliation(s)
- Abhilasha Kumari
- Department of Ophthalmology, Patna Medical College, Patna, India
| | - Alok Ranjan
- Department of Ophthalmology, Patna Medical College, Patna, India
| | - Prateek Nishant
- Department of Ophthalmology, All India Institute of Medical Sciences, Patna, India
| | - Sony Sinha
- Department of Ophthalmology, Patna Medical College, Patna, India
| | - Ranjeet K Sinha
- Department of Community Medicine, Patna Medical College, Patna, India
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23
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Abdul Hussein TA, Fadhil HY. Impact of inflammatory markers, dread diseases and cycle threshold (Ct) Values in COVID-19 progression. BIONATURA 2023. [DOI: 10.21931/rb/2023.08.01.33] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023] Open
Abstract
The link between the inflammatory marker and SARS-CoV-2 cycle threshold (Ct) with disease progression remains undefined, mainly in coronavirus disease-2019 (COVID-19). Therefore, this study aimed to identify several inflammatory markers (Ferritin, LDH, and D-dimer), and Ct values to predict outcomes in hospitalized COVID-19 Iraqi patients. A case study was performed on 426 patients to guess cutoff values of inflammatory markers that were detected by a real-time polymerase chain reaction (RT-PCR) and specific auto-analyzer instrument. Significantly increased levels of inflammatory markers in critical and severe patients compared with mild-moderate (p < 0.001). Compared with aging and disease severity, inflammatory markers and Ct values are significantly related to the aging and severity in critical and severe COVID-19 patients (p < 0.001). Finding the Ct value was negatively associated with Ferritin, LDH, and D-dimer (p < 0.001); moreover, inflammatory markers concentrations and Ct values were significantly higher during the first ten days. The Ct values correlate with some relevant clinical parameters of inflammation. Higher levels of D dimer, S. Ferritin and LDH were associated with older age and the severity of COVID-19. The area under the ROC curve indicates that serum ferritin was the highest and excellent predictor for disease severity.
Keywords: Coronavirus disease 2019; Inflammation; D-dimer; Ferritin; Lactate dehydrogenase; Cycle threshold (Ct).
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Affiliation(s)
- Thaer A. Abdul Hussein
- Department of Biology, College of Science, University of Baghdad, Al-Jadriya, Baghdad, Iraq
| | - Hula Y. Fadhil
- Department of Biology, College of Science, University of Baghdad, Al-Jadriya, Baghdad, Iraq
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24
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Berardicurti O, Navarini L, Vomero M, Currado D, Biaggi A, Marino A, Bearzi P, Corberi E, Rigon A, Arcarese L, Vadacca M, Mattei A, Agrò FE, Incalzi RA, Sambuco F, Travaglino F, Ruscitti P, Cipriani P, Giacomelli R. The similar expression of both ferritin and scavenger receptors activation genes in patients with COVID19 and AOSD support their role in the pathogenesis of these diseases and identify a common mechanism at the basis of the "hyperferritinemic syndromes". Autoimmun Rev 2023; 22:103309. [PMID: 36889656 PMCID: PMC9986116 DOI: 10.1016/j.autrev.2023.103309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023]
Abstract
A role for COVID19 in "hyperferritinemic syndromes" has been proposed based on its clinical and serological characteristics and its similarities with AOSD. To better understand the molecular pathways responsible of these similarities, we evaluated in the PBMCs of 4 active AOSD patients, 2 COVID19 patients with ARDS, and 2 HCs the expression of genes associated with iron metabolisms, with monocyte/macrophages activation, and finally with NETs formation.
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Affiliation(s)
- Onorina Berardicurti
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy; Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy.
| | - Luca Navarini
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy; Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Marta Vomero
- Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Damiano Currado
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy; Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Alice Biaggi
- Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Annalisa Marino
- Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Pietro Bearzi
- Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Erika Corberi
- Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
| | - Amelia Rigon
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Luisa Arcarese
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Marta Vadacca
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Alessia Mattei
- Operative Research Unit of Anaesthesia, Intensive Care and Pain Management, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy
| | - Felice Eugenio Agrò
- Operative Research Unit of Anaesthesia, Intensive Care and Pain Management, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy; Anesthesia, Intensive Care and Pain Management, Department of Medicine, University of Rome "Campus Bio-Medico", Rome, Italy
| | - Raffaele Antonelli Incalzi
- Unit of Geriatrics, Campus Bio-Medico University of Rome, Rome, Italy; Internal Medicine, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128, Rome, Italy
| | - Federica Sambuco
- Emergency Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Francesco Travaglino
- Emergency Department, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Piero Ruscitti
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Paola Cipriani
- Rheumatology Unit, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Roberto Giacomelli
- Clinical and Research Section of Rheumatology and Clinical Immunology, Fondazione Policiclinico Campus Biomedico, Via Alvaro del Portillo 200, 00128 Rome, Italy; Rheumatology and Clinical Immunology, Department of Medicine, University of Rome "Campus Biomedico", School of Medicine, Rome, Italy
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25
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Kottarathil M, Thayanidhi P, P S, Jyoti Kindo A. Rise of mucormycosis during the COVID-19 pandemic and the challenges faced. Curr Med Mycol 2023; 9:44-55. [PMID: 37867589 PMCID: PMC10590187 DOI: 10.18502/cmm.2023.345032.1400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 07/14/2023] [Accepted: 07/15/2023] [Indexed: 10/24/2023] Open
Abstract
Mucormycosis (previously called zygomycosis) is a diverse group of increasingly recognized and frequently fatal mycotic diseases caused by members of the class zygomycetes. Mucormycosis is around 80 times more common in India, compared to other developed countries, with a frequency of 0.14 cases per 1,000 population. The most frequent causative agent of mucormycosis is the following genera from the Order Mucorales Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea. The major risk factors for the development of mucormycosis are diabetic ketoacidosis, deferoxamine treatment, cancer, solid organ or bone marrow transplantations, prolonged steroid use, extreme malnutrition, and neutropenia. The common clinical forms of mucormycosis are rhino-orbital-cerebral, pulmonary, cutaneous, and gastrointestinal. During the second wave of COVID-19, there was a rapid increase in mucormycosis with more severity than before. Amphotericin B is currently found to be an effective drug as it is found to have a broad-spectrum activity and posaconazole is used as a salvage therapy. Newer triazole isavuconazole is also found effective against mucormycosis. This study aimed to review various studies on the laboratory diagnosis and treatment of mucormycosis.
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Affiliation(s)
- Malavika Kottarathil
- Department of Microbiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Premamalini Thayanidhi
- Department of Microbiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Sathyamurthy P
- Department of General Medicine, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
| | - Anupma Jyoti Kindo
- Department of Microbiology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
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26
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Huyut MT, Huyut Z. Effect of ferritin, INR, and D-dimer immunological parameters levels as predictors of COVID-19 mortality: A strong prediction with the decision trees. Heliyon 2023; 9:e14015. [PMID: 36919085 PMCID: PMC9985543 DOI: 10.1016/j.heliyon.2023.e14015] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 01/25/2023] [Accepted: 02/17/2023] [Indexed: 03/07/2023] Open
Abstract
Background and objective A hyperinflammatory environment is thought to be the distinctive characteristic of COVID-19 infection and an important mediator of morbidity. This study aimed to determine the effect of other immunological parameter levels, especially ferritin, as a predictor of COVID-19 mortality via decision-trees analysis. Material and method This is a retrospective study evaluating a total of 2568 patients who died (n = 232) and recovered (n = 2336) from COVID-19 in August and December 2021. Immunological laboratory data were compared between two groups that died and recovered from patients with COVID-19. In addition, decision trees from machine learning models were used to evaluate the performance of immunological parameters in the mortality of the COVID-19 disease. Results Non-surviving from COVID-19 had 1.75 times higher ferritin, 10.7 times higher CRP, 2.4 times higher D-dimer, 1.14 times higher international-normalized-ratio (INR), 1.1 times higher Fibrinogen, 22.9 times higher procalcitonin, 3.35 times higher troponin, 2.77 mm/h times higher erythrocyte-sedimentation-rate (ESR), 1.13sec times longer prothrombin time (PT) when compared surviving patients. In addition, our interpretable decision tree, which was constructed with only the cut-off values of ferritin, INR, and D-dimer, correctly predicted 99.7% of surviving patients and 92.7% of non-surviving patients. Conclusions This study perfectly predicted the mortality of COVID-19 with our interpretable decision tree constructed with INR and D-dimer, especially ferritin. For this reason, we think that it may be important to include ferritin, INR, and D-dimer parameters and their cut-off values in the scoring systems to be planned for COVID-19 mortality.
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Affiliation(s)
- Mehmet Tahir Huyut
- Erzincan Binali Yıldırım University, Faculty of Medicine, Department of Biostatistics and Medical Informatics, Erzincan, Turkey
| | - Zübeyir Huyut
- Van Yuzuncu Yıl University, Faculty of Medicine, Department of Biochemistry, Van, Turkey
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27
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Dam P, Cardoso MH, Mandal S, Franco OL, Sağıroğlu P, Polat OA, Kokoglu K, Mondal R, Mandal AK, Ocsoy I. Surge of mucormycosis during the COVID-19 pandemic. Travel Med Infect Dis 2023; 52:102557. [PMID: 36805033 PMCID: PMC9940844 DOI: 10.1016/j.tmaid.2023.102557] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/07/2022] [Accepted: 02/15/2023] [Indexed: 02/22/2023]
Abstract
Patients with respiratory viral infections are more likely to develop co-infections leading to increased fatality. Mucormycosis is an epidemic amidst the COVID-19 pandemic that conveys a 'double threat' to the global health fraternity. Mucormycosis is caused by the Mucorales group of fungi and exhibits acute angioinvasion generally in immunocompromised patients. The most familiar foci of infections are sinuses (39%), lungs (24%), and skin tissues (19%) where the overall dissemination occurs in 23% of cases. The mortality rate in the case of disseminated mucormycosis is found to be 96%. Symptoms are mostly nonspecific and often resemble other common bacterial or fungal infections. Currently, COVID-19-associated mucormycosis (CAM) is being reported from a number of countries such as the USA, Turkey, France, Mexico, Iran, Austria, UK, Brazil, and Italy, while India is the hotspot for this deadly co-infection, accounting for approximately 28,252 cases up to June 8, 2021. It strikes patients within 12-18 days after COVID-19 recovery, and nearly 80% require surgery. Nevertheless, the mortality rate can reach 94% if the diagnosis is delayed or remains untreated. Sometimes COVID-19 is the sole predisposing factor for CAM. Therefore, this study may provide a comprehensive resource for clinicians and researchers dealing with fungal infections, intending to link the potential translational knowledge and prospective therapeutic challenges to counter this opportunistic pathogen.
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Affiliation(s)
- Paulami Dam
- Chemical Biology Laboratory, Department of Sericulture, Raiganj University, North Dinajpur, West Bengal, 733134, India
| | - Marlon H Cardoso
- S-inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Brazil; Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, Brazil; Instituto de Biociências (INBIO), Universidade Federal de Mato Grosso do Sul, Cidade Universitária, Campo Grande, Mato Grosso do Sul, Brazil
| | - Sukhendu Mandal
- Laboratory of Molecular Bacteriology, Department of Microbiology, University of Calcutta, 700019, India
| | - Octávio L Franco
- S-inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, Brazil; Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, Brazil
| | - Pınar Sağıroğlu
- Department of Medical Microbiology, School of Medicine, Erciyes University, Kayseri, Turkey
| | | | - Kerem Kokoglu
- Department of Otolaryngology, Erciyes University School of Medicine, Kayseri, Turkey
| | - Rittick Mondal
- Chemical Biology Laboratory, Department of Sericulture, Raiganj University, North Dinajpur, West Bengal, 733134, India
| | - Amit Kumar Mandal
- Chemical Biology Laboratory, Department of Sericulture, Raiganj University, North Dinajpur, West Bengal, 733134, India; Centre for Nanotechnology Science (CeNS), Raiganj University, North Dinajpur, West Bengal, 733134, India.
| | - Ismail Ocsoy
- Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, 38039, Turkey.
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28
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Mohammadi AH, Behjati M, Karami M, Abari AH, Sobhani-Nasab A, Rourani HA, Hazrati E, Mirghazanfari SM, Hadi V, Hadi S, Milajerdi A. An overview on role of nutrition on COVID-19 immunity: Accumulative review from available studies. CLINICAL NUTRITION OPEN SCIENCE 2023; 47:6-43. [PMID: 36540357 PMCID: PMC9754583 DOI: 10.1016/j.nutos.2022.11.001] [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: 04/13/2022] [Accepted: 11/03/2022] [Indexed: 11/11/2022] Open
Abstract
The novel coronavirus infection (COVID-19) conveys a serious global threat to health and economy. A common predisposing factor for development to serious progressive disease is presence of a low-grade inflammation, e.g., as seen in diabetes, metabolic syndrome, and heart failure. Micronutrient deficiencies may also contribute to the development of this state. Therefore, the aim of the present study is to explore the role of the nutrition to relieve progression of COVID-19. According PRISMA protocol, we conducted an online databases search including Scopus, PubMed, Google Scholar and web of science for published literatures in the era of COVID-19 Outbreak regarding to the status of nutrition and COVID-19 until December 2021. There were available studies (80 studies) providing direct evidence regarding the associations between the status of nutrition and COVID-19 infection. Adequate nutritional supply is essential for resistance against other viral infections and also for improvement of immune function and reduction of inflammation. Hence, it is suggested that nutritional intervention which secures an adequate status might protect against the novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome - coronavirus-2) and mitigate its course. We also recommend initiation of adequate nutritional supplementation in high-risk areas and/or soon after the time of suspected infection with SARS-CoV-2. Subjects in high-risk groups should have high priority for applying this nutritive adjuvant therapy that should be started prior to administration of specific and supportive medical measures.
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Affiliation(s)
- Amir Hossein Mohammadi
- Department of Biochemistry, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Mohaddeseh Behjati
- Cellular, Molecular and Genetics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoumeh Karami
- Department of Biochemistry, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Afrouzossadat Hosseini Abari
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran
| | - Ali Sobhani-Nasab
- Social Determinants of Health (SDH) Research Center, Kashan University of Medical Sciences, Kashan, Iran
- Core Research Lab, Kashan University of Medical Sciences, Kashan, Iran
| | - Hamed Amini Rourani
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, Iran
| | - Ebrahim Hazrati
- Trauma Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Sayid Mahdi Mirghazanfari
- Department of Physiology and Iranian Medicine, School of Medicine, AJA University of Medical Sciences, Iran
| | - Vahid Hadi
- Department of Health, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Saeid Hadi
- Department of Health, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Alireza Milajerdi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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29
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Hortová-Kohoutková M, Skotáková M, Onyango IG, Slezáková M, Panovský R, Opatřil L, Slanina P, De Zuani M, Mrkva O, Andrejčinová I, Lázničková P, Dvončová M, Mýtniková A, Ostland V, Šitina M, Stokin GB, Šrámek V, Vlková M, Helán M, Frič J. Hepcidin and ferritin levels as markers of immune cell activation during septic shock, severe COVID-19 and sterile inflammation. Front Immunol 2023; 14:1110540. [PMID: 36776891 PMCID: PMC9911830 DOI: 10.3389/fimmu.2023.1110540] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 01/28/2023] Open
Abstract
Introduction Major clinically relevant inflammatory events such as septic shock and severe COVID-19 trigger dynamic changes in the host immune system, presenting promising candidates for new biomarkers to improve precision diagnostics and patient stratification. Hepcidin, a master regulator of iron metabolism, has been intensively studied in many pathologies associated with immune system activation, however these data have never been compared to other clinical settings. Thus, we aimed to reveal the dynamics of iron regulation in various clinical settings and to determine the suitability of hepcidin and/or ferritin levels as biomarkers of inflammatory disease severity. Cohorts To investigate the overall predictive ability of hepcidin and ferritin, we enrolled the patients suffering with three different diagnoses - in detail 40 patients with COVID-19, 29 patients in septic shock and eight orthopedic patients who were compared to nine healthy donors and all cohorts to each other. Results We showed that increased hepcidin levels reflect overall immune cell activation driven by intrinsic stimuli, without requiring direct involvement of infection vectors. Contrary to hepcidin, ferritin levels were more strongly boosted by pathogen-induced inflammation - in septic shock more than four-fold and in COVID-19 six-fold in comparison to sterile inflammation. We also defined the predictive capacity of hepcidin-to-ferritin ratio with AUC=0.79 and P = 0.03. Discussion Our findings confirm that hepcidin is a potent marker of septic shock and other acute inflammation-associated pathologies and demonstrate the utility of the hepcidin-to-ferritin ratio as a predictor of mortality in septic shock, but not in COVID-19.
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Affiliation(s)
| | - Monika Skotáková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Isaac G. Onyango
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Miriam Slezáková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Roman Panovský
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,1st Department of Internal Medicine/Cardioangiology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Lukáš Opatřil
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,1st Department of Internal Medicine/Cardioangiology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Peter Slanina
- Institute of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Marco De Zuani
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Ondřej Mrkva
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Ivana Andrejčinová
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Petra Lázničková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia
| | - Martina Dvončová
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Alexandra Mýtniková
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | | | - Michal Šitina
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Gorazd B. Stokin
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Celica BIOMEDICAL, Ljubljana, Slovenia,Division of Neurology, University Medical Centre, Ljubljana, Slovenia
| | - Vladimír Šrámek
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Marcela Vlková
- Institute of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Martin Helán
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Department of Anesthesiology and Intensive Care, Faculty of Medicine, Masaryk University, Brno, Czechia
| | - Jan Frič
- International Clinical Research Center, St. Anne’s University Hospital, Brno, Czechia,Department of Modern Immunotherapy, Institute of Hematology and Blood Transfusion, Prague, Czechia,*Correspondence: Jan Frič,
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30
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Chen J, He ZX, Wang FK. RETRACTED ARTICLE: Evaluation of ferritin level in COVID-19 patients and its inflammatory response. APPLIED NANOSCIENCE 2023; 13:3121. [PMID: 35136706 PMCID: PMC8812356 DOI: 10.1007/s13204-021-02115-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 09/24/2021] [Indexed: 01/08/2023]
Affiliation(s)
- Jing Chen
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Zheng-Xin He
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
| | - Fun-Kun Wang
- Department of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force, Shijiazhuang, 050082 China
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Naidu SAG, Clemens RA, Naidu AS. SARS-CoV-2 Infection Dysregulates Host Iron (Fe)-Redox Homeostasis (Fe-R-H): Role of Fe-Redox Regulators, Ferroptosis Inhibitors, Anticoagulants, and Iron-Chelators in COVID-19 Control. J Diet Suppl 2023; 20:312-371. [PMID: 35603834 DOI: 10.1080/19390211.2022.2075072] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Severe imbalance in iron metabolism among SARS-CoV-2 infected patients is prominent in every symptomatic (mild, moderate to severe) clinical phase of COVID-19. Phase-I - Hypoxia correlates with reduced O2 transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Phase-II - Hyperferritinemia results from an increased iron overload, which triggers a fulminant proinflammatory response - the acute cytokine release syndrome (CRS). Elevated cytokine levels (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 patients. Phase-III - Thromboembolism is consequential to erythrocyte dysfunction with heme release, increased prothrombin time and elevated D-dimers, cumulatively linked to severe coagulopathies with life-threatening outcomes such as ARDS, and multi-organ failure. Taken together, Fe-R-H dysregulation is implicated in every symptomatic phase of COVID-19. Fe-R-H regulators such as lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, reduce oxidative stress, and improve host defense by optimizing iron metabolism. Due to its pivotal role in 'cytokine storm', ferroptosis is a potential intervention target. Ferroptosis inhibitors such as ferrostatin-1, liproxstatin-1, quercetin, and melatonin could prevent mitochondrial lipid peroxidation, up-regulate antioxidant/GSH levels and abrogate iron overload-induced apoptosis through activation of Nrf2 and HO-1 signaling pathways. Iron chelators such as heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid could protect against ferroptosis and restore mitochondrial function, iron-redox potential, and rebalance Fe-R-H status. Therefore, Fe-R-H restoration is a host biomarker-driven potential combat strategy for an effective clinical and post-recovery management of COVID-19.
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Affiliation(s)
| | - Roger A Clemens
- Department of International Regulatory Science, University of Southern California School of Pharmacy, Los Angeles, CA, USA
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Iron Deprivation by Oral Deferoxamine Application Alleviates Acute Campylobacteriosis in a Clinical Murine Campylobacter jejuni Infection Model. Biomolecules 2022; 13:biom13010071. [PMID: 36671455 PMCID: PMC9855827 DOI: 10.3390/biom13010071] [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: 11/08/2022] [Revised: 12/21/2022] [Accepted: 12/26/2022] [Indexed: 01/01/2023] Open
Abstract
The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10-/- mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis.
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Differential Diagnosis of Hyperferritinemia in Critically Ill Patients. J Clin Med 2022; 12:jcm12010192. [PMID: 36614993 PMCID: PMC9821140 DOI: 10.3390/jcm12010192] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/16/2022] [Accepted: 12/24/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Elevated serum ferritin is a common condition in critically ill patients. It is well known that hyperferritinemia constitutes a good biomarker for hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. However, further differential diagnoses of hyperferritinemia in adult critically ill patients remain poorly investigated. We sought to systematically investigate hyperferritinemia in adult critically ill patients without HLH. METHODS In this secondary analysis of a retrospective observational study, patients ≥18 years admitted to at least one adult intensive care unit at Charité-Universitätsmedizin Berlin between January 2006 and August 2018, and with hyperferritinemia of ≥500 μg/L were included. Patients with HLH were excluded. All patients were categorized into non-sepsis, sepsis, and septic shock. They were also classified into 17 disease groups, based on their ICD-10 codes, and pre-existing immunosuppression was determined. Uni- and multivariable linear regression analyses were performed in all patients. RESULTS A total of 2583 patients were analyzed. Multivariable linear regression analysis revealed positive associations of maximum SOFA score, sepsis or septic shock, liver disease (except hepatitis), and hematological malignancy with maximum ferritin. T/NK cell lymphoma, acute myeloblastic leukemia, Kaposi's sarcoma, acute or subacute liver failure, and hepatic veno-occlusive disease were positively associated with maximum ferritin in post-hoc multivariable linear regression analysis. CONCLUSIONS Sepsis or septic shock, liver disease (except hepatitis) and hematological malignancy are important differential diagnoses in hyperferritinemic adult critically ill patients without HLH. Together with HLH, they complete the quartet of important differential diagnoses of hyperferritinemia in adult critically ill patients. As these conditions are also related to HLH, it is important to apply HLH-2004 criteria for exclusion of HLH in hyperferritinemic patients. Hyperferritinemic critically ill patients without HLH require quick investigation of differential diagnoses.
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Jia FJ, Han J. Liver injury in COVID-19: Holds ferritinophagy-mediated ferroptosis accountable. World J Clin Cases 2022; 10:13148-13156. [PMID: 36683648 PMCID: PMC9850986 DOI: 10.12998/wjcc.v10.i36.13148] [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: 07/20/2022] [Revised: 11/20/2022] [Accepted: 12/08/2022] [Indexed: 12/26/2022] Open
Abstract
Even in patients without a history of liver disease, liver injury caused by coronavirus disease 2019 (COVID-19) is gradually becoming more common. However, the precise pathophysiological mechanisms behind COVID-19's liver pathogenicity are still not fully understood. We hypothesize that inflammation may become worse by cytokine storms caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Elevated ferritin levels can initiate ferritinophagy mediated by nuclear receptor coactivator 4 (NCOA4), which leads to iron elevation, and ferroptosis. In COVID-19 patients, ferroptosis can be restricted to reduce disease severity and liver damage by targeting NCOA4-mediated ferritinophagy. To confirm the role of ferritinophagy-mediated ferroptosis in SARS-CoV-2 infection, further research is required.
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Affiliation(s)
- Feng-Ju Jia
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Jing Han
- School of Nursing, Qingdao University, Qingdao 266071, Shandong Province, China
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Dufrusine B, Valentinuzzi S, Bibbò S, Damiani V, Lanuti P, Pieragostino D, Del Boccio P, D’Alessandro E, Rabottini A, Berghella A, Allocati N, Falasca K, Ucciferri C, Mucedola F, Di Perna M, Martino L, Vecchiet J, De Laurenzi V, Dainese E. Iron Dyshomeostasis in COVID-19: Biomarkers Reveal a Functional Link to 5-Lipoxygenase Activation. Int J Mol Sci 2022; 24:15. [PMID: 36613462 PMCID: PMC9819889 DOI: 10.3390/ijms24010015] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Revised: 12/13/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is characterized by a broad spectrum of clinical symptoms. After acute infection, some subjects develop a post-COVID-19 syndrome known as long-COVID. This study aims to recognize the molecular and functional mechanisms that occur in COVID-19 and long-COVID patients and identify useful biomarkers for the management of patients with COVID-19 and long-COVID. Here, we profiled the response to COVID-19 by performing a proteomic analysis of lymphocytes isolated from patients. We identified significant changes in proteins involved in iron metabolism using different biochemical analyses, considering ceruloplasmin (Cp), transferrin (Tf), hemopexin (HPX), lipocalin 2 (LCN2), and superoxide dismutase 1 (SOD1). Moreover, our results show an activation of 5-lipoxygenase (5-LOX) in COVID-19 and in long-COVID possibly through an iron-dependent post-translational mechanism. Furthermore, this work defines leukotriene B4 (LTB4) and lipocalin 2 (LCN2) as possible markers of COVID-19 and long-COVID and suggests novel opportunities for prevention and treatment.
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Affiliation(s)
- Beatrice Dufrusine
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Silvia Valentinuzzi
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Sandra Bibbò
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Verena Damiani
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Paola Lanuti
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
| | - Damiana Pieragostino
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Piero Del Boccio
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Department of Pharmacy, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Ersilia D’Alessandro
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Alberto Rabottini
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Alessandro Berghella
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
| | - Nerino Allocati
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Katia Falasca
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Claudio Ucciferri
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Francesco Mucedola
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Marco Di Perna
- Pneumology Department, “SS Annunziata” Hospital, 66100 Chieti, Italy
| | - Laura Martino
- Pneumology Department, “SS Annunziata” Hospital, 66100 Chieti, Italy
| | - Jacopo Vecchiet
- Department of Medicine and Aging Science, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
- Clinic of Infectious Diseases, S.S. Annunziata Hospital, 66100 Chieti, Italy
| | - Vincenzo De Laurenzi
- Department of Innovative Technologies in Medicine and Dentistry, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
| | - Enrico Dainese
- Department of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy
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Agrawal A, Kori N, Madhpuriya G, Nigam P, Agrawal S. Comparison of MRI Findings in Diabetic and Nondiabetic Patients with Rhino-Orbito-Cerebral Mucormycosis. ANNALS OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES (INDIA) 2022. [DOI: 10.1055/s-0042-1757740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Abstract
Objective Rhino-orbito-cerebral mucormycosis (ROCM) has emerged as a key concern during the period of coronavirus disease 2019 (COVID-19) pandemic. Diabetes mellitus is a known risk factor for invasive fungal infection. The aim of this article was to study and compare the radiological features of COVID-19-associated ROCM between diabetic and nondiabetic patients using magnetic resonance imaging.
Materials and Methods A retrospective observational study comprising 78 diabetics and 40 nondiabetics who developed ROCM after COVID-19 was conducted. The imaging data of both groups were analyzed, findings tabulated and compared using statistical methods.
Results Maxillary and ethmoid sinuses were commonly involved in both groups. Periantral fat and orbits were the most common sites of disease extension. The spread of infection to periantral soft tissue was significantly higher in diabetics (p = 0.049). Diabetics were more likely to have bone, orbit, and brain involvement than nondiabetics, although the difference was not statistically significant. Diabetic patients were the only ones to experience complications such as fungal abscess and cavernous sinus and internal carotid artery involvement. However, a considerable number of nondiabetic patients (22.5%) also had an intracranial extension of disease.
Conclusion The radiological appearances and common sites of invasion in ROCM are similar in diabetic and nondiabetic patients. The extensive spread of infection to extra-sinus regions can occur in nondiabetic patients with COVID-19 but is less frequent compared with diabetics.
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Affiliation(s)
- Alka Agrawal
- Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India
| | - Neetu Kori
- Department of Ophthalmology, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India
| | - Gulshan Madhpuriya
- Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India
| | - Prakhar Nigam
- Department of Radiodiagnosis, M.G.M. Medical College and M.Y. Hospital, Indore, Madhya Pradesh, India
| | - Simran Agrawal
- Dr. D. Y. Patil Medical College, Kolhapur, Maharashtra, India
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Chen Y, Ma ZF, Yu D, Jiang Z, Wang B, Yuan L. Geographical distribution of trace elements (selenium, zinc, iron, copper) and case fatality rate of COVID-19: a national analysis across conterminous USA. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2022; 44:4423-4436. [PMID: 35098416 PMCID: PMC8801196 DOI: 10.1007/s10653-022-01204-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 01/09/2022] [Indexed: 06/01/2023]
Abstract
Severe outcome particularly death is the largest burden of COVID-19. Clinical observations showed preliminary data that deficiency in certain trace elements, essential for the normal activity of immune system, may be associated with worse COVID-19 outcome. Relevant study of environmental epidemiology has yet to be explored. We investigated the geographical association between concentrations of Se, Zn, Fe and Cu in surface soils and case fatality rate of COVID-19 in USA. Two sets of database, including epidemiological data of COVID-19 (including case fatality rate, from the University of John Hopkinson) and geochemical concentration data of Se, Zn, Fe and Cu in surface soils (from the National Geochemical Survey), were mapped according to geographical location at the county level across conterminous USA. Characteristics of population, socio-demographics and residential environment by county were also collected. Seven cross-sectional sampling dates, with a 4-week interval between adjacent dates, constructed an observational investigation over 24 weeks from October 8, 2020, to March 25, 2021. Multivariable fractional (logit) outcome regression analyses were used to assess the association with adjustment for potential confounding factors. In USA counties with the lowest concentration of Zn, the case fatality rate of COVID-19 was the highest, after adjustment for other influencing factors. Associations of Se, Fe and Cu with case fatality rate of COVID-19 were either inconsistent over time or disappeared after adjustment for Zn. Our large study provides epidemiological evidence suggesting an association of Zn with COVID-19 severity, suggesting Zn deficiency should be avoided.
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Affiliation(s)
- Ying Chen
- Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China
| | - Zheng Feei Ma
- Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China
| | - Dahai Yu
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, ST5 5BG, UK
| | - Zifei Jiang
- Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China
| | - Bo Wang
- Suzhou Centre for Disease Control and Prevention, Suzhou, 215004, China
| | - Linxi Yuan
- Department of Health and Environmental Sciences, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China.
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Agrawal A, Tripathi PS, Shukla P, Nigam P, Kheti P. Intracranial manifestations of rhinocerebral mucormycosis: a pictorial essay. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2022. [PMCID: PMC9002219 DOI: 10.1186/s43055-022-00765-5] [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] [Indexed: 11/29/2022] Open
Abstract
Rhinocerebral mucormycosis has emerged as a common coinfection in coronavirus disease 2019 (COVID-19) patients during the convalescence period. Frequent spread of disease from sinonasal mucosa to bone, neck spaces, orbit, and brain occurs along the perivascular/perineural routes or through direct invasion. Brain involvement represents severe manifestation and is often associated with poor functional outcomes and high mortality rates. Magnetic resonance imaging (MRI) is the modality of choice for the intracranial assessment of disease severity in mucormycosis. Early and accurate identification of intracranial extension is imperative to improve survival rates. With this pictorial essay, we aim to familiarize the readers with the cross-sectional imaging features of intracranial complications of mucormycosis. The radiological details in this essay should serve as a broad checklist for radiologists and clinicians while dealing with this fulminant infection.
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Li C, Zhang Y, Xiao Y, Luo Y. Identifying the Effect of COVID-19 Infection in Multiple Myeloma and Diffuse Large B-Cell Lymphoma Patients Using Bioinformatics and System Biology. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:7017317. [PMID: 36466549 PMCID: PMC9711963 DOI: 10.1155/2022/7017317] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 11/05/2022] [Accepted: 11/12/2022] [Indexed: 09/29/2023]
Abstract
The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), also referred to as COVID-19, has spread to several countries and caused a serious threat to human health worldwide. Patients with confirmed COVID-19 infection spread the disease rapidly throughout the region. Multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) are risk factors for COVID-19, although the molecular mechanisms underlying the relationship among MM, DLBCL, and COVID-19 have not been elucidated so far. In this context, transcriptome analysis was performed in the present study to identify the shared pathways and molecular indicators of MM, DLBCL, and COVID-19, which benefited the overall understanding of the effect of COVID-19 in patients with MM and DLBCL. Three datasets (GSE16558, GSE56315, and GSE152418) were downloaded from the Gene Expression Omnibus (GEO) and searched for the shared differentially expressed genes (DEGs) in patients with MM and DLBCL who were infected with SARS-CoV-2. The objective was to detect similar pathways and prospective medicines. A total of 29 DEGs that were common across these three datasets were selected. A protein-protein interaction (PPI) network was constructed using data from the STRING database followed by the identification of hub genes. In addition, the association of MM and DLBCL with COVID-19 infection was analyzed through functional analysis using ontologies terms and pathway analysis. Three relationships were observed in the evaluated datasets: transcription factor-gene interactions, protein-drug interactions, and an integrated regulatory network of DEGs and miRNAs with mutual DEGs. The findings of the present study revealed potential pharmaceuticals that could be beneficial in the treatment of COVID-19.
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Affiliation(s)
- Chengcheng Li
- Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Institute of Life Science, Chongqing Medical University, Chongqing, China
| | - Ying Zhang
- Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yingying Xiao
- Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Institute of Life Science, Chongqing Medical University, Chongqing, China
| | - Yun Luo
- Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Giordano G, Teresa Bochicchio M, Niro G, Lucchesi A, Napolitano M. Genetic regulation of iron homeostasis in sideropenic patients with mild COVID-19 disease under a new oral iron formulation: Lessons from a different perspective. Immunobiology 2022; 227:152297. [PMID: 36327544 PMCID: PMC9597571 DOI: 10.1016/j.imbio.2022.152297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 10/04/2022] [Accepted: 10/21/2022] [Indexed: 11/05/2022]
Abstract
Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) needs iron to replicate itself. Coronaviruses are able to upregulate Chop/Gadd153 and Arg1 genes, consequently leading to CD8 lymphocytes decrease, degradation of asparagine and decreased nitric oxide (NO), thus impairing immune response and antithrombotic functions. Little is known about regulation of genes involved in iron metabolism in paucisymptomatic patients with COVID-19 disease or in patients with iron deficiency treated with sucrosomial iron. Methods Whole blood was taken from the COVID-19 patients and from patients with sideropenic anemia, treated or not (control group) with iron supplementations. Enrolled patients were: affected by COVID19 under sucrosomal iron support (group A), affected by COVID-19 not under oral iron support (group B), iron deficiency not under treatment, not affected by COVID19 (control group). After RNA extraction and complementary DNA (cDNA) synthesis of Arg1, Hepcidin and Chop/Gadd153, gene expression from the 3 groups was measured by qRT-PCR. M2 macrophages were detected by cytofluorimetry using CD163 and CD14 markers. Results Forty patients with COVID-19 (group A), 20 patients with iron deficiency treated with sucrosomial iron (group B) and 20 patients with iron deficiency not under treatment (control group) were enrolled. In all the patients supported with oral sucrosomial iron, the gene expression of Chop, Arg1 and Hepcidin genes was lower than in sideropenic patients not supported with iron, M1 macrophages polarization and functional iron deficiency was also lower in group A and B, than observed in the control group. Conclusions New oral iron formulations, as sucrosomial iron, are able to influence the expression of genes like Chop and Arg1 and to influence M2 macrophage polarization mainly in the early phase of COVID-19 disease.
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Affiliation(s)
- Giulio Giordano
- Division of Internal Medicine, Hematology Service, Regional Hospital “A. Cardarelli”, 86100 Campobasso, Italy
| | - Maria Teresa Bochicchio
- Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
| | - Giovanna Niro
- Division of Laboratory Medicine, Regional Hospital “A. Cardarelli”, 86100 Campobasso, Italy
| | - Alessandro Lucchesi
- Hematology Unit, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) “Dino Amadori”, Meldola (FC), Italy,Corresponding author
| | - Mariasanta Napolitano
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Haematology Unit, University Hospital “P. Giaccone”, University of Palermo, 90127 Palermo, Italy
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Adiguzel Y, Shoenfeld Y. Shared 6mer Peptides of Human and Omicron (21K and 21L) at SARS-CoV-2 Mutation Sites. Antibodies (Basel) 2022; 11:68. [PMID: 36412834 PMCID: PMC9680445 DOI: 10.3390/antib11040068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/18/2022] [Accepted: 10/21/2022] [Indexed: 12/14/2022] Open
Abstract
We investigated the short sequences involving Omicron 21K and Omicron 21L variants to reveal any possible molecular mimicry-associated autoimmunity risks and changes in those. We first identified common 6mers of the viral and human protein sequences present for both the mutant (Omicron) and nonmutant (SARS-CoV-2) versions of the same viral sequence and then predicted the binding affinities of those sequences to the HLA supertype representatives. We evaluated change in the potential autoimmunity risk, through comparative assessment of the nonmutant and mutant viral sequences and their similar human peptides with common 6mers and affinities to the same HLA allele. This change is the lost and the new, or de novo, autoimmunity risk, associated with the mutations in the Omicron 21K and Omicron 21L variants. Accordingly, e.g., the affinity of virus-similar sequences of the Ig heavy chain junction regions shifted from the HLA-B*15:01 to the HLA-A*01:01 allele at the mutant sequences. Additionally, peptides of different human proteins sharing 6mers with SARS-CoV-2 proteins at the mutation sites of interest and with affinities to the HLA-B*07:02 allele, such as the respective SARS-CoV-2 sequences, were lost. Among all, any possible molecular mimicry-associated novel risk appeared to be prominent in HLA-A*24:02 and HLA-B*27:05 serotypes upon infection with Omicron 21L. Associated disease, pathway, and tissue expression data supported possible new risks for the HLA-B*27:05 and HLA-A*01:01 serotypes, while the risks for the HLA-B*07:02 serotypes could have been lost or diminished, and those for the HLA-A*03:01 serotypes could have been retained, for the individuals infected with Omicron variants under study. These are likely to affect the complications related to cross-reactions influencing the relevant HLA serotypes upon infection with Omicron 21K and Omicron 21L.
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Affiliation(s)
- Yekbun Adiguzel
- Department of Medical Biology, School of Medicine, Atilim University, Ankara 06830, Turkey
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat-Gan 52621, Israel
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Bhar A, Gierse LC, Meene A, Wang H, Karte C, Schwaiger T, Schröder C, Mettenleiter TC, Urich T, Riedel K, Kaderali L. Application of a maximal-clique based community detection algorithm to gut microbiome data reveals driver microbes during influenza A virus infection. Front Microbiol 2022; 13:979320. [PMID: 36338082 PMCID: PMC9630851 DOI: 10.3389/fmicb.2022.979320] [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: 06/27/2022] [Accepted: 09/21/2022] [Indexed: 11/20/2022] Open
Abstract
Influenza A Virus (IAV) infection followed by bacterial pneumonia often leads to hospitalization and death in individuals from high risk groups. Following infection, IAV triggers the process of viral RNA replication which in turn disrupts healthy gut microbial community, while the gut microbiota plays an instrumental role in protecting the host by evolving colonization resistance. Although the underlying mechanisms of IAV infection have been unraveled, the underlying complex mechanisms evolved by gut microbiota in order to induce host immune response following IAV infection remain evasive. In this work, we developed a novel Maximal-Clique based Community Detection algorithm for Weighted undirected Networks (MCCD-WN) and compared its performance with other existing algorithms using three sets of benchmark networks. Moreover, we applied our algorithm to gut microbiome data derived from fecal samples of both healthy and IAV-infected pigs over a sequence of time-points. The results we obtained from the real-life IAV dataset unveil the role of the microbial families Ruminococcaceae, Lachnospiraceae, Spirochaetaceae and Prevotellaceae in the gut microbiome of the IAV-infected cohort. Furthermore, the additional integration of metaproteomic data enabled not only the identification of microbial biomarkers, but also the elucidation of their functional roles in protecting the host following IAV infection. Our network analysis reveals a fast recovery of the infected cohort after the second IAV infection and provides insights into crucial roles of Desulfovibrionaceae and Lactobacillaceae families in combating Influenza A Virus infection. Source code of the community detection algorithm can be downloaded from https://github.com/AniBhar84/MCCD-WN.
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Affiliation(s)
- Anirban Bhar
- Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
| | | | - Alexander Meene
- Institute of Microbiology, University of Greifswald, Greifswald, Germany
| | - Haitao Wang
- Institute of Microbiology, University of Greifswald, Greifswald, Germany
| | - Claudia Karte
- Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany
| | - Theresa Schwaiger
- Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany
| | - Charlotte Schröder
- Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Greifswald, Germany
| | | | - Tim Urich
- Institute of Microbiology, University of Greifswald, Greifswald, Germany
| | - Katharina Riedel
- Institute of Microbiology, University of Greifswald, Greifswald, Germany
| | - Lars Kaderali
- Institute of Bioinformatics, University Medicine Greifswald, Greifswald, Germany
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Velichko A, Huyut MT, Belyaev M, Izotov Y, Korzun D. Machine Learning Sensors for Diagnosis of COVID-19 Disease Using Routine Blood Values for Internet of Things Application. SENSORS (BASEL, SWITZERLAND) 2022; 22:7886. [PMID: 36298235 PMCID: PMC9610709 DOI: 10.3390/s22207886] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/10/2022] [Accepted: 10/14/2022] [Indexed: 05/16/2023]
Abstract
Healthcare digitalization requires effective applications of human sensors, when various parameters of the human body are instantly monitored in everyday life due to the Internet of Things (IoT). In particular, machine learning (ML) sensors for the prompt diagnosis of COVID-19 are an important option for IoT application in healthcare and ambient assisted living (AAL). Determining a COVID-19 infected status with various diagnostic tests and imaging results is costly and time-consuming. This study provides a fast, reliable and cost-effective alternative tool for the diagnosis of COVID-19 based on the routine blood values (RBVs) measured at admission. The dataset of the study consists of a total of 5296 patients with the same number of negative and positive COVID-19 test results and 51 routine blood values. In this study, 13 popular classifier machine learning models and the LogNNet neural network model were exanimated. The most successful classifier model in terms of time and accuracy in the detection of the disease was the histogram-based gradient boosting (HGB) (accuracy: 100%, time: 6.39 sec). The HGB classifier identified the 11 most important features (LDL, cholesterol, HDL-C, MCHC, triglyceride, amylase, UA, LDH, CK-MB, ALP and MCH) to detect the disease with 100% accuracy. In addition, the importance of single, double and triple combinations of these features in the diagnosis of the disease was discussed. We propose to use these 11 features and their binary combinations as important biomarkers for ML sensors in the diagnosis of the disease, supporting edge computing on Arduino and cloud IoT service.
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Affiliation(s)
- Andrei Velichko
- Institute of Physics and Technology, Petrozavodsk State University, 33 Lenin Ave., 185910 Petrozavodsk, Russia
| | - Mehmet Tahir Huyut
- Department of Biostatistics and Medical Informatics, Faculty of Medicine, Erzincan Binali Yıldırım University, 24000 Erzincan, Türkiye
| | - Maksim Belyaev
- Institute of Physics and Technology, Petrozavodsk State University, 33 Lenin Ave., 185910 Petrozavodsk, Russia
| | - Yuriy Izotov
- Institute of Physics and Technology, Petrozavodsk State University, 33 Lenin Ave., 185910 Petrozavodsk, Russia
| | - Dmitry Korzun
- Department of Computer Science, Institute of Mathematics and Information Technology, Petrozavodsk State University, 33 Lenin Ave., 185910 Petrozavodsk, Russia
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Volfovitch Y, Tsur AM, Gurevitch M, Novick D, Rabinowitz R, Mandel M, Achiron A, Rubinstein M, Shoenfeld Y, Amital H. The intercorrelations between blood levels of ferritin, sCD163, and IL-18 in COVID-19 patients and their association to prognosis. Immunol Res 2022; 70:817-828. [PMID: 36222965 PMCID: PMC9555272 DOI: 10.1007/s12026-022-09312-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 08/15/2022] [Indexed: 11/30/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is associated with immune dysregulation, severe respiratory failure, and multiple organ dysfunction caused by a cytokine storm involving high blood levels of ferritin and IL-18. Furthermore, there is a resemblance between COVID-19 and macrophage activation syndrome (MAS) characterized by high concentrations of soluble CD163 (sCD163) receptor and IL-18. High levels of ferritin, IL-18, and sCD163 receptor are associated with “hyperferritinemic syndrome”, a family of diseases that appears to include COVID-19. In this retrospective cohort study, we tested the association and intercorrelations in the serum levels of ferritin, sCD163, and IL-18 and their impact on the prognosis of COVID-19. We analyzed data of 70 hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of sCD163, ferritin, and IL-18 were measured and the correlation of these parameters with the respiratory deterioration and overall 30-day survival was assessed. Among the 70 patients, 60 survived 30 days from hospitalization. There were substantial differences between the subjects who were alive following 30 days compared to those who expired. The differences were referring to lymphocyte and leukocyte count, CRP, D-dimer, ferritin, sCD163, and IL-18. Results showed high levels of IL-18 (median, 444 pg/mL in the survival group compared with 916 pg/mL in the mortality group, p-value 8.54 × 10–2), a statistically significant rise in levels of ferritin (median, 484 ng/mL in the survival group compared with 1004 ng/mL in the mortality group p-value, 7.94 × 10–3), and an elevated value of in sCD163 (mean, 559 ng/mL in the survival group compared with 840 ng/mL in the mortality group, p-value 1.68 × 10–2). There was no significant correlation between the rise of ferritin and the levels sCD163 or IL-18. Taken together, sCD163, ferritin, and IL-18 were found to correlate with the severity of COVID-19 infection. Although these markers are associated with COVID-19 and might contribute to the cytokine storm, no intercorrelation was found among them. It cannot be excluded though that the results depend on the timing of sampling, assuming that they play distinct roles in different stages of the disease course. The data represented herein may provide clinical benefit in improving our understanding of the pathological course of the disease. Furthermore, measuring these biomarkers during the disease progression may help target them at the right time and refine the decision-making regarding the requirement for hospitalization.
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Affiliation(s)
- Yuval Volfovitch
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Avishai M Tsur
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.,The Israel Defense Forces Medical Corps, Ramat Gan, Israel.,Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel
| | - Michael Gurevitch
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Daniela Novick
- Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
| | - Roy Rabinowitz
- Department of Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mathilda Mandel
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Anat Achiron
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Menachem Rubinstein
- Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel
| | - Yehuda Shoenfeld
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.,I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.,Ariel University, Ariel, Israel.,Zabludowicz Center for Autoimmune Diseases, H. Sheba Medical Center, Tel Hashomer, Israel
| | - Howard Amital
- Department of Medicine 'B', Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
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Engin AB, Engin ED, Engin A. Can iron, zinc, copper and selenium status be a prognostic determinant in COVID-19 patients? ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2022; 95:103937. [PMID: 35882309 PMCID: PMC9307469 DOI: 10.1016/j.etap.2022.103937] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/18/2022] [Accepted: 07/21/2022] [Indexed: 05/14/2023]
Abstract
In severe COVID-19, the levels of iron (Fe), copper (Cu), zinc (Zn) and selenium (Se), do not only regulate host immune responses, but modify the viral genome, as well. While low serum Fe concentration is an independent risk factor for the increased death rate, Zn controls oxidative stress, synthesis of inflammatory cytokines and viral replication. Therefore, Zn deficiency associates with a worse prognosis. Although Cu exposure inactivates the viral genome and exhibits spike protein dispersal, increase in Cu/Zn due to high serum Cu levels, are correlated with enhanced risk of infections. Se levels are significantly higher in surviving COVID-19 patients. Meanwhile, both Zn and Se suppress the replication of SARS-CoV-2. Since the balance between the deficiency and oversupply of these metals due to a reciprocal relationship, has decisive effect on the prognosis of the SARS-CoV-2 infection, monitoring their concentrations may facilitate improved outcomes for patients suffering from COVID-19.
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Affiliation(s)
- Ayse Basak Engin
- Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey.
| | - Evren Doruk Engin
- Ankara University, Biotechnology Institute, Gumusdere Campus, Kecioren, Ankara, Turkey
| | - Atilla Engin
- Gazi University, Faculty of Medicine, Department of General Surgery, Ankara, Turkey
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Mohus RM, Flatby H, Liyanarachi KV, DeWan AT, Solligård E, Damås JK, Åsvold BO, Gustad LT, Rogne T. Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study. Sci Rep 2022; 12:16157. [PMID: 36171422 PMCID: PMC9516524 DOI: 10.1038/s41598-022-20679-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/16/2022] [Indexed: 01/15/2023] Open
Abstract
Observational studies have indicated an association between iron status and risk of sepsis and COVID-19. We estimated the effect of genetically-predicted iron biomarkers on risk of sepsis and risk of being hospitalized with COVID-19, performing a two-sample Mendelian randomization study. For risk of sepsis, one standard deviation increase in genetically-predicted serum iron was associated with odds ratio (OR) of 1.14 (95% confidence interval [CI] 1.01-1.29, P = 0.031). The findings were supported in the analyses for transferrin saturation and total iron binding capacity, while the estimate for ferritin was inconclusive. We found a tendency of higher risk of hospitalization with COVID-19 for serum iron; OR 1.29 (CI 0.97-1.72, P = 0.08), whereas sex-stratified analyses showed OR 1.63 (CI 0.94-2.86, P = 0.09) for women and OR 1.21 (CI 0.92-1.62, P = 0.17) for men. Sensitivity analyses supported the main findings and did not suggest bias due to pleiotropy. Our findings suggest a causal effect of genetically-predicted higher iron status and risk of hospitalization due to sepsis and indications of an increased risk of being hospitalized with COVID-19. These findings warrant further studies to assess iron status in relation to severe infections, including the potential of improved management.
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Affiliation(s)
- Randi Marie Mohus
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.52522.320000 0004 0627 3560Clinic of Anesthesia and Intensive Care, St. Olavs Hospital, Trondheim University Hospital, Postboks 3250 Torgarden, 7006 Trondheim, Norway
| | - Helene Flatby
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Kristin V. Liyanarachi
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.52522.320000 0004 0627 3560Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Andrew T. DeWan
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.47100.320000000419368710Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT USA
| | - Erik Solligård
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Jan Kristian Damås
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.52522.320000 0004 0627 3560Department of Infectious Diseases, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway ,grid.5947.f0000 0001 1516 2393Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Bjørn Olav Åsvold
- grid.5947.f0000 0001 1516 2393Department of Public Health and Nursing, K.G. Jebsen Center for Genetic Epidemiology, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.52522.320000 0004 0627 3560Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway ,grid.5947.f0000 0001 1516 2393Department of Public Health and Nursing, HUNT Research Centre, NTNU, Norwegian University of Science and Technology, Levanger, Norway
| | - Lise T. Gustad
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,Nord-Trøndelag Hospital Trust, Levanger, Norway ,grid.465487.cFaculty of Health Sciences, Nord University, Levanger, Norway
| | - Tormod Rogne
- grid.5947.f0000 0001 1516 2393Gemini Center for Sepsis Research, Institute of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway ,grid.47100.320000000419368710Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT USA ,grid.418193.60000 0001 1541 4204Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
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Al-Ani RM. Rhino-orbital-cerebral mucormycosis as a complication of coronavirus disease 2019. World J Virol 2022; 11:293-299. [PMID: 36188746 PMCID: PMC9523325 DOI: 10.5501/wjv.v11.i5.293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 05/13/2022] [Accepted: 08/12/2022] [Indexed: 02/05/2023] Open
Abstract
Coronavirus disease 2019 is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. This disease as well as its various treatments like steroids, antivirals, and antibacterials can alter the immune state of the affected individuals and result in secondary infections such as mucormycosis. Mucormycosis is a well-known opportunistic fungal infection that affects immunocompromised subjects, particularly those with diabetes mellitus, prolonged antibiotic or steroid use, and patients with organ trans-plantation, neutropenia, and hematological malignancies. Rhino-orbital-cerebral mucormycosis is an aggressive disease owing to its ability to invade the blood vessels by fungal hyphae, leading to necrosis of the involved structures. Large cases were reported from India, indicating that this clinical entity shows a geographical variation. The affected patients are suffering on a clinical spectrum depending on the stage of the disease. Radiological assessment, including computerized tomography and magnetic resonance imaging, is necessary to evaluate the stage of the disease and choose the appropriate surgical treatment. A multidisciplinary approach is required to treat rhino-orbital-cerebral mucor-mycosis and includes local or intravenous antifungal drugs, debridement of the dead tissues, and appropriate management of any predisposing conditions. The disease has a very poor prognosis with a death rate of 50%. This review aimed to sum-marize the demographic and clinical risk factors, investigations, treatments, and outcomes of coronavirus disease 2019 patients with rhino-orbital-cerebral mucormycosis.
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Affiliation(s)
- Raid M Al-Ani
- Department of Surgery/Otolaryngology, University of Anbar, College of Medicine, Ramadi 31001, Anbar, Iraq
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Singhal P, Rawat A, Sharma S, Sharma AK, Jat KS, Agarwal S, Samdani S, Agarwal S, Sharma MP, Bhandari S. Invasive Fungal Infections in Dengue Recovered Patients: A New Phenomenon in the Covid-19 Era. Indian J Otolaryngol Head Neck Surg 2022; 74:3321-3326. [PMID: 36090297 PMCID: PMC9441130 DOI: 10.1007/s12070-022-03152-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 08/25/2022] [Indexed: 11/26/2022] Open
Abstract
Invasive fungal rhinosinusitis was seen to rise to epidemic levels after the 2nd wave of ongoing Covid pandemic, especially in tropical countries, maximally in India. A similar trend is being observed for cases who have recently recovered from dengue virus infection. Post dengue invasive fungal infection is a new presentation and any associations between it and Covid pandemic need to be studied in detail to help prepare for any complications. 3 patients presented to the out-patient department of E.N.T at a tertiary level teaching hospital in East India with complains similar to rhinosinusitis. These patients were then evaluated and diagnosed to be infected from Mucormycosis and Aspergillosis fungal sinusitis after which they were managed with surgical debridement and systemic antifungal therapy. All had a recent history of recovery from Dengue virus infection and a possible association could be suspected. 3 patients presented with complains of pain over upper jaw with orbital swelling and loss of vision developing over a period of 24 days. Two of them had ulceration of hard palate. They were then subjected to Contrast MRI along with CT scan of the Paranasal sinuses which depicted pansinus involvement with intracranial extension in two patients. These were then planned for diagnostic nasal endoscopies along with biopsies which turned out to be Invasive fungal sinusitis in the form of Aspergillosis and Mucormycosis. All the 3 patients had recent history of recovery from Dengue virus infection and did not have any other co-morbidities. Covid Associated Mucormycosis (CAM) is a well-known entity now but no reports of Dengue associated Invasive fungal sinusitis are yet reported. Whether this new phenomenon has anything to do with the interactions between dengue virus and coronavirus is not known at present and needs to be studied in detail so appropriate management protocols can be formulated.
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Affiliation(s)
- Pawan Singhal
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Anshu Rawat
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Shivam Sharma
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Anjani Kumar Sharma
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Kailash Singh Jat
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Shubham Agarwal
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Sunil Samdani
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Sunita Agarwal
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Man Prakash Sharma
- Department of Otorhinolaryngology and Head Neck Surgery, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
| | - Sudheer Bhandari
- Department of Internal Medicine, S.M.S Medical College and Hospital, Jaipur, Rajasthan 302004 India
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Kell DB, Pretorius E. The potential role of ischaemia-reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications. Biochem J 2022; 479:1653-1708. [PMID: 36043493 PMCID: PMC9484810 DOI: 10.1042/bcj20220154] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 02/07/2023]
Abstract
Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety of acute circumstances. We argue here that I-R injury also underpins elements of the pathology of a variety of chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be initiated via fibrin amyloid microclot blockage of capillaries, for instance as exercise is started; reperfusion is a necessary corollary when it finishes. We rehearse the mechanistic evidence for these occurrences here, in terms of their manifestation as oxidative stress, hyperinflammation, mast cell activation, the production of marker metabolites and related activities. Such microclot-based phenomena can explain both the breathlessness/fatigue and the post-exertional malaise that may be observed in these conditions, as well as many other observables. The recognition of these processes implies, mechanistically, that therapeutic benefit is potentially to be had from antioxidants, from anti-inflammatories, from iron chelators, and via suitable, safe fibrinolytics, and/or anti-clotting agents. We review the considerable existing evidence that is consistent with this, and with the biochemical mechanisms involved.
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Affiliation(s)
- Douglas B. Kell
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Kemitorvet 200, 2800 Kgs Lyngby, Denmark
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
| | - Etheresia Pretorius
- Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 7ZB, U.K
- Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland 7602, South Africa
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Lin Z, Yang X, Guan L, Qin L, Ding J, Zhou L. The link between ferroptosis and airway inflammatory diseases: A novel target for treatment. Front Mol Biosci 2022; 9:985571. [PMID: 36060261 PMCID: PMC9428508 DOI: 10.3389/fmolb.2022.985571] [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: 07/04/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
Ferroptosis is an iron-dependent mode of cell death characterized by intracellular lipid peroxide accumulation and a redox reaction imbalance. Compared with other modes of cell death, ferroptosis has specific biological and morphological features. The iron-dependent lipid peroxidation accumulation is manifested explicitly in the abnormal metabolism of intracellular lipid oxides catalyzed by excessive iron ions with the production of many reactive oxygen species and over-oxidization of polyunsaturated fatty acids. Recent studies have shown that various diseases, which include intestinal diseases and cancer, are associated with ferroptosis, but few studies are related to airway inflammatory diseases. This review provides a comprehensive analysis of the primary damage mechanisms of ferroptosis and summarizes the relationship between ferroptosis and airway inflammatory diseases. In addition to common acute and chronic airway inflammatory diseases, we also focus on the progress of research on COVID-19 in relation to ferroptosis. New therapeutic approaches and current issues to be addressed in the treatment of inflammatory airway diseases using ferroptosis are further proposed.
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