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Corona A, Simoncini S, Richini G, Gatti I, Santorsola C, Patroni A, Tomasini G, Capone A, Zendra E, Shuman M. Ig-M and Ig-A Enriched Ig-G Infusion as Adjuvant Therapy in the Critically ill Patients Experiencing SARS-CoV-2 Severe Infection. J Intensive Care Med 2025; 40:536-546. [PMID: 39648609 DOI: 10.1177/08850666241301689] [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: 12/10/2024]
Abstract
Introduction: SARS-CoV-2 in patients who need Intensive Care (ICU) is associated with a mortality rate ranging from 10 to 40%-45%, with an increase in morbidity and mortality in presence of sepsis. Methods: We assumed that immunoglobulin (Ig) M and IgA enriched IgG (IGAM) therapy may support SARS COV-2 sepsis-related phase improving patient outcome. We conducted a retrospective case-control study on all the patients admitted to our ICU during the three pandemic waves between February 2020 and April 2021. Upon ICU admission, patients received anticoagulants with the standard supportive treatment (ST) ± IGAM therapy. After matching for the baseline characteristics and treatments, the patients receiving IGAM therapy too (group A), were compared with those undergoing ST (group B) only. Results: 85 patients were enrolled in group A, whereas 111 in group B. The mortality resulted lower in group A [37.6% versus 55.8%, OR: 0.7 (02-08), P = .01)]. A logistic regression analysis identified IGAM treatment as a survival predictor [OR: 0.35 (95%CI, 0.2-0.8)], whereas experiencing a super-infection [OR: 1.88 (95%CI, 1.5-4.9)] and a septic shock [OR: 1.92 (95%CI, 1.4-4.3)] as predictors of death. On day 7, the probability of dying was 3 times higher in patients treated with ST only. Variable life adjustment display (VLAD) was equal to 2.4 in group A, while - 2.2 group B (in terms of lives saved in relation with those expected, in according with Simplified Acute Physiology Score II (SAPS II) score. Conclusion: The treatment based on IGAM infusion seems to give an advantage chance of survival in SARS-CoV-2 severe infection. Further prospective studies are warranted.
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Affiliation(s)
- Alberto Corona
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Sara Simoncini
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Giuseppe Richini
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Ivan Gatti
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Clemente Santorsola
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Andrea Patroni
- Medical Directorate, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Giacomina Tomasini
- ICU, Anaesthesia and Emergency Department, ASST Valcamonica, Esine & Edolo Hospitals, Breno (BS), Italy
| | - Alice Capone
- ICU, Anaesthesia and Emergency Department, ASST Spedali Civili di Brescia, Brescia (BS), Italy
| | - Elena Zendra
- ICU, Anaesthesia and Emergency Department, ASST Spedali Civili di Brescia, Brescia (BS), Italy
| | - Myriam Shuman
- Department of Anaesthesiology, Pain Medicine and Perioperative Care, University of Washington, Seattle, Washington, USA
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Huang Y, Li S, Ye W, Wang H, Su J, Gao L, Shi R, Mou X, Leng SX, Xiao C, Chen G. Viral Infections in Elderly Individuals: A Comprehensive Overview of SARS-CoV-2 and Influenza Susceptibility, Pathogenesis, and Clinical Treatment Strategies. Vaccines (Basel) 2025; 13:431. [PMID: 40333344 PMCID: PMC12031201 DOI: 10.3390/vaccines13040431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2025] [Revised: 04/12/2025] [Accepted: 04/15/2025] [Indexed: 05/09/2025] Open
Abstract
As age increases, the immune function of elderly individuals gradually decreases, increasing their susceptibility to infectious diseases. Therefore, further research on common viral infections in the elderly population, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, is crucial for scientific progress. This review delves into the genetic structure, infection mechanisms, and impact of coinfections with these two viruses and provides a detailed analysis of the reasons for the increased susceptibility of elderly individuals to dual viral infections. We evaluated the clinical manifestations in elderly individuals following coinfections, including complications in the respiratory, gastrointestinal, nervous, and cardiovascular systems. Ultimately, we have summarized the current strategies for the prevention, diagnosis, and treatment of SARS-CoV-2 and influenza coinfections in older adults. Through these studies, we aim to reduce the risk of dual infections in elderly individuals and provide a scientific basis for the prevention, diagnosis, and treatment of age-related viral diseases, thereby improving their health status.
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Affiliation(s)
- Yanhao Huang
- The Sixth Affiliated Hospital of Jinan University (Dongguan Eastern Central Hospital), School of Medicine, Jinan University, Dongguan 523000, China;
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Shumin Li
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Wenjie Ye
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Haoyun Wang
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Jun Su
- First Affiliated Hospital, Jinan University, Guangzhou 510632, China;
| | - Lijuan Gao
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Ruohu Shi
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Xinyi Mou
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Sean Xiao Leng
- Johns Hopkins Center on Aging and Immune Remodeling, Division of Geriatric Medicine and Gerontology, Departments of Medicine, Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD 21205, USA;
| | - Chanchan Xiao
- The Sixth Affiliated Hospital of Jinan University (Dongguan Eastern Central Hospital), School of Medicine, Jinan University, Dongguan 523000, China;
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
- Zhuhai Institute of Jinan University, Jinan University, Zhuhai 519070, China
| | - Guobing Chen
- The Sixth Affiliated Hospital of Jinan University (Dongguan Eastern Central Hospital), School of Medicine, Jinan University, Dongguan 523000, China;
- Department of Microbiology and Immunology, Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou 510632, China; (S.L.); (W.Y.); (H.W.); (L.G.); (R.S.); (X.M.)
- Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
- Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou 510632, China
- Zhuhai Institute of Jinan University, Jinan University, Zhuhai 519070, China
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Michalak KP, Michalak AZ, Brenk-Krakowska A. Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review. Front Immunol 2025; 16:1582783. [PMID: 40313948 PMCID: PMC12043656 DOI: 10.3389/fimmu.2025.1582783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 03/28/2025] [Indexed: 05/03/2025] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recognized not only for its acute effects but also for its ability to cause LongCOVID Syndrome (LCS), a condition characterized by persistent symptoms affecting multiple organ systems. This review examines the molecular and immunological mechanisms underlying LCS, with a particular focus on autophagy inhibition, chronic inflammation, oxidative, nitrosative and calcium stress, viral persistence and autoimmunology. Potential pathophysiological mechanisms involved in LCS include (1) autoimmune activation, (2) latent viral persistence, where SARS-CoV-2 continues to influence host metabolism, (3) reactivation of latent pathogens such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV), exacerbating immune and metabolic dysregulation, and (4) possible persistent metabolic and inflammatory dysregulation, where the body fails to restore post-infection homeostasis. The manipulation of cellular pathways by SARS-CoV-2 proteins is a critical aspect of the virus' ability to evade immune clearance and establish long-term dysfunction. Viral proteins such as NSP13, ORF3a and ORF8 have been shown to disrupt autophagy, thereby impairing viral clearance and promoting immune evasion. In addition, mitochondrial dysfunction, dysregulated calcium signaling, oxidative stress, chronic HIF-1α activation and Nrf2 inhibition create a self-sustaining inflammatory feedback loop that contributes to tissue damage and persistent symptoms. Therefore understanding the molecular basis of LCS is critical for the development of effective therapeutic strategies. Targeting autophagy and Nrf2 activation, glycolysis inhibition, and restoration calcium homeostasis may provide novel strategies to mitigate the long-term consequences of SARS-CoV-2 infection. Future research should focus on personalized therapeutic interventions based on the dominant molecular perturbations in individual patients.
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Affiliation(s)
- Krzysztof Piotr Michalak
- Laboratory of Vision Science and Optometry, Physics and Astronomy Faculty, Adam Mickiewicz University in Poznań, Poznań, Poland
| | | | - Alicja Brenk-Krakowska
- Laboratory of Vision Science and Optometry, Physics and Astronomy Faculty, Adam Mickiewicz University in Poznań, Poznań, Poland
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Gómez-Delgado I, López-Pastor AR, González-Jiménez A, Ramos-Acosta C, Hernández-Garate Y, Martínez-Micaelo N, Amigó N, Espino-Paisán L, Anguita E, Urcelay E. Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19. Cell Biol Toxicol 2025; 41:27. [PMID: 39792183 PMCID: PMC11723900 DOI: 10.1007/s10565-024-09976-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 12/21/2024] [Indexed: 01/12/2025]
Abstract
The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity. The severe groups showed trends to enhanced superoxide production in parallel to lower OPA1-S levels. Unbalance of pivotal mitochondrial fusion (MFN2, OPA1) and fission (DRP1, FIS1) proteins was detected, suggesting a disruption in mitochondrial dynamics, as well as a lack of structural integrity in the electron transport chain. In serum, altered cytokine levels of IL-1β, IFN-α2, and IL-27 persisted long after clinical recovery, and growing amounts of the latter after severe infection correlated with lower basal and maximal respiration, ATP production, and glycolytic capacity. Finally, a trend for higher circulating levels of 3-hydroxybutyrate was found in individuals recovered after severe compared to mild course. In summary, long after acute infection, mitochondrial and metabolic changes seem to differ in a situation of full recovery after mild infection versus the one evolving from severe infection.
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Affiliation(s)
- Irene Gómez-Delgado
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
- Cooperative Research Networks Oriented to Health Results (RICORS, REI), ISCIII, 28029, Madrid, Spain
| | - Andrea R López-Pastor
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
- Cooperative Research Networks Oriented to Health Results (RICORS, REI), ISCIII, 28029, Madrid, Spain
| | - Adela González-Jiménez
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
- Cooperative Research Networks Oriented to Health Results (RICORS, REI), ISCIII, 28029, Madrid, Spain
| | - Carlos Ramos-Acosta
- Hematology Group, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
| | - Yenitzeh Hernández-Garate
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
| | | | - Núria Amigó
- Biosfer Teslab, 43201, Reus, Tarragona, Spain
- Department of Basic Medical Sciences, Rovira I Virgili University, 43007, Tarragona, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Laura Espino-Paisán
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
- Cooperative Research Networks Oriented to Health Results (RICORS, REI), ISCIII, 28029, Madrid, Spain
| | - Eduardo Anguita
- Hematology Group, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain
- Department of Medicine, Medical School, Universidad Complutense de Madrid, 28040, Madrid, Spain
- Hematology Department, IML, Hospital Clínico San Carlos, 28040, Madrid, Spain
| | - Elena Urcelay
- Lab. Genetics and Molecular Bases of Complex Diseases, Health Research Institute of Hospital Clínico San Carlos (IdISSC), 28040, Madrid, Spain.
- Cooperative Research Networks Oriented to Health Results (RICORS, REI), ISCIII, 28029, Madrid, Spain.
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Li J, Pu S, Shu L, Guo M, He Z. Identification of diagnostic candidate genes in COVID-19 patients with sepsis. Immun Inflamm Dis 2024; 12:e70033. [PMID: 39377750 PMCID: PMC11460023 DOI: 10.1002/iid3.70033] [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: 11/23/2023] [Revised: 09/16/2024] [Accepted: 09/19/2024] [Indexed: 10/09/2024] Open
Abstract
PURPOSE Coronavirus Disease 2019 (COVID-19) and sepsis are closely related. This study aims to identify pivotal diagnostic candidate genes in COVID-19 patients with sepsis. PATIENTS AND METHODS We obtained a COVID-19 data set and a sepsis data set from the Gene Expression Omnibus (GEO) database. Identification of differentially expressed genes (DEGs) and module genes using the Linear Models for Microarray Data (LIMMA) and weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, protein-protein interaction (PPI) network construction, and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression and Random Forest (RF)) were used to identify candidate hub genes for the diagnosis of COVID-19 patients with sepsis. Receiver operating characteristic (ROC) curves were developed to assess the diagnostic value. Finally, the data set GSE28750 was used to verify the core genes and analyze the immune infiltration. RESULTS The COVID-19 data set contained 3,438 DEGs， and 595 common genes were screened in sepsis. sepsis DEGs were mainly enriched in immune regulation. The intersection of DEGs for COVID-19 and core genes for sepsis was 329, which were also mainly enriched in the immune system. After developing the PPI network, 17 node genes were filtered and thirteen candidate hub genes were selected for diagnostic value evaluation using machine learning. All thirteen candidate hub genes have diagnostic value, and 8 genes with an Area Under the Curve (AUC) greater than 0.9 were selected as diagnostic genes. CONCLUSION Five core genes (CD3D, IL2RB, KLRC, CD5, and HLA-DQA1) associated with immune infiltration were identified to evaluate their diagnostic utility COVID-19 patients with sepsis. This finding contributes to the identification of potential peripheral blood diagnostic candidate genes for COVID-19 patients with sepsis.
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Affiliation(s)
- Jiuang Li
- Department of Critical Care MedicineThe Third Xiangya Hospital, Central South UniversityChangshaHunanChina
| | - Shiqian Pu
- Department of Critical Care MedicineThe Third Xiangya Hospital, Central South UniversityChangshaHunanChina
| | - Lei Shu
- Department of Critical Care MedicineThe Third Xiangya Hospital, Central South UniversityChangshaHunanChina
| | - Mingjun Guo
- Department of Critical Care MedicineThe Third Xiangya Hospital, Central South UniversityChangshaHunanChina
| | - Zhihui He
- Department of Critical Care MedicineThe Third Xiangya Hospital, Central South UniversityChangshaHunanChina
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Simões JLB, de Carvalho Braga G, Eichler SW, da Silva GB, Bagatini MD. Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration. Purinergic Signal 2024; 20:487-507. [PMID: 38460075 PMCID: PMC11377384 DOI: 10.1007/s11302-024-09998-7] [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: 08/25/2023] [Accepted: 02/21/2024] [Indexed: 03/11/2024] Open
Abstract
The pathophysiology of Parkinson's disease (PD) is marked by degeneration of dopaminergic neurons in the substantia nigra. With advent of COVID-19, which is closely associated with generalized inflammation and multiple organ dysfunctions, the PD patients may develop severe conditions of disease leading to exacerbated degeneration. This condition is caused by the excessive release of pro-inflammatory markers, called cytokine storm, that is capable of triggering neurodegenerative conditions by affecting the blood-brain barrier (BBB). A possible SARS-CoV-2 infection, in serious cases, may compromise the immune system by triggering a hyperstimulation of the neuroimmune response, similar to the pathological processes found in PD. From this perspective, the inflammatory scenario triggers oxidative stress and, consequently, cellular dysfunction in the nervous tissue. The P2X7R seems to be the key mediator of the neuroinflammatory process, as it acts by increasing the concentration of ATP, allowing the influx of Ca2+ and the occurrence of mutations in the α-synuclein protein, causing activation of this receptor. Thus, modulation of the purinergic system may have therapeutic potential on the effects of PD, as well as on the damage caused by inflammation of the BBB, which may be able to mitigate the neurodegeneration caused by diseases. Considering all the processes of neuroinflammation, oxidative stress, and mitochondrial dysfunction that PD propose, we can conclude that the P2X7 antagonist acts in the prevention of viral diseases, and it also controls purinergic receptors formed by multi-target compounds directed to self-amplification circuits and, therefore, may be a viable strategy to obtain the desired disease-modifying effect. Thus, purinergic system receptor modulations have a high therapeutic potential for neurodegenerative diseases such as PD.
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Affiliation(s)
| | | | | | - Gilnei Bruno da Silva
- Multicentric Postgraduate Program in Biochemistry and Molecular Biology, State University of Santa Catarina, Lages, SC, Brazil
| | - Margarete Dulce Bagatini
- Graduate Program in Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, SC, Brazil.
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Jing S, Zhang Y, Zhao W, Li Y, Wen Y. The predictive value of peripheral blood cell mitochondrial gene expression in identifying the prognosis in pediatric sepsis at preschool age. Front Cell Infect Microbiol 2024; 14:1413103. [PMID: 39113822 PMCID: PMC11303305 DOI: 10.3389/fcimb.2024.1413103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 07/08/2024] [Indexed: 08/10/2024] Open
Abstract
Background Sepsis represents a severe manifestation of infection often accompanied by metabolic disorders and mitochondrial dysfunction. Notably, mitochondrial DNA copy number (mtDNA-CN) and the expression of specific mitochondrial genes have emerged as sensitive indicators of mitochondrial function. To investigate the utility of mitochondrial gene expression in peripheral blood cells for distinguishing severe infections and predicting associated outcomes, we conducted a prospective cohort study. Methods We established a prospective cohort comprising 74 patients with non-sepsis pneumonia and 67 cases of sepsis induced by respiratory infections, aging from 2 to 6 years old. We documented corresponding clinical data and laboratory information and collected blood samples upon initial hospital admission. Peripheral blood cells were promptly isolated, and both total DNA and RNA were extracted. We utilized absolute quantification PCR to assess mtDNA-CN, as well as the expression levels of mt-CO1, mt-ND1, and mt-ATP6. Subsequently, we extended these comparisons to include survivors and non-survivors among patients with sepsis using univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic potential. Results The mtDNA-CN in peripheral blood cells was significantly lower in the sepsis group. Univariate analysis revealed a significant reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 in patients with sepsis. However, multivariate analysis did not support the use of mitochondrial function in peripheral blood cells for sepsis diagnosis. In the comparison between pediatric sepsis survivors and non-survivors, univariate analysis indicated a substantial reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 among non-survivors. Notably, total bilirubin (TB), mt-CO1, mt-ND1, and mt-ATP6 levels were identified as independent risk factors for sepsis-induced mortality. ROC curves were then established for these independent risk factors, revealing areas under the curve (AUCs) of 0.753 for TB (95% CI 0.596-0.910), 0.870 for mt-CO1 (95% CI 0.775-0.965), 0.987 for mt-ND1 (95% CI 0.964-1.000), and 0.877 for mt-ATP6 (95% CI 0.793-0.962). Conclusion MtDNA-CN and mitochondrial gene expression are closely linked to the severity and clinical outcomes of infectious diseases. Severe infections lead to impaired mitochondrial function in peripheral blood cells. Notably, when compared to other laboratory parameters, the expression levels of mt-CO1, mt-ND1, and mt-ATP6 demonstrate promising potential for assessing the prognosis of pediatric sepsis.
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Affiliation(s)
- Siyuan Jing
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yue Zhang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wanling Zhao
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yifei Li
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yan Wen
- Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Emergency, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Rurek M. Mitochondria in COVID-19: from cellular and molecular perspective. Front Physiol 2024; 15:1406635. [PMID: 38974521 PMCID: PMC11224649 DOI: 10.3389/fphys.2024.1406635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/27/2024] [Indexed: 07/09/2024] Open
Abstract
The rapid development of the COVID-19 pandemic resulted in a closer analysis of cell functioning during β-coronavirus infection. This review will describe evidence for COVID-19 as a syndrome with a strong, albeit still underestimated, mitochondrial component. Due to the sensitivity of host mitochondria to coronavirus infection, SARS-CoV-2 affects mitochondrial signaling, modulates the immune response, modifies cellular energy metabolism, induces apoptosis and ageing, worsening COVID-19 symptoms which can sometimes be fatal. Various aberrations across human systems and tissues and their relationships with mitochondria were reported. In this review, particular attention is given to characterization of multiple alterations in gene expression pattern and mitochondrial metabolism in COVID-19; the complexity of interactions between SARS-CoV-2 and mitochondrial proteins is presented. The participation of mitogenome fragments in cell signaling and the occurrence of SARS-CoV-2 subgenomic RNA within membranous compartments, including mitochondria is widely discussed. As SARS-CoV-2 severely affects the quality system of mitochondria, the cellular background for aberrations in mitochondrial dynamics in COVID-19 is additionally characterized. Finally, perspectives on the mitigation of COVID-19 symptoms by affecting mitochondrial biogenesis by numerous compounds and therapeutic treatments are briefly outlined.
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Affiliation(s)
- Michał Rurek
- Department of Molecular and Cellular Biology, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznań, Poland
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9
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Piel S, McManus MJ, Heye KN, Beaulieu F, Fazelinia H, Janowska JI, MacTurk B, Starr J, Gaudio H, Patel N, Hefti MM, Smalley ME, Hook JN, Kohli NV, Bruton J, Hallowell T, Delso N, Roberts A, Lin Y, Ehinger JK, Karlsson M, Berg RA, Morgan RW, Kilbaugh TJ. Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest. Sci Rep 2024; 14:13852. [PMID: 38879681 PMCID: PMC11180202 DOI: 10.1038/s41598-024-64317-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 06/07/2024] [Indexed: 06/19/2024] Open
Abstract
Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF's protective mechanisms and optimize its therapeutic application in post-arrest care.
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Affiliation(s)
- Sarah Piel
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA.
- Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
- CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty of the Heinrich-Heine-University, Düsseldorf, Germany.
| | - Meagan J McManus
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Kristina N Heye
- Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Forrest Beaulieu
- Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Hossein Fazelinia
- Proteomics Core Facility, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Joanna I Janowska
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Bryce MacTurk
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Jonathan Starr
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Hunter Gaudio
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Nisha Patel
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Marco M Hefti
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Martin E Smalley
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Jordan N Hook
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
| | - Neha V Kohli
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - James Bruton
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Thomas Hallowell
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Nile Delso
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Anna Roberts
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Yuxi Lin
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Johannes K Ehinger
- Mitochondrial Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Otorhinolaryngology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
- Otorhinolaryngology, Head and Neck Surgery, Skåne University Hospital, Lund, Sweden
| | | | - Robert A Berg
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Ryan W Morgan
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
| | - Todd J Kilbaugh
- Resuscitation Science Center of Emphasis, The Children's Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, PA, 19104, USA
- Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA
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10
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Naidu AS, Wang CK, Rao P, Mancini F, Clemens RA, Wirakartakusumah A, Chiu HF, Yen CH, Porretta S, Mathai I, Naidu SAG. Precision nutrition to reset virus-induced human metabolic reprogramming and dysregulation (HMRD) in long-COVID. NPJ Sci Food 2024; 8:19. [PMID: 38555403 PMCID: PMC10981760 DOI: 10.1038/s41538-024-00261-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 03/15/2024] [Indexed: 04/02/2024] Open
Abstract
SARS-CoV-2, the etiological agent of COVID-19, is devoid of any metabolic capacity; therefore, it is critical for the viral pathogen to hijack host cellular metabolic machinery for its replication and propagation. This single-stranded RNA virus with a 29.9 kb genome encodes 14 open reading frames (ORFs) and initiates a plethora of virus-host protein-protein interactions in the human body. These extensive viral protein interactions with host-specific cellular targets could trigger severe human metabolic reprogramming/dysregulation (HMRD), a rewiring of sugar-, amino acid-, lipid-, and nucleotide-metabolism(s), as well as altered or impaired bioenergetics, immune dysfunction, and redox imbalance in the body. In the infectious process, the viral pathogen hijacks two major human receptors, angiotensin-converting enzyme (ACE)-2 and/or neuropilin (NRP)-1, for initial adhesion to cell surface; then utilizes two major host proteases, TMPRSS2 and/or furin, to gain cellular entry; and finally employs an endosomal enzyme, cathepsin L (CTSL) for fusogenic release of its viral genome. The virus-induced HMRD results in 5 possible infectious outcomes: asymptomatic, mild, moderate, severe to fatal episodes; while the symptomatic acute COVID-19 condition could manifest into 3 clinical phases: (i) hypoxia and hypoxemia (Warburg effect), (ii) hyperferritinemia ('cytokine storm'), and (iii) thrombocytosis (coagulopathy). The mean incubation period for COVID-19 onset was estimated to be 5.1 days, and most cases develop symptoms after 14 days. The mean viral clearance times were 24, 30, and 39 days for acute, severe, and ICU-admitted COVID-19 patients, respectively. However, about 25-70% of virus-free COVID-19 survivors continue to sustain virus-induced HMRD and exhibit a wide range of symptoms that are persistent, exacerbated, or new 'onset' clinical incidents, collectively termed as post-acute sequelae of COVID-19 (PASC) or long COVID. PASC patients experience several debilitating clinical condition(s) with >200 different and overlapping symptoms that may last for weeks to months. Chronic PASC is a cumulative outcome of at least 10 different HMRD-related pathophysiological mechanisms involving both virus-derived virulence factors and a multitude of innate host responses. Based on HMRD and virus-free clinical impairments of different human organs/systems, PASC patients can be categorized into 4 different clusters or sub-phenotypes: sub-phenotype-1 (33.8%) with cardiac and renal manifestations; sub-phenotype-2 (32.8%) with respiratory, sleep and anxiety disorders; sub-phenotype-3 (23.4%) with skeleto-muscular and nervous disorders; and sub-phenotype-4 (10.1%) with digestive and pulmonary dysfunctions. This narrative review elucidates the effects of viral hijack on host cellular machinery during SARS-CoV-2 infection, ensuing detrimental effect(s) of virus-induced HMRD on human metabolism, consequential symptomatic clinical implications, and damage to multiple organ systems; as well as chronic pathophysiological sequelae in virus-free PASC patients. We have also provided a few evidence-based, human randomized controlled trial (RCT)-tested, precision nutrients to reset HMRD for health recovery of PASC patients.
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Affiliation(s)
- A Satyanarayan Naidu
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA.
- N-terminus Research Laboratory, 232659 Via del Rio, Yorba Linda, CA, 92887, USA.
| | - Chin-Kun Wang
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- School of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung, 40201, Taiwan
| | - Pingfan Rao
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- College of Food and Bioengineering, Fujian Polytechnic Normal University, No.1, Campus New Village, Longjiang Street, Fuqing City, Fujian, China
| | - Fabrizio Mancini
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- President-Emeritus, Parker University, 2540 Walnut Hill Lane, Dallas, TX, 75229, USA
| | - Roger A Clemens
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- University of Southern California, Alfred E. Mann School of Pharmacy/D. K. Kim International Center for Regulatory & Quality Sciences, 1540 Alcazar St., CHP 140, Los Angeles, CA, 90089, USA
| | - Aman Wirakartakusumah
- International Union of Food Science and Technology (IUFoST), Guelph, ON, Canada
- IPMI International Business School Jakarta; South East Asian Food and Agriculture Science and Technology, IPB University, Bogor, Indonesia
| | - Hui-Fang Chiu
- Department of Chinese Medicine, Taichung Hospital, Ministry of Health & Well-being, Taichung, Taiwan
| | - Chi-Hua Yen
- Department of Family and Community Medicine, Chung Shan Medical University Hospital; School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Sebastiano Porretta
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- President, Italian Association of Food Technology (AITA), Milan, Italy
- Experimental Station for the Food Preserving Industry, Department of Consumer Science, Viale Tanara 31/a, I-43121, Parma, Italy
| | - Issac Mathai
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- Soukya International Holistic Health Center, Whitefield, Bengaluru, India
| | - Sreus A G Naidu
- Global Nutrition Healthcare Council (GNHC) Mission-COVID, Yorba Linda, CA, USA
- N-terminus Research Laboratory, 232659 Via del Rio, Yorba Linda, CA, 92887, USA
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11
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Ahmad A, Kanmani P, Hu G. Quantitative assessment of mitochondrial membrane potential in macrophages in sepsis. Methods Cell Biol 2024; 194:43-58. [PMID: 40058961 DOI: 10.1016/bs.mcb.2024.01.004] [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: 05/13/2025]
Abstract
Sepsis, a life-threatening condition characterized by dysregulated host response to infection, poses a significant public healthcare challenge. Excessive inflammatory responses during sepsis can lead to mitochondrial dysfunctions, resulting in organ damage. One hallmark of mitochondrial dysfunction is the reduction of mitochondrial membrane potential, which disrupts cellular metabolism, bioenergetics, and decreases the production of high-energy ATP through oxidative phosphorylation. In human sepsis, the mitochondrial membrane potential in peripheral blood monocytes has been identified as a marker of disease severity. Here, we present a detailed and widely accepted protocol for the detection of mitochondrial membrane potential using the JC-1 fluorescent dye in murine bone marrow-derived macrophages and J774A.1 macrophages following stimulation with lipopolysaccharides. This protocol is routinely employed and can be easily adapted for various cell types, intact tissues, and isolated mitochondria with minimal modifications. By utilizing this technique, researchers can gain valuable insights into mitochondrial function in different experimental contexts, potentially advancing our understanding of the pathogenesis and treatment of sepsis-related mitochondrial dysfunction.
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Affiliation(s)
- Ajaz Ahmad
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL, United States
| | - Paulraj Kanmani
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL, United States
| | - Guochang Hu
- Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL, United States; Department of Pharmacology & Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL, United States.
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12
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Heil M. Self-DNA driven inflammation in COVID-19 and after mRNA-based vaccination: lessons for non-COVID-19 pathologies. Front Immunol 2024; 14:1259879. [PMID: 38439942 PMCID: PMC10910434 DOI: 10.3389/fimmu.2023.1259879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 12/26/2023] [Indexed: 03/06/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented concentration of economic and research efforts to generate knowledge at unequalled speed on deregulated interferon type I signalling and nuclear factor kappa light chain enhancer in B-cells (NF-κB)-driven interleukin (IL)-1β, IL-6, IL-18 secretion causing cytokine storms. The translation of the knowledge on how the resulting systemic inflammation can lead to life-threatening complications into novel treatments and vaccine technologies is underway. Nevertheless, previously existing knowledge on the role of cytoplasmatic or circulating self-DNA as a pro-inflammatory damage-associated molecular pattern (DAMP) was largely ignored. Pathologies reported 'de novo' for patients infected with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 to be outcomes of self-DNA-driven inflammation in fact had been linked earlier to self-DNA in different contexts, e.g., the infection with Human Immunodeficiency Virus (HIV)-1, sterile inflammation, and autoimmune diseases. I highlight particularly how synergies with other DAMPs can render immunogenic properties to normally non-immunogenic extracellular self-DNA, and I discuss the shared features of the gp41 unit of the HIV-1 envelope protein and the SARS-CoV 2 Spike protein that enable HIV-1 and SARS-CoV-2 to interact with cell or nuclear membranes, trigger syncytia formation, inflict damage to their host's DNA, and trigger inflammation - likely for their own benefit. These similarities motivate speculations that similar mechanisms to those driven by gp41 can explain how inflammatory self-DNA contributes to some of most frequent adverse events after vaccination with the BNT162b2 mRNA (Pfizer/BioNTech) or the mRNA-1273 (Moderna) vaccine, i.e., myocarditis, herpes zoster, rheumatoid arthritis, autoimmune nephritis or hepatitis, new-onset systemic lupus erythematosus, and flare-ups of psoriasis or lupus. The hope is to motivate a wider application of the lessons learned from the experiences with COVID-19 and the new mRNA vaccines to combat future non-COVID-19 diseases.
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Affiliation(s)
- Martin Heil
- Departamento de Ingeniería Genética, Laboratorio de Ecología de Plantas, Centro de Investigación y de Estudios Avanzados (CINVESTAV)-Unidad Irapuato, Irapuato, Mexico
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13
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Casoli T, Bonfigli AR, Di Rosa M, Giorgetti B, Balietti M, Giacconi R, Cardelli M, Piacenza F, Marchegiani F, Marcheselli F, Recchioni R, Galeazzi R, Vaiasicca S, Lamedica AM, Fumagalli A, Ferrara L, Lattanzio F. Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients. Aging Dis 2024; 15:2665-2681. [PMID: 38377022 PMCID: PMC11567249 DOI: 10.14336/ad.2023.1123] [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: 09/16/2023] [Accepted: 11/23/2023] [Indexed: 02/22/2024] Open
Abstract
COVID-19 remains a serious concern for elderly individuals with underlying comorbidities. SARS-CoV-2 can target and damage mitochondria, potentially leading to mutations in mitochondrial DNA (mtDNA). This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls without COVID-19 (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA variants (40-60% heteroplasmy) and allows the assessment of low-level heteroplasmy (<10% heteroplasmy). Serum concentrations of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic variants in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic variant burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α. These findings suggest that SARS-CoV-2 may induce mtDNA mutations that are related to the degree of inflammation.
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Affiliation(s)
- Tiziana Casoli
- Center for Neurobiology of Aging, IRCCS INRCA, Ancona, Italy.
| | | | - Mirko Di Rosa
- Centre for Biostatistics and Applied Geriatric Clinical Epidemiology, IRCCS INRCA, Ancona, Italy.
| | | | - Marta Balietti
- Center for Neurobiology of Aging, IRCCS INRCA, Ancona, Italy.
| | - Robertina Giacconi
- Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.
| | - Maurizio Cardelli
- Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.
| | - Francesco Piacenza
- Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy.
| | | | | | - Rina Recchioni
- Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy.
| | - Roberta Galeazzi
- Clinic of Laboratory and Precision Medicine, IRCCS INRCA, Ancona, Italy.
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14
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Dellino M, Cerbone M, Fortunato F, Capursi T, Lepera A, Mancini T, Laganà AS, Malvasi A, Trerotoli P, Cormio G, Cicinelli E, Cazzato G, Carriero C, Pinto V, Cascardi E, Vitagliano A. Incidence of pre-neoplastic and neoplastic lesions of the cervix before and after the COVID-19 pandemic. Int J Gynecol Cancer 2024; 34:224-228. [PMID: 38103892 DOI: 10.1136/ijgc-2023-004743] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 11/22/2023] [Indexed: 12/19/2023] Open
Abstract
OBJECTIVE The COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial neoplasia (CIN)2 and CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix before and after the COVID-19 pandemic. METHODS A retrospective analysis was performed using archive data from the Policlinico di Bari, Unit of Gynecology and Obstetrics. The study included patients who tested positive for high-risk human papillomavirus (HPV) at the level I screening test (HPV test) and were subsequently referred to level II screening, which involves the Papanicolaou (Pap) test and colposcopic examination. We excluded individuals who did not comply with the recommended follow-up, patients with low-risk HPV infection, those with autoimmune diseases, oncologic diseases, or those undergoing immunosuppressive therapies. The time period spanned from January 2020 to December 2022. The incidence of CIN2/CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix was compared between the pre-screening period (2017-2019) and the post-screening period (2020-2022). RESULTS The study comprised a cohort of 1558 consecutive European sexually active women with a median age of 34 years (range 25-65) who underwent colposcopic evaluation of the uterine cervix as a level II screening program. The comparison between the pre-screening and post-screening periods showed an increase in the incidence of CIN2/CIN3 lesions, rising from 23.9 to 63.3 per 100 000 (HR 2.62, 95% CI 1.64 to 4.20; p<0.001). Additionally, although there was an absolute increase in the incidence of cervical carcinoma and adenocarcinoma, the comparison did not reach statistical significance (squamous carcinoma: 2017-2019, 2.5 per 100 000; 2020-2022 3.4 per 100 000, p=0.72; adenocarcinoma: 2017-2019, 3.5 per 100 000; 2020-2022 7.6 per 100 000, p=0.24). CONCLUSION This study showed a significant increase in the incidence rate of CIN2/CIN3 lesions after the COVID-19 pandemic. Our findings may be attributed to the temporary suspension of follow-up programs during the pandemic, although the study does not rule out direct effects of SARS-CoV-2 on the risk of pre-neoplastic and neoplastic conditions of the cervix.
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Affiliation(s)
- Miriam Dellino
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Marco Cerbone
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Francesca Fortunato
- Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Teresa Capursi
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Achiropita Lepera
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Tiziana Mancini
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Antonio Simone Laganà
- Unit of Obstetrics and Gynecology, "Paolo Giaccone" Hospital, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Antonio Malvasi
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Paolo Trerotoli
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Gennaro Cormio
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
- Department of Gynecology, University of Bari, Bari, Puglia, Italy
| | - Ettore Cicinelli
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Gerardo Cazzato
- Section of Molecular Pathology, Department of Precision and Regenerative Medicine and IonianArea (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy, Bari, Puglia, Italy
| | - Carmine Carriero
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Vincenzo Pinto
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
| | - Eliano Cascardi
- Section of Molecular Pathology, Department of Precision and Regenerative Medicine and IonianArea (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy, Bari, Puglia, Italy
| | - Amerigo Vitagliano
- Department of Interdisciplinary Medicine (DIM), University of Bari Aldo Moro, Bari, Puglia, Italy
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15
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Karabekmez ME, Yarıcı M. Parameterization of asymmetric sigmoid functions in weighted gene co-expression network analysis. Comput Biol Chem 2024; 108:107998. [PMID: 38071762 DOI: 10.1016/j.compbiolchem.2023.107998] [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: 02/22/2023] [Revised: 11/22/2023] [Accepted: 12/03/2023] [Indexed: 01/22/2024]
Abstract
In most the biological contexts, examining gene expressions at the genomic level gives more accurate results than examining genes individually. It can improve understanding of the molecular mechanisms that cause molecular alterations. Weighted gene co-expression network analysis (WGCNA), which has recently been widely used to cluster transcriptomic datasets, implements a soft thresholding procedure using power function. However, these functions may sometimes exaggerate minor differences in expression correlations. We have previously proposed to use asymmetric sigmoid functions in soft thresholding as an alternative solution. However, the number of variables in asymmetric sigmoid functions may vary and parameterization can be problematic. In this study, we have introduced a systematic procedure for parameterizing asymmetric sigmoid function to ease using it as an alternative soft-thresholding solution in WGCNA. The efficiency of the employment was shown on four different COVID-19 datasets, on a yeast dataset, and on an E.Coli dataset. The results indicate that this approach provides biologically plausible associations for the resulting modules.
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Affiliation(s)
| | - Merve Yarıcı
- Istanbul Medeniyet University, Department of Bioengineering, Istanbul, Turkey
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16
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Chu Y, Li M, Sun M, Wang J, Xin W, Xu L. Gene crosstalk between COVID-19 and preeclampsia revealed by blood transcriptome analysis. Front Immunol 2024; 14:1243450. [PMID: 38259479 PMCID: PMC10800816 DOI: 10.3389/fimmu.2023.1243450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 12/14/2023] [Indexed: 01/24/2024] Open
Abstract
Background The extensive spread of coronavirus disease 2019 (COVID-19) has led to a rapid increase in global mortality. Preeclampsia is a commonly observed pregnancy ailment characterized by high maternal morbidity and mortality rates, in addition to the restriction of fetal growth within the uterine environment. Pregnant individuals afflicted with vascular disorders, including preeclampsia, exhibit an increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection via mechanisms that have not been fully delineated. Additionally, the intricate molecular mechanisms underlying preeclampsia and COVID-19 have not been fully elucidated. This study aimed to discern commonalities in gene expression, regulators, and pathways shared between COVID-19 and preeclampsia. The objective was to uncover potential insights that could contribute to novel treatment strategies for both COVID-19 and preeclampsia. Method Transcriptomic datasets for COVID-19 peripheral blood (GSE152418) and preeclampsia blood (GSE48424) were initially sourced from the Gene Expression Omnibus (GEO) database. Subsequent to that, we conducted a subanalysis by selecting females from the GSE152418 dataset and employed the "Deseq2" package to identify genes that exhibited differential expression. Simultaneously, the "limma" package was applied to identify differentially expressed genes (DEGs) in the preeclampsia dataset (GSE48424). Following that, an intersection analysis was conducted to identify the common DEGs obtained from both the COVID-19 and preeclampsia datasets. The identified shared DEGs were subsequently utilized for functional enrichment analysis, transcription factor (TF) and microRNAs (miRNA) prediction, pathway analysis, and identification of potential candidate drugs. Finally, to validate the bioinformatics findings, we collected peripheral blood mononuclear cell (PBMC) samples from healthy individuals, COVID-19 patients, and Preeclampsia patients. The abundance of the top 10 Hub genes in both diseases was assessed using real-time quantitative polymerase chain reaction (RT-qPCR). Result A total of 355 overlapping DEGs were identified in both preeclampsia and COVID-19 datasets. Subsequent ontological analysis, encompassing Gene Ontology (GO) functional assessment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, revealed a significant association between the two conditions. Protein-protein interactions (PPIs) were constructed using the STRING database. Additionally, the top 10 hub genes (MRPL11, MRPS12, UQCRH, ATP5I, UQCRQ, ATP5D, COX6B1, ATP5O, ATP5H, NDUFA6) were selected based on their ranking scores using the degree algorithm, which considered the shared DEGs. Moreover, transcription factor-gene interactions, protein-drug interactions, co-regulatory networks of DEGs and miRNAs, and protein-drug interactions involving the shared DEGs were also identified in the datasets. Finally, RT-PCR results confirmed that 10 hub genes do exhibit distinct expression profiles in the two diseases. Conclusion This study successfully identified overlapping DEGs, functional pathways, and regulatory elements between COVID-19 and preeclampsia. The findings provide valuable insights into the shared molecular mechanisms and potential therapeutic targets for both diseases. The validation through RT-qPCR further supports the distinct expression profiles of the identified hub genes in COVID-19 and preeclampsia, emphasizing their potential roles as biomarkers or therapeutic targets in these conditions.
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Affiliation(s)
| | | | | | | | | | - Lin Xu
- Department of Obstetrics, the Affiliated Hospital of Qingdao University, Qingdao, China
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17
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Wang D, Zhao H, Deng C, Lei W, Ren J, Zhang S, Yang W, Lu C, Tian Y, Chen Y, Qiu Y, Meng L, Yang Y. Sulfide-modified nanoscale zero-valent iron as a novel therapeutic remedy for septic myocardial injury. J Adv Res 2024; 55:145-158. [PMID: 36801383 PMCID: PMC10770114 DOI: 10.1016/j.jare.2023.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 01/30/2023] [Accepted: 02/12/2023] [Indexed: 02/18/2023] Open
Abstract
INTRODUCTION Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. OBJECTIVES To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. METHODS We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. RESULTS The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. CONCLUSIONS The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.
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Affiliation(s)
- Daquan Wang
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; School of Chemistry, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, 710049, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Huadong Zhao
- Department of General Surgery, Tangdu Hospital, The Airforce Medical University, 1 Xinsi Road, Xi'an, 710038, China
| | - Chao Deng
- Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Wangrui Lei
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Jun Ren
- Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA
| | - Shaofei Zhang
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Wenwen Yang
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Chenxi Lu
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Ye Tian
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China
| | - Ying Chen
- Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China
| | - Yao Qiu
- School of Chemistry, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, 710049, Xi'an, China
| | - Lingjie Meng
- School of Chemistry, MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Jiaotong University, 710049, Xi'an, China.
| | - Yang Yang
- Deparment of Neurology, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University. Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, 710069, China.
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18
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Xiao S, Yuan Z, Huang Y. The Potential Role of Nitric Oxide as a Therapeutic Agent against SARS-CoV-2 Infection. Int J Mol Sci 2023; 24:17162. [PMID: 38138990 PMCID: PMC10742813 DOI: 10.3390/ijms242417162] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/28/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the greatest worldwide public health threat of this century, which may predispose multi-organ failure (especially the lung) and death despite numerous mild and moderate symptoms. Recent studies have unraveled the molecular and clinical characteristics of the infectivity, pathogenicity, and immune evasion of SARS-CoV-2 and thus improved the development of many different therapeutic strategies to combat COVID-19, including treatment and prevention. Previous studies have indicated that nitric oxide (NO) is an antimicrobial and anti-inflammatory molecule with key roles in pulmonary vascular function in the context of viral infections and other pulmonary disease states. This review summarized the recent advances of the pathogenesis of SARS-CoV-2, and accordingly elaborated on the potential application of NO in the management of patients with COVID-19 through antiviral activities and anti-inflammatory properties, which mitigate the propagation of this disease. Although there are some limits of NO in the treatment of COVID-19, it might be a worthy candidate in the multiple stages of COVID-19 prevention or therapy.
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Affiliation(s)
| | | | - Yi Huang
- National Biosafety Laboratory, Chinese Academy of Sciences, Wuhan 430020, China
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19
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Yossadania A, Hayati Z, Harapan H, Saputra I, Mudatsir, Diah M, Ramadhana IF. Quantity of antibiotic use and its association with clinical outcomes in COVID-19 patients: A snapshot from a provincial referral hospital in Indonesia. NARRA J 2023; 3:e272. [PMID: 38450336 PMCID: PMC10914064 DOI: 10.52225/narra.v3i3.272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 12/25/2023] [Indexed: 03/08/2024]
Abstract
Irrational antibiotic use in Indonesia is considered high, yet there are still lacks reliable information regarding the issue. The quantity of antibiotic use studies, in particular during coronavirus disease 2019 (COVID-19) pandemic, was not well reported. The aim of this study was to evaluate antibiotic use in COVID-19 patients at a province referral hospital in Aceh, Indonesia, Dr Zainoel Abidin Hospital, and to assess the association between antibiotic use and COVID-19 clinical outcomes. The defined daily dose (DDD) method was used and expressed in DDDs per 100 patient-days as in hospital setting. The data were obtained from inpatient confirmed COVID-19 patients between March 2020 and December 2021. A logistic regression was used to determine the association between patients' characteristics and antibiotic usage with clinical outcomes. A total of 361 treated COVID-19 patients were included using a random sampling technique and analyzed. Out of 361 patients, 89.2% of them were treated with antibiotic(s). All the antibiotics were given empirically except for cefazoline (5.5%) that was used as prophylaxis to obstetric patients who underwent the c-section. Azithromycin was the most prescribed antibiotic and levofloxacin had the highest DDD. Our data suggested that there was no association between antibiotic use and clinical outcomes of COVID-19 patients (p=0.128). Having sepsis and another pulmonary disease however were associated with mortality of COVID-19 patients with adjusted odds ratio (aOR) 14.14; 95%CI 2.94-67.90, p=0.001 and aOR 8.64; 95%CI 3.30-22.63, p<0.001, respectively. In addition, patients older than 60-year-old had a higher chance to an unfavorable outcome compared to those younger than 30-year-old, aOR: 7.61; 95%CI: 1.07-53.94. In conclusion, the use of antibiotics is prevalent among COVID-19 and it is not directly associated with clinical outcomes.
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Affiliation(s)
- Asyriva Yossadania
- Departement of Public Health, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Zinatul Hayati
- Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Prevention and Control Antimicrobial Resistance Committee, Dr Zainoel Abidin Hospital, Banda Aceh, Indonesia
| | - Harapan Harapan
- Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Tropical Disease Center, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
- Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Indonesia
- Tsunami & Disaster Mitigation Research Centre (TDMRC), Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Irwan Saputra
- Departement of Public Health, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Mudatsir
- Department of Microbiology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Muhammad Diah
- Department of Internal Medicine, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia
| | - Ika F. Ramadhana
- Prevention and Control Antimicrobial Resistance Committee, Dr Zainoel Abidin Hospital, Banda Aceh, Indonesia
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20
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Hanson BA, Visvabharathy L, Orban ZS, Jimenez M, Batra A, Liotta EM, DeLisle RK, Klausner JD, Cohen P, Padhye AS, Tachas G, Koralnik IJ. Plasma proteomics show altered inflammatory and mitochondrial proteins in patients with neurologic symptoms of post-acute sequelae of SARS-CoV-2 infection. Brain Behav Immun 2023; 114:462-474. [PMID: 37704012 PMCID: PMC10718560 DOI: 10.1016/j.bbi.2023.08.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Revised: 07/17/2023] [Accepted: 08/26/2023] [Indexed: 09/15/2023] Open
Abstract
Persistent symptoms of COVID-19 survivors constitute long COVID syndrome, also called post-acute sequelae of SARS-CoV-2 infection (PASC). Neurologic manifestations of PASC (Neuro-PASC) are particularly debilitating, long lasting, and poorly understood. To gain insight into the pathogenesis of PASC, we leveraged a well-characterized group of Neuro-PASC (NP) patients seen at our Neuro-COVID-19 clinic who had mild acute COVID-19 and never required hospitalization to investigate their plasma proteome. Using the SomaLogic platform, SomaScan, the plasma concentration of >7000 proteins was measured from 92 unvaccinated individuals, including 48 NP patients, 20 COVID-19 convalescents (CC) without lingering symptoms, and 24 unexposed healthy controls (HC) to interrogate underlying pathobiology and potential biomarkers of PASC. We analyzed the plasma proteome based on post-COVID-19 status, neurologic and non-neurologic symptoms, as well as subjective and objective standardized tests for changes in quality-of-life (QoL) and cognition associated with Neuro-PASC. The plasma proteome of NP patients differed from CC and HC subjects more substantially than post-COVID-19 groups (NP and CC combined) differed from HC. Proteomic differences in NP patients 3-9 months following acute COVID-19 showed alterations in inflammatory proteins and pathways relative to CC and HC subjects. Proteomic associations with Neuro-PASC symptoms of brain fog and fatigue included changes in markers of DNA repair, oxidative stress, and neutrophil degranulation. Furthermore, we discovered a correlation between NP patients lower subjective impression of recovery to pre-COVID-19 baseline with an increase in the concentration of the oxidative phosphorylation protein COX7A1, which was also associated with neurologic symptoms and fatigue, as well as impairment in QoL and cognitive dysfunction. Finally, we identified other oxidative phosphorylation-associated proteins correlating with central nervous system symptoms. Our results suggest ongoing inflammatory changes and mitochondrial involvement in Neuro-PASC and pave the way for biomarker validation for use in monitoring and development of therapeutic intervention for this debilitating condition.
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Affiliation(s)
- Barbara A Hanson
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Lavanya Visvabharathy
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Zachary S Orban
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Millenia Jimenez
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Ayush Batra
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Eric M Liotta
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | | | - Jeffrey D Klausner
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
| | - Pinchas Cohen
- The Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
| | | | - George Tachas
- Antisense Therapeutics Limited, Toorak, Victoria, Australia
| | - Igor J Koralnik
- Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
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21
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Shoraka S, Samarasinghe AE, Ghaemi A, Mohebbi SR. Host mitochondria: more than an organelle in SARS-CoV-2 infection. Front Cell Infect Microbiol 2023; 13:1228275. [PMID: 37692170 PMCID: PMC10485703 DOI: 10.3389/fcimb.2023.1228275] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Since December 2019, the world has been facing viral pandemic called COVID-19 (Coronavirus disease 2019) caused by a new beta-coronavirus named severe acute respiratory syndrome coronavirus-2, or SARS-CoV-2. COVID-19 patients may present with a wide range of symptoms, from asymptomatic to requiring intensive care support. The severe form of COVID-19 is often marked by an altered immune response and cytokine storm. Advanced age, age-related and underlying diseases, including metabolic syndromes, appear to contribute to increased COVID-19 severity and mortality suggesting a role for mitochondria in disease pathogenesis. Furthermore, since the immune system is associated with mitochondria and its damage-related molecular patterns (mtDAMPs), the host mitochondrial system may play an important role during viral infections. Viruses have evolved to modulate the immune system and mitochondrial function for survival and proliferation, which in turn could lead to cellular stress and contribute to disease progression. Recent studies have focused on the possible roles of mitochondria in SARS-CoV-2 infection. It has been suggested that mitochondrial hijacking by SARS-CoV-2 could be a key factor in COVID-19 pathogenesis. In this review, we discuss the roles of mitochondria in viral infections including SARS-CoV-2 infection based on past and present knowledge. Paying attention to the role of mitochondria in SARS-CoV-2 infection will help to better understand the pathophysiology of COVID-19 and to achieve effective methods of prevention, diagnosis, and treatment.
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Affiliation(s)
- Shahrzad Shoraka
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Amali E. Samarasinghe
- Division of Pulmonology, Allergy and Immunology, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Children’s Foundation Research Institute, Memphis, TN, United States
| | - Amir Ghaemi
- Department of Virology, Pasteur Institute of Iran, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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22
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Li D, Zhao B, Zhuang P, Mei X. Development of nanozymes for promising alleviation of COVID-19-associated arthritis. Biomater Sci 2023; 11:5781-5796. [PMID: 37475700 DOI: 10.1039/d3bm00095h] [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: 07/22/2023]
Abstract
The COVID-19 pandemic caused by SARS-CoV-2 has been identified as a culprit in the development of a variety of disorders, including arthritis. Although the emergence of arthritis following SARS-CoV-2 infection may not be immediately discernible, its underlying pathogenesis is likely to involve a complex interplay of infections, oxidative stress, immune responses, abnormal production of inflammatory factors, cellular destruction, etc. Fortunately, recent advancements in nanozymes with enzyme-like activities have shown potent antiviral effects and the ability to inhibit oxidative stress and cytokines and provide immunotherapeutic effects while also safeguarding diverse cell populations. These adaptable nanozymes have already exhibited efficacy in treating common types of arthritis, and their distinctive synergistic therapeutic effects offer great potential in the fight against arthritis associated with COVID-19. In this comprehensive review, we explore the potential of nanozymes in alleviating arthritis following SARS-CoV-2 infection by neutralizing the underlying factors associated with the disease. We also provide a detailed analysis of the common therapeutic pathways employed by these nanozymes and offer insights into how they can be further optimized to effectively address COVID-19-associated arthritis.
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Affiliation(s)
- Dan Li
- Department of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, China.
| | - Baofeng Zhao
- Liaoning Provincial Key Laboratory of Medical Testing, Jinzhou Medical University, Jinzhou, 121001, China.
| | - Pengfei Zhuang
- Department of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, China.
| | - Xifan Mei
- Liaoning Provincial Key Laboratory of Medical Testing, Jinzhou Medical University, Jinzhou, 121001, China.
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23
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Shabani Z, Liu J, Su H. Vascular Dysfunctions Contribute to the Long-Term Cognitive Deficits Following COVID-19. BIOLOGY 2023; 12:1106. [PMID: 37626992 PMCID: PMC10451811 DOI: 10.3390/biology12081106] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/31/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another very common but debilitating complication caused by SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized COVID-19 patients and range from shortness of concentration and overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and "brain fog" are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra-pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully and their underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.
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Affiliation(s)
- Zahra Shabani
- Center for Cerebrovascular Research, University of California (San Francisco), San Francisco, CA 94131, USA;
- Department of Anesthesia and Perioperative Care, University of California (San Francisco), San Francisco, CA 94131, USA
| | - Jialing Liu
- Department of Neurosurgery, University of California (San Francisco), San Francisco, CA 94131, USA;
| | - Hua Su
- Center for Cerebrovascular Research, University of California (San Francisco), San Francisco, CA 94131, USA;
- Department of Anesthesia and Perioperative Care, University of California (San Francisco), San Francisco, CA 94131, USA
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24
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Mozzi A, Oldani M, Forcella ME, Vantaggiato C, Cappelletti G, Pontremoli C, Valenti F, Forni D, Saresella M, Biasin M, Sironi M, Fusi P, Cagliani R. SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress, and autophagic flux. iScience 2023; 26:107118. [PMID: 37361873 PMCID: PMC10265927 DOI: 10.1016/j.isci.2023.107118] [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: 11/22/2022] [Revised: 05/08/2023] [Accepted: 06/09/2023] [Indexed: 06/28/2023] Open
Abstract
Coronaviruses encode a variable number of accessory proteins that are involved in host-virus interaction, suppression of immune responses, or immune evasion. SARS-CoV-2 encodes at least twelve accessory proteins, whose roles during infection have been studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive. Herein, we show that the ORF3c protein has a mitochondrial localization and alters mitochondrial metabolism, inducing a shift from glucose to fatty acids oxidation and enhanced oxidative phosphorylation. These effects result in increased ROS production and block of the autophagic flux. In particular, ORF3c affects lysosomal acidification, blocking the normal autophagic degradation process and leading to autolysosome accumulation. We also observed different effect on autophagy for SARS-CoV-2 and batCoV RaTG13 ORF3c proteins; the 36R and 40K sites are necessary and sufficient to determine these effects.
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Affiliation(s)
- Alessandra Mozzi
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
| | - Monica Oldani
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy
| | - Matilde E. Forcella
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy
| | - Chiara Vantaggiato
- Scientific Institute IRCCS E. MEDEA, Laboratory of Molecular Biology, 23842 Bosisio Parini, Italy
| | - Gioia Cappelletti
- Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157 Milan, Italy
| | - Chiara Pontremoli
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
| | - Francesca Valenti
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
| | - Diego Forni
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
| | - Marina Saresella
- Don C. Gnocchi Foundation ONLUS, IRCCS, Laboratory of Molecular Medicine and Biotechnology, 20148 Milan, Italy
| | - Mara Biasin
- Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, 20157 Milan, Italy
| | - Manuela Sironi
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
| | - Paola Fusi
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milano, Italy
| | - Rachele Cagliani
- Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy
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25
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Wilson GN. A Clinical Qualification Protocol Highlights Overlapping Genomic Influences and Neuro-Autonomic Mechanisms in Ehlers-Danlos and Long COVID-19 Syndromes. Curr Issues Mol Biol 2023; 45:6003-6023. [PMID: 37504295 PMCID: PMC10378515 DOI: 10.3390/cimb45070379] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/12/2023] [Accepted: 07/14/2023] [Indexed: 07/29/2023] Open
Abstract
A substantial fraction of the 15% with double-jointedness or hypermobility have the traditionally ascertained joint-skeletal, cutaneous, and cardiovascular symptoms of connective tissue dysplasia and its particular manifestation as Ehlers-Danlos syndrome (EDS). The holistic ascertainment of 120 findings in 1261 EDS patients added neuro-autonomic symptoms like headaches, muscle weakness, brain fog, chronic fatigue, dyspnea, and bowel irregularity to those of arthralgia and skin laxity, 15 of these symptoms shared with those of post-infectious SARS-CoV-2 (long COVID-19). Underlying articulo-autonomic mechanisms guided a clinical qualification protocol that qualified DNA variants in 317 genes as having diagnostic utility for EDS, six of them identical (F2-LIFR-NLRP3-STAT1-T1CAM1-TNFRSF13B) and eighteen similar to those modifying COVID-19 severity/EDS, including ADAMTS13/ADAMTS2-C3/C1R-IKBKG/IKBKAP-PIK3C3/PIK3R1-POLD4/POLG-TMPRSS2/TMPRSS6-WNT3/WNT10A. Also, contributing to EDS and COVID-19 severity were forty and three genes, respectively, impacting mitochondrial functions as well as parts of an overlapping gene network, or entome, that are hypothesized to mediate the cognitive-behavioral, neuro-autonomic, and immune-inflammatory alterations of connective tissue in these conditions. The further characterization of long COVID-19 natural history and genetic predisposition will be necessary before these parallels to EDS can be carefully delineated and translated into therapies.
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Affiliation(s)
- Golder N Wilson
- Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, and KinderGenome Genetics Private Practice, 5347 W Mockingbird, Dallas, TX 75209, USA
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26
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Hu W, Lin X, Qian M, Du TM, Lan X. Treatment of Candida albicans liver abscess complicated with COVID-19 after liver metastasis ablation: A case report. World J Gastrointest Oncol 2023; 15:1311-1316. [PMID: 37546559 PMCID: PMC10401469 DOI: 10.4251/wjgo.v15.i7.1311] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/14/2023] [Accepted: 05/26/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Liver interventional surgery is a relatively safe and minimally invasive surgery. However, for patients who have undergone Whipple surgery, the probability of developing a liver abscess after liver interventional surgery is very high. Fungal liver abscess has a high mortality rate, especially when complicated with malignant tumors, diabetes, coronavirus disease 2019 (COVID-19) and other complications. Fungal liver abscess is rare, and there are no guidelines or expert consensus on the course of antifungal therapy.
CASE SUMMARY A 54-year-old woman with pancreatic head cancer received albumin-bound paclitaxel in combination with gemcitabine chemotherapy after laparoscopic pancreaticoduodenectomy. Liver metastasis was found 1 mo after completion of 8 cycles of chemotherapy, followed by ablation of the liver metastasis. After half a month of liver metastasis ablation, the patient experienced fever after chemotherapy and was diagnosed with liver abscess complicated with COVID-19 by contrast-enhanced abdominal computed tomography and real-time polymerase chain reaction detection. The results of pus culture showed Candida albicans, which was sensitive to fluconazole. The patient underwent percutaneous catheter drainage, antifungal therapy with fluconazole, and antiviral therapy with azvudine. During antifungal therapy, the patient showed a significant increase in liver enzyme levels and was discharged after liver protection therapy. Oral fluconazole was continued for 1 wk outside the hospital, and fluconazole was used for a total of 5 wk. The patient recovered well and received 4 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan after 2 mo of antifungal therapy.
CONCLUSION Effective treatment of Candida albicans liver abscess requires early detection, percutaneous catheter drainage, and 5 wk of antifungal therapy. Meanwhile, complications such as COVID-19 should be actively managed and nutritional support should be provided.
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Affiliation(s)
- Wen Hu
- Department of Oncology, Chengdu Seventh People’s Hospital, Chengdu 610000, Sichuan Province, China
| | - Xi Lin
- Department of Oncology, Yanting County People’s Hospital, Mianyang 621600, Sichuan Province, China
| | - Meng Qian
- Department of Oncology, Chengdu Seventh People’s Hospital, Chengdu 610000, Sichuan Province, China
| | - Tao-Ming Du
- Department of Radiology, Chengdu Seventh People’s Hospital, Chengdu 610000, Sichuan Province, China
| | - Xi Lan
- Department of Oncology, Chengdu Seventh People’s Hospital, Chengdu 610000, Sichuan Province, China
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Han R, Li W, Tian H, Zhao Y, Zhang H, Pan W, Wang X, Xu L, Ma Z, Bao Z. Urinary microRNAs in sepsis function as a novel prognostic marker. Exp Ther Med 2023; 26:346. [PMID: 37383369 PMCID: PMC10294602 DOI: 10.3892/etm.2023.12045] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 03/16/2023] [Indexed: 06/30/2023] Open
Abstract
Renal dysfunction is a common complication of sepsis. Early diagnosis and prompt treatment of sepsis with renal insufficiency are crucial for improving patient outcomes. Diagnostic markers can help identify patients at risk for sepsis and AKI, allowing for early intervention and potentially preventing the development of severe complications. The aim of the present study was to investigate the expression difference of urinary microRNAs (miRNAs/miRs) in elderly patients with sepsis and secondary renal insufficiency, and to evaluate their diagnostic value in these patients. In the present study, RNA was extracted from urine samples of elderly sepsis-related acute renal damage patients and the expression profiles of several miRNAs were analyzed. In order to evaluate the expression profile of several miRNAs, urine samples from elderly patients with acute renal damage brought on by sepsis were obtained. RNA extraction and sequencing were then performed on the samples. Furthermore, multiple bioinformatics methods were used to analyze miRNA profiles, including differential expression analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of different miRNA target genes, to further explore miRNAs that are suitable for utilization as biomarkers. A total of four miRNAs, including hsa-miR-31-5p, hsa-miR-151a-3p, hsa-miR-142-5p and hsa-miR-16-5p, were identified as potential biological markers and were further confirmed in sepsis using reverse transcription-quantitative PCR. The results of the present study demonstrated that the four urinary miRNAs were differentially expressed and may serve as specific markers for prediction of secondary acute kidney injury in elderly patients with sepsis.
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Affiliation(s)
- Rui Han
- Department of Emergency, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Wanqiu Li
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Hui Tian
- Department of Gerontology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
| | - Yun Zhao
- Department of Emergency, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China
| | - Hui Zhang
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Wei Pan
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Xianyi Wang
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Linfeng Xu
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Zhongliang Ma
- Laboratory for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China
| | - Zhijun Bao
- Department of Gerontology, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China
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Oud L, Garza J. The Impact of COVID-19 on Sepsis-Related Mortality in the United States. J Clin Med Res 2023; 15:328-331. [PMID: 37434769 PMCID: PMC10332882 DOI: 10.14740/jocmr4937] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 06/16/2023] [Indexed: 07/13/2023] Open
Abstract
Background Coronavirus disease 2019 (COVID-19)-related organ dysfunction is increasingly considered as sepsis of viral origin. In recent clinical and autopsy studies, sepsis has been present in the majority of decedents with COVID-19. Given the high mortality toll of COVID-19, sepsis epidemiology would be expected to be substantially transformed. However, the impact of COVID-19 on sepsis-related mortality at the national level has not been quantified. We aimed to estimate the contribution of COVID-19 to sepsis-related mortality in the USA during the first year of the pandemic. Methods We used the Centers for Disease Control Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) Multiple Cause of Death dataset to identify decedents with sepsis during 2015 - 2019, and those with a diagnosis of sepsis, COVID-19, or both in 2020. Negative binomial regression was used on the 2015 - 2019 data to forecast the number of sepsis-related deaths in 2020. We then compared the observed vs. predicted number of sepsis-related deaths in 2020. In addition, we examined the frequency of a diagnosis of COVID-19 among decedents with sepsis and the proportion of a diagnosis of sepsis among decedents with COVID-19. The latter analysis was repeated within each of the Department of Health and Human Services (HHS) regions. Results In 2020, there were 242,630 sepsis-related deaths, 384,536 COVID-19-related deaths, and 35,807 deaths with both in the USA. The predicted number of sepsis-related deaths for 2020 was 206,549 (95% confidence interval (CI): 201,550 - 211,671). COVID-19 was reported in 14.7% of decedents with sepsis, while a diagnosis of sepsis was reported in 9.3% of all COVID-19-related deaths, ranging from 6.7% to 12.8% across HHS regions. Conclusions A diagnosis of COVID-19 was reported in less than one in six of decedents with sepsis in 2020, with corresponding less than one in 10 diagnoses of sepsis among decedents with COVID-19. These findings suggest that death certificate-based data may have substantially underestimated the toll of sepsis-related deaths in the USA during the first year of the pandemic.
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Affiliation(s)
- Lavi Oud
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Texas Tech University Health Sciences Center at the Permian Basin, Odessa, TX, USA
| | - John Garza
- Department of Mathematics, The University of Texas of the Permian Basin, Odessa, TX, USA
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Bolesławska I, Kowalówka M, Bolesławska-Król N, Przysławski J. Ketogenic Diet and Ketone Bodies as Clinical Support for the Treatment of SARS-CoV-2-Review of the Evidence. Viruses 2023; 15:1262. [PMID: 37376562 PMCID: PMC10326824 DOI: 10.3390/v15061262] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/23/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
One of the proposed nutritional therapies to support drug therapy in COVID-19 is the use of a ketogenic diet (KD) or ketone bodies. In this review, we summarized the evidence from tissue, animal, and human models and looked at the mechanisms of action of KD/ketone bodies against COVID-19. KD/ketone bodies were shown to be effective at the stage of virus entry into the host cell. The use of β-hydroxybutyrate (BHB), by preventing the metabolic reprogramming associated with COVID-19 infection and improving mitochondrial function, reduced glycolysis in CD4+ lymphocytes and improved respiratory chain function, and could provide an alternative carbon source for oxidative phosphorylation (OXPHOS). Through multiple mechanisms, the use of KD/ketone bodies supported the host immune response. In animal models, KD resulted in protection against weight loss and hypoxemia, faster recovery, reduced lung injury, and resulted in better survival of young mice. In humans, KD increased survival, reduced the need for hospitalization for COVID-19, and showed a protective role against metabolic abnormalities after COVID-19. It appears that the use of KD and ketone bodies may be considered as a clinical nutritional intervention to assist in the treatment of COVID-19, despite the fact that numerous studies indicate that SARS-CoV-2 infection alone may induce ketoacidosis. However, the use of such an intervention requires strong scientific validation.
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Affiliation(s)
- Izabela Bolesławska
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (M.K.); (J.P.)
| | - Magdalena Kowalówka
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (M.K.); (J.P.)
| | - Natasza Bolesławska-Król
- Student Society of Radiotherapy, Collegium Medicum, University of Zielona Gora, Zyta 28, 65-046 Zielona Góra, Poland;
| | - Juliusz Przysławski
- Department of Bromatology, Poznan University of Medical Sciences, 60-806 Poznan, Poland; (M.K.); (J.P.)
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Effects of underlying heart failure on outcomes of COVID-19; a systematic review and meta-analysis. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2023; 61:6-27. [PMID: 36453439 DOI: 10.2478/rjim-2022-0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Indexed: 12/03/2022]
Abstract
Background: The risk for worse outcomes of COVID-19 (Coronavirus 2019 disease) is higher in patients with cardiac conditions. In this study, we aim to investigate the risks of COVID-19-induced conditions in cases with underlying heart failure. Methods: We systematically searched PubMed, Scopus, Ovid, ProQuest, Web of Science, and the Cochrane library, to collect the English language articles that investigated patients with underlying heart failure who get infected by COVID-19. The second version of comprehensive meta-analysis (CMA.2) software was used to conduct the meta-analysis. Results: From 5997 publications, our eligibility criteria were met by 27 studies. Overall, outcomes investigated in all studies include but are not limited to mortality rate, length of hospitalization, need for Intensive care unit (ICU) admission, need for mechanical ventilation, and major cardiovascular conditions. Regarding mortality heart failure patients were more susceptible to death (OR:2.570, 95%CI: 2.085 to 3.169; p-value:<0.001). Also in heart failure patients, the risk of mechanical ventilation was higher (OR:1.707, 95%CI: 1.113 to 2.617; p-value: 0.014). Conclusion: Pre-existing heart failure is associated with the increased risk of mortality and the need for mechanical ventilation while getting infected with COVID-19. Finding an answer to determine the risk of hospitalization, length of stay, readmission rate, and multiorgan failure is necessary for further development of preventive care and making a plan for providing optimal healthcare facilities for these patients.
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31
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Lettieri-Barbato D, Ventura N, Faraonio R, Aquilano K. Editorial: Advances in metabolic mechanisms of aging and its related diseases, Volume II. Front Physiol 2023; 14:1145165. [PMID: 36760536 PMCID: PMC9903050 DOI: 10.3389/fphys.2023.1145165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Affiliation(s)
- Daniele Lettieri-Barbato
- Department of Biology, University of Rome Tor Vergata, Rome, Italy,IRCCS Fondazione Santa Lucia, Rome, Italy,*Correspondence: Daniele Lettieri-Barbato, ; Katia Aquilano,
| | - Natascia Ventura
- IUF—Leibniz Research Institute for Environmental Medicine, Dusseldorf, Germany,Medical Faculty, Institute of Clinical Chemistry and Laboratory Diagnostic, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany
| | - Raffaella Faraonio
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
| | - Katia Aquilano
- Department of Biology, University of Rome Tor Vergata, Rome, Italy,*Correspondence: Daniele Lettieri-Barbato, ; Katia Aquilano,
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32
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Therapeutic Potential of the Purinergic System in Major Depressive Disorder Associated with COVID-19. Cell Mol Neurobiol 2023; 43:621-637. [PMID: 35348977 PMCID: PMC8960668 DOI: 10.1007/s10571-022-01215-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 03/18/2022] [Indexed: 12/23/2022]
Abstract
Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.
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33
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Nunn AVW, Guy GW, Brysch W, Bell JD. Understanding Long COVID; Mitochondrial Health and Adaptation-Old Pathways, New Problems. Biomedicines 2022; 10:3113. [PMID: 36551869 PMCID: PMC9775339 DOI: 10.3390/biomedicines10123113] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 12/04/2022] Open
Abstract
Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as "brain fog", fatigue and clotting problems. Explanations for "long COVID" include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with sub-optimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can "tip" the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer's metabolism needs to be "tipped" back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response.
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Affiliation(s)
- Alistair V. W. Nunn
- Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London W1W 6UW, UK
| | - Geoffrey W. Guy
- The Guy Foundation, Chedington Court, Beaminster, Dorset DT8 3HY, UK
| | | | - Jimmy D. Bell
- Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London W1W 6UW, UK
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Otsubo R, Minamitani T, Kobiyama K, Fujita J, Ito T, Ueno S, Anzai I, Tanino H, Aoyama H, Matsuura Y, Namba K, Imadome KI, Ishii KJ, Tsumoto K, Kamitani W, Yasui T. Human antibody recognition and neutralization mode on the NTD and RBD domains of SARS-CoV-2 spike protein. Sci Rep 2022; 12:20120. [PMID: 36418391 PMCID: PMC9684487 DOI: 10.1038/s41598-022-24730-4] [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: 08/08/2022] [Accepted: 11/18/2022] [Indexed: 11/25/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.
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Affiliation(s)
- Ryota Otsubo
- grid.482562.fLaboratory of Infectious Diseases and Immunity, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan
| | - Takeharu Minamitani
- grid.482562.fLaboratory of Infectious Diseases and Immunity, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan ,grid.472122.0Present Address: Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikoyama, Imizu, Toyama 939-0363 Japan
| | - Kouji Kobiyama
- grid.26999.3d0000 0001 2151 536XDivision of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639 Japan ,grid.482562.fLaboratory of Adjuvant Innovation, CVAR, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan
| | - Junso Fujita
- grid.136593.b0000 0004 0373 3971Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Toshihiro Ito
- grid.482562.fLaboratory of Proteome Research, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan ,grid.258799.80000 0004 0372 2033Present Address: Laboratory of Experimental Immunology, Department of Regeneration Science and Engineering, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507 Japan
| | - Shiori Ueno
- grid.256642.10000 0000 9269 4097Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, 3-39-22 Syowa-cho, Maebashi, Gunma 371-8511 Japan
| | - Itsuki Anzai
- grid.136593.b0000 0004 0373 3971Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Hiroki Tanino
- grid.136593.b0000 0004 0373 3971Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Hiroshi Aoyama
- grid.136593.b0000 0004 0373 3971Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Yoshiharu Matsuura
- grid.136593.b0000 0004 0373 3971Centre for Infectious Disease Education and Research, Osaka University, 2-8 Yamadaoka, Suita, Osaka 565-0871 Japan ,grid.136593.b0000 0004 0373 3971Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Keiichi Namba
- grid.136593.b0000 0004 0373 3971Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan ,grid.136593.b0000 0004 0373 3971JEOL YOKOGUSHI Research Alliance Laboratories, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan ,grid.472717.0RIKEN SPring-8 Center, 1-3 Yamadaoka, Suita, Osaka 565-0871 Japan
| | - Ken-Ichi Imadome
- grid.63906.3a0000 0004 0377 2305Department of Advanced Medicine for Infections, National Center for Child Health and Development (NCCHD), 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535 Japan
| | - Ken J. Ishii
- grid.26999.3d0000 0001 2151 536XDivision of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639 Japan ,grid.482562.fLaboratory of Adjuvant Innovation, CVAR, NIBIOHN, 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan
| | - Kouhei Tsumoto
- grid.482562.fCenter for Drug Discovery Research (CDDR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan ,grid.26999.3d0000 0001 2151 536XDepartment of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656 Japan ,grid.26999.3d0000 0001 2151 536XMedical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639 Japan
| | - Wataru Kamitani
- grid.256642.10000 0000 9269 4097Department of Infectious Diseases and Host Defense, Graduate School of Medicine, Gunma University, 3-39-22 Syowa-cho, Maebashi, Gunma 371-8511 Japan
| | - Teruhito Yasui
- grid.482562.fLaboratory of Infectious Diseases and Immunity, Center for Vaccine and Adjuvant Research (CVAR), National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085 Japan
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Rieder AS, Deniz BF, Netto CA, Wyse ATS. A Review of In Silico Research, SARS-CoV-2, and Neurodegeneration: Focus on Papain-Like Protease. Neurotox Res 2022; 40:1553-1569. [PMID: 35917086 PMCID: PMC9343570 DOI: 10.1007/s12640-022-00542-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/17/2022] [Accepted: 06/30/2022] [Indexed: 01/18/2023]
Abstract
Since the appearance of SARS-CoV-2 and the COVID-19 pandemic, the search for new approaches to treat this disease took place in the scientific community. The in silico approach has gained importance at this moment, once the methodologies used in this kind of study allow for the identification of specific protein-ligand interactions, which may serve as a filter step for molecules that can act as specific inhibitors. In addition, it is a low-cost and high-speed technology. Molecular docking has been widely used to find potential viral protein inhibitors for structural and non-structural proteins of the SARS-CoV-2, aiming to block the infection and the virus multiplication. The papain-like protease (PLpro) participates in the proteolytic processing of SARS-CoV-2 and composes one of the main targets studied for pharmacological intervention by in silico methodologies. Based on that, we performed a systematic review about PLpro inhibitors from the perspective of in silico research, including possible therapeutic molecules in relation to this viral protein. The neurological problems triggered by COVID-19 were also briefly discussed, especially relative to the similarities of neuroinflammation present in Alzheimer's disease. In this context, we focused on two molecules, curcumin and glycyrrhizinic acid, given their PLpro inhibitory actions and neuroprotective properties and potential therapeutic effects on COVID-19.
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Affiliation(s)
- Alessandra S Rieder
- Laboratory of Neuroprotection and Neurometabolic Diseases, Wyse's Lab, Department of Biochemistry, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - Bruna F Deniz
- Laboratory of Neuroprotection and Neurometabolic Diseases, Wyse's Lab, Department of Biochemistry, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - Carlos Alexandre Netto
- Laboratory of Neuroprotection and Neurometabolic Diseases, Wyse's Lab, Department of Biochemistry, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil
| | - Angela T S Wyse
- Laboratory of Neuroprotection and Neurometabolic Diseases, Wyse's Lab, Department of Biochemistry, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
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Anwar MM, Sah R, Shrestha S, Ozaki A, Roy N, Fathah Z, Rodriguez-Morales AJ. Disengaging the COVID-19 Clutch as a Discerning Eye Over the Inflammatory Circuit During SARS-CoV-2 Infection. Inflammation 2022; 45:1875-1894. [PMID: 35639261 PMCID: PMC9153229 DOI: 10.1007/s10753-022-01674-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 03/29/2022] [Accepted: 04/18/2022] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the cytokine release syndrome (CRS) and leads to multiorgan dysfunction. Mitochondrial dynamics are fundamental to protect against environmental insults, but they are highly susceptible to viral infections. Defective mitochondria are potential sources of reactive oxygen species (ROS). Infection with SARS-CoV-2 damages mitochondria, alters autophagy, reduces nitric oxide (NO), and increases both nicotinamide adenine dinucleotide phosphate oxidases (NOX) and ROS. Patients with coronavirus disease 2019 (COVID-19) exhibited activated toll-like receptors (TLRs) and the Nucleotide-binding and oligomerization domain (NOD-), leucine-rich repeat (LRR-), pyrin domain-containing protein 3 (NLRP3) inflammasome. The activation of TLRs and NLRP3 by SARS-CoV-2 induces interleukin 6 (IL-6), IL-1β, IL-18, and lactate dehydrogenase (LDH). Herein, we outline the inflammatory circuit of COVID-19 and what occurs behind the scene, the interplay of NOX/ROS and their role in hypoxia and thrombosis, and the important role of ROS scavengers to reduce COVID-19-related inflammation.
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Affiliation(s)
- Mohammed Moustapha Anwar
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, Egypt.
| | - Ranjit Sah
- Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Sunil Shrestha
- Department of Pharmaceutical and Health Service Research, Nepal Health Research and Innovation Foundation, Lalitpur, Nepal
| | - Akihiko Ozaki
- Department of Breast Surgery, Jyoban Hospital of Tokiwa Foundation, Iwaki, Japan
- Medical Governance Research Institute, Tokyo, Japan
| | - Namrata Roy
- SRM University, SRM Nagar, Kattankulathur, Chengalpattu, Tamil Nadu, 603203, India
| | - Zareena Fathah
- Kings College London, London, UK
- College of Medicine and Health Sciences, United Arab University, Abu Dhabi, United Arab Emirates
| | - Alfonso J Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundacion Universitaria Autonoma de Las Americas, Pereira, Risaralda, Colombia.
- Institución Universitaria Visión de Las Americas, Pereira, Risaralda, Colombia.
- Faculty of Health Sciences, Universidad Cientifica del Sur, Lima, Peru.
- School of Medicine, Universidad Privada Franz Tamayo (UNIFRANZ), Cochabamba, Bolivia.
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Franzini M, Valdenassi L, Pandolfi S, Tirelli U, Ricevuti G, Simonetti V, Berretta M, Vaiano F, Chirumbolo S. The biological activity of medical ozone in the hormetic range and the role of full expertise professionals. Front Public Health 2022; 10:979076. [PMID: 36187636 PMCID: PMC9523567 DOI: 10.3389/fpubh.2022.979076] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 08/19/2022] [Indexed: 01/25/2023] Open
Affiliation(s)
- Marianno Franzini
- International Scientific Society of Oxygen-Ozone Therapy (SIOOT), University of Pavia, Pavia, Italy
| | - Luigi Valdenassi
- International Scientific Society of Oxygen-Ozone Therapy (SIOOT), University of Pavia, Pavia, Italy
| | - Sergio Pandolfi
- International Scientific Society of Oxygen-Ozone Therapy (SIOOT), University of Pavia, Pavia, Italy,*Correspondence: Sergio Pandolfi
| | | | | | - Vincenzo Simonetti
- International Scientific Society of Oxygen-Ozone Therapy (SIOOT), University of Pavia, Pavia, Italy
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Francesco Vaiano
- International Scientific Society of Oxygen-Ozone Therapy (SIOOT), University of Pavia, Pavia, Italy
| | - Salvatore Chirumbolo
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy,Salvatore Chirumbolo
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Liao TH, Wu HC, Liao MT, Hu WC, Tsai KW, Lin CC, Lu KC. The Perspective of Vitamin D on suPAR-Related AKI in COVID-19. Int J Mol Sci 2022; 23:10725. [PMID: 36142634 PMCID: PMC9500944 DOI: 10.3390/ijms231810725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/08/2022] [Accepted: 09/13/2022] [Indexed: 01/08/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of millions of people around the world. Severe vitamin D deficiency can increase the risk of death in people with COVID-19. There is growing evidence that acute kidney injury (AKI) is common in COVID-19 patients and is associated with poorer clinical outcomes. The kidney effects of SARS-CoV-2 are directly mediated by angiotensin 2-converting enzyme (ACE2) receptors. AKI is also caused by indirect causes such as the hypercoagulable state and microvascular thrombosis. The increased release of soluble urokinase-type plasminogen activator receptor (suPAR) from immature myeloid cells reduces plasminogen activation by the competitive inhibition of urokinase-type plasminogen activator, which results in low plasmin levels and a fibrinolytic state in COVID-19. Frequent hypercoagulability in critically ill patients with COVID-19 may exacerbate the severity of thrombosis. Versican expression in proximal tubular cells leads to the proliferation of interstitial fibroblasts through the C3a and suPAR pathways. Vitamin D attenuates the local expression of podocyte uPAR and decreases elevated circulating suPAR levels caused by systemic inflammation. This decrease preserves the function and structure of the glomerular barrier, thereby maintaining renal function. The attenuated hyperinflammatory state reduces complement activation, resulting in lower serum C3a levels. Vitamin D can also protect against COVID-19 by modulating innate and adaptive immunity, increasing ACE2 expression, and inhibiting the renin-angiotensin-aldosterone system. We hypothesized that by reducing suPAR levels, appropriate vitamin D supplementation could prevent the progression and reduce the severity of AKI in COVID-19 patients, although the data available require further elucidation.
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Affiliation(s)
- Tzu-Hsien Liao
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
| | - Hsien-Chang Wu
- Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 970, Taiwan
| | - Min-Tser Liao
- Department of Pediatrics, Taoyuan Armed Forces General Hospital Hsinchu Branch, Hsinchu City 300, Taiwan
- Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
| | - Wan-Chung Hu
- Department of Clinical Pathology and Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
| | - Kuo-Wang Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
| | - Ching-Chieh Lin
- Department of Chest Medicine, Taoyuan Armed Forces General Hospital Hsinchu Branch, Hsinchu City 300, Taiwan
| | - Kuo-Cheng Lu
- Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
- Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
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ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection. PLoS Biol 2022; 20:e3001754. [PMID: 36099266 PMCID: PMC9469972 DOI: 10.1371/journal.pbio.3001754] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 07/12/2022] [Indexed: 12/24/2022] Open
Abstract
Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19). Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchoalveolar lavage fluid (BALF) from critically ill COVID-19 patients was associated with reduced intensive care unit (ICU) and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection. Autophagy proteins mediate the production of extracellular vesicles termed defensosomes in response to innate immune ligands. This study reveals that ACE2-containing defensosomes bind and inhibit SARS-CoV-2 infection, and are associated with reduced length of hospital stay for patients with COVID-19.
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Cao T, Liu L, To KK, Lim C, Zhou R, Ming Y, Kwan K, Yu S, Chan C, Zhou B, Huang H, Mo Y, Du Z, Gong R, Yat L, Hung IF, Tam AR, To W, Leung W, Chik TS, Tsang OT, Lin X, Song Y, Yuen K, Chen Z. Mitochondrial regulation of acute extrafollicular B-cell responses to COVID-19 severity. Clin Transl Med 2022; 12:e1025. [PMID: 36103567 PMCID: PMC9473490 DOI: 10.1002/ctm2.1025] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 08/01/2022] [Accepted: 08/08/2022] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Patients with COVID-19 display a broad spectrum of manifestations from asymptomatic to life-threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. METHODS We investigated a total of 137 APs infected with SARS-CoV-2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD-, S1-, SSA/Ro- and dsDNA-specific IgG. RESULTS While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection-induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID-19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. CONCLUSION Our results reveal an immune mechanism that controls SARS-CoV-2-induced detrimental B cell responses and COVID-19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.
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Affiliation(s)
- Tianyu Cao
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of ImmunologyFourth Military Medical UniversityXi'anPeople's Republic of China
- Department of DermatologyTangdu Hospital, Fourth Military Medical UniversityXi'anPeople's Republic of China
| | - Li Liu
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Centre for VirologyVaccinology and Therapeutics LimitedHong Kong Special Administrative RegionPeople's Republic of China
| | - Kelvin Kai‐Wang To
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of ImmunologyFourth Military Medical UniversityXi'anPeople's Republic of China
- State Key Laboratory of Emerging Infectious Diseases, Department of MicrobiologyThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Centre for VirologyVaccinology and Therapeutics LimitedHong Kong Special Administrative RegionPeople's Republic of China
| | - Chun‐Yu Lim
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Runhong Zhou
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Yue Ming
- School of Biomedical SciencesUniversity of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Ka‐Yi Kwan
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Sulan Yu
- School of Chinese MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Chun‐Yin Chan
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Biao Zhou
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Haode Huang
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Yufei Mo
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Zhenglong Du
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Ruomei Gong
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Luk‐Tsz Yat
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Ivan Fan‐Ngai Hung
- Department of Medicine, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Anthony Raymond Tam
- Department of MedicineQueen Mary HospitalHong Kong Special Administrative RegionPeople's Republic of China
| | - Wing‐Kin To
- Department of PathologyPrincess Margaret HospitalHong Kong Special Administrative RegionPeople's Republic of China
| | - Wai‐Shing Leung
- Department of Medicine and GeriatricsPrincess Margaret HospitalHong Kong Special Administrative RegionPeople's Republic of China
| | - Thomas Shiu‐Hong Chik
- Department of Medicine and GeriatricsPrincess Margaret HospitalHong Kong Special Administrative RegionPeople's Republic of China
| | - Owen Tak‐Yin Tsang
- Department of Medicine and GeriatricsPrincess Margaret HospitalHong Kong Special Administrative RegionPeople's Republic of China
| | - Xiang Lin
- School of Chinese MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - You‐qiang Song
- School of Biomedical SciencesUniversity of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
| | - Kwok‐Yung Yuen
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- State Key Laboratory of Emerging Infectious Diseases, Department of MicrobiologyThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Centre for VirologyVaccinology and Therapeutics LimitedHong Kong Special Administrative RegionPeople's Republic of China
| | - Zhiwei Chen
- AIDS Institute, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Department of Microbiology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- State Key Laboratory of Emerging Infectious Diseases, Department of MicrobiologyThe University of Hong KongHong Kong Special Administrative RegionPeople's Republic of China
- Centre for VirologyVaccinology and Therapeutics LimitedHong Kong Special Administrative RegionPeople's Republic of China
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Adesse D, Gladulich L, Alvarez-Rosa L, Siqueira M, Marcos AC, Heider M, Motta CS, Torices S, Toborek M, Stipursky J. Role of aging in Blood-Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19. Fluids Barriers CNS 2022; 19:63. [PMID: 35982454 PMCID: PMC9386676 DOI: 10.1186/s12987-022-00357-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 07/18/2022] [Indexed: 12/21/2022] Open
Abstract
COVID-19, which is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), has resulted in devastating morbidity and mortality worldwide due to lethal pneumonia and respiratory distress. In addition, the central nervous system (CNS) is well documented to be a target of SARS-CoV-2, and studies detected SARS-CoV-2 in the brain and the cerebrospinal fluid of COVID-19 patients. The blood-brain barrier (BBB) was suggested to be the major route of SARS-CoV-2 infection of the brain. Functionally, the BBB is created by an interactome between endothelial cells, pericytes, astrocytes, microglia, and neurons, which form the neurovascular units (NVU). However, at present, the interactions of SARS-CoV-2 with the NVU and the outcomes of this process are largely unknown. Moreover, age was described as one of the most prominent risk factors for hospitalization and deaths, along with other comorbidities such as diabetes and co-infections. This review will discuss the impact of SARS-CoV-2 on the NVU, the expression profile of SARS-CoV-2 receptors in the different cell types of the CNS and the possible role of aging in the neurological outcomes of COVID-19. A special emphasis will be placed on mitochondrial functions because dysfunctional mitochondria are also a strong inducer of inflammatory reactions and the "cytokine storm" associated with SARS-CoV-2 infection. Finally, we will discuss possible drug therapies to treat neural endothelial function in aged patients, and, thus, alleviate the neurological symptoms associated with COVID-19.
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Affiliation(s)
- Daniel Adesse
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil.
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
| | - Luis Gladulich
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil
| | - Liandra Alvarez-Rosa
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Michele Siqueira
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Anne Caroline Marcos
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil
| | - Marialice Heider
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil
| | - Caroline Soares Motta
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Avenida Brasil, 4365, Pavilhão Carlos Chagas, sala 307b, Rio de Janeiro, RJ, 21040-360, Brazil
| | - Silvia Torices
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Michal Toborek
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
- Institute of Physiotherapy and Health Sciences, The Jerzy Kukuczka Academy of Physical Education, Katowice, Poland
| | - Joice Stipursky
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Dellino M, Cascardi E, Vinciguerra M, Lamanna B, Malvasi A, Scacco S, Acquaviva S, Pinto V, Di Vagno G, Cormio G, De Luca R, Lafranceschina M, Cazzato G, Ingravallo G, Maiorano E, Resta L, Daniele A, La Forgia D. Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview. Int J Mol Sci 2022; 23:9136. [PMID: 36012402 PMCID: PMC9409275 DOI: 10.3390/ijms23169136] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/10/2022] [Accepted: 08/12/2022] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.
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Affiliation(s)
- Miriam Dellino
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70100 Bari, Italy
- Clinic of Obstetrics and Gynecology, “San Paolo” Hospital, 70123 Bari, Italy
| | - Eliano Cascardi
- Department of Medical Sciences, University of Turin, 10124 Turin, Italy
- Pathology Unit, FPO-IRCCS Candiolo Cancer Institute, Str. Provinciale 142, Km 3.95, 10060 Candiolo, Italy
| | - Marina Vinciguerra
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70100 Bari, Italy
| | - Bruno Lamanna
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70100 Bari, Italy
- Fetal Medicine Research Institute, King’s College Hospital, London SE5 9RS, UK
| | - Antonio Malvasi
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70100 Bari, Italy
| | - Salvatore Scacco
- Department of Basic Medical Sciences and Neurosciences, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Silvia Acquaviva
- Department of Basic Medical Sciences and Neurosciences, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Vincenzo Pinto
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70100 Bari, Italy
| | - Giovanni Di Vagno
- Clinic of Obstetrics and Gynecology, “San Paolo” Hospital, 70123 Bari, Italy
| | - Gennaro Cormio
- Gynecologic Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Department of Interdisciplinary Medicine (DIM), University of Bari “Aldo Moro”, 70121 Bari, Italy
| | | | | | - Gerardo Cazzato
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Giuseppe Ingravallo
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Eugenio Maiorano
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70121 Bari, Italy
| | - Leonardo Resta
- Department of Emergency and Organ Transplantation, University of Bari “Aldo Moro”, 70121 Bari, Italy
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Yu J, Tu W, Payne A, Rudyk C, Cuadros Sanchez S, Khilji S, Kumarathasan P, Subedi S, Haley B, Wong A, Anghel C, Wang Y, Chauhan V. Adverse Outcome Pathways and Linkages to Transcriptomic Effects Relevant to Ionizing Radiation Injury. Int J Radiat Biol 2022; 98:1789-1801. [PMID: 35939063 DOI: 10.1080/09553002.2022.2110313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
BACKGROUND In the past three decades, a large body of data on the effects of exposure to ionizing radiation and the ensuing changes in gene expression has been generated. These data have allowed for an understanding of molecular-level events and shown a level of consistency in response despite the vast formats and experimental procedures being used across institutions. However, clarity on how this information may inform strategies for health risk assessment needs to be explored. An approach to bridge this gap is the adverse outcome pathway (AOP) framework. AOPs represent an illustrative framework characterizing a stressor associated with a sequential set of causally linked key events (KEs) at different levels of biological organization, beginning with a molecular initiating event (MIE) and culminating in an adverse outcome (AO). Here, we demonstrate the interpretation of transcriptomic datasets in the context of the AOP framework within the field of ionizing radiation by using a lung cancer AOP (AOP 272: https://www.aopwiki.org/aops/272) as a case example. METHODS Through the mining of the literature, radiation exposure-related transcriptomic studies in line with AOP 272 related to lung cancer, DNA damage response, and repair were identified. The differentially expressed genes within relevant studies were collated and subjected to the pathway and network analysis using Reactome and GeneMANIA platforms. Identified pathways were filtered (p < 0.001, ≥ 3 genes) and categorized based on relevance to KEs in the AOP. Gene connectivities were identified and further grouped by gene expression-informed associated events (AEs). Relevant quantitative dose-response data were used to inform the directionality in the expression of the genes in the network across AEs. RESULTS Reactome analyses identified 7 high-level biological processes with multiple pathways and associated genes that mapped to potential KEs in AOP 272. The gene connectivities were further represented as a network of AEs with associated expression profiles that highlighted patterns of gene expression levels. CONCLUSIONS This study demonstrates the application of transcriptomics data in AOP development and provides information on potential data gaps. Although the approach is new and anticipated to evolve, it shows promise for improving the understanding of underlying mechanisms of disease progression with a long-term vision to be predictive of adverse outcomes.
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Affiliation(s)
- Jihang Yu
- Canadian Nuclear Laboratories, Chalk River, Ontario, Canada
| | - Wangshu Tu
- Carleton University, Ottawa, Ontario, Canada
| | | | - Chris Rudyk
- Carleton University, Ottawa, Ontario, Canada
| | | | | | | | | | - Brittany Haley
- Canadian Nuclear Laboratories, Chalk River, Ontario, Canada
| | - Alicia Wong
- Canadian Nuclear Laboratories, Chalk River, Ontario, Canada.,McMaster University, Hamilton, Ontario, Canada
| | | | - Yi Wang
- Canadian Nuclear Laboratories, Chalk River, Ontario, Canada.,University of Ottawa, Ottawa, Ontario, Canada
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Tereshin AE, Kiryanova VV, Reshetnik DA. Correction of Mitochondrial Dysfunction in the Complex Rehabilitation of COVID-19 Patients. NEUROSCIENCE AND BEHAVIORAL PHYSIOLOGY 2022; 52:511-514. [PMID: 35892008 PMCID: PMC9304544 DOI: 10.1007/s11055-022-01269-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 05/24/2021] [Indexed: 11/24/2022]
Abstract
Objective. To study the efficacy of courses of i.v., Cytoflavin in combination with the standard rehabilitation program for postcovid syndrome for correction of postcovid asthenia. Materials and methods. Follow-up investigations were carried out in 45 patients with postcovid syndrome at the second stage of rehabilitation. Patients were divided into two groups of comparable sex and age. The volume of lung damage was also similar in both groups, at 25-80%. The 24 patients making up the comparison group received standard postcovid rehabilitation: pulsed magnetotherapy, inhalation therapy, aeroionotherapy, infrared laser therapy, courses of aerobic training, rational psychotherapy, and successive drug therapy. The 21 patients of the study group additionally received intravenous Cytoflavin daily for 10 days. The dynamics of increases in scores on the Rehabilitation Routing Scale, the Hamilton Depression Rating Scale (HDRS), the Asthenic Status Scale, and the 6-minute walk test at admission and discharge were also monitored. Results and conclusions. Addition of courses of intravenous Cytoflavin to the complex rehabilitation program for postcovid syndrome significantly improved the general functional state of the body, decreased levels of depression and asthenization, and increased physical exercise tolerance.
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Affiliation(s)
- A. E. Tereshin
- Mechnikov North-Western State Medical University, Russian Ministry of Health, St. Petersburg, Russia
- Nikolaevskaya Hospital, St. Petersburg, Russia
| | - V. V. Kiryanova
- Mechnikov North-Western State Medical University, Russian Ministry of Health, St. Petersburg, Russia
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Tanabe S, O’Brien J, Tollefsen KE, Kim Y, Chauhan V, Yauk C, Huliganga E, Rudel RA, Kay JE, Helm JS, Beaton D, Filipovska J, Sovadinova I, Garcia-Reyero N, Mally A, Poulsen SS, Delrue N, Fritsche E, Luettich K, La Rocca C, Yepiskoposyan H, Klose J, Danielsen PH, Esterhuizen M, Jacobsen NR, Vogel U, Gant TW, Choi I, FitzGerald R. Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events. FRONTIERS IN TOXICOLOGY 2022; 4:887135. [PMID: 35875696 PMCID: PMC9298159 DOI: 10.3389/ftox.2022.887135] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/13/2022] [Indexed: 02/05/2023] Open
Abstract
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself. A substantial discussion has therefore been undertaken in a series of workshops named "Mystery or ROS" to elucidate the role of RONS in disease and adverse effects associated with exposure to stressors such as nanoparticles, chemical, and ionizing and non-ionizing radiation. This review introduces the background for RONS production, reflects on the direct and indirect effects of RONS, addresses the diversity of terminology used in different fields of research, and provides guidance for developing a harmonized approach for defining a common event terminology within the AOP developer community.
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Affiliation(s)
- Shihori Tanabe
- Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki, Japan
| | - Jason O’Brien
- Wildlife Toxicology Research Section, Environment and Climate Change Canada, Toronto, ON, Canada
| | - Knut Erik Tollefsen
- Norwegian Institute for Water Research (NIVA), Oslo, Norway
- Norwegian University of Life Sciences (NMBU), Ås, Norway
- Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Ås, Norway
| | - Youngjun Kim
- Korea Institute of Science and Technology (KIST) Europe, Saarbrücken, Germany
| | | | | | | | | | | | | | | | | | - Iva Sovadinova
- RECETOX, Faculty of Science, Masaryk University, Brno, Czech Republic
| | - Natalia Garcia-Reyero
- U.S. Army Engineer Research and Development Center (ERDC), Vicksburg, MS, United States
| | - Angela Mally
- Department of Toxicology, University of Würzburg, Würzburg, Germany
| | - Sarah Søs Poulsen
- National Research Centre for the Working Environment, Copenhagen, Denmark
| | - Nathalie Delrue
- Organisation for Economic Co-operation and Development (OECD), Paris, France
| | - Ellen Fritsche
- Group of Alternative Method Development for Environmental Toxicity Testing, IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
| | - Karsta Luettich
- Philip Morris International R&D, Philip Morris Products SA, Neuchatel, Switzerland
| | - Cinzia La Rocca
- Center for Gender-specific Medicine, Italian National Institute of Health, Rome, Italy
| | - Hasmik Yepiskoposyan
- Philip Morris International R&D, Philip Morris Products SA, Neuchatel, Switzerland
| | - Jördis Klose
- Group of Alternative Method Development for Environmental Toxicity Testing, IUF—Leibniz-Research Institute for Environmental Medicine, Duesseldorf, Germany
| | | | - Maranda Esterhuizen
- University of Helsinki, Ecosystems and Environment Research Programme, Faculty of Biological and Environmental Sciences, Lahti, Finland, and Helsinki Institute of Sustainability Science (HELSUS), Helsinki, Finland
| | | | - Ulla Vogel
- National Research Centre for the Working Environment, Copenhagen, Denmark
| | - Timothy W. Gant
- UK Health Security Agency, Public Health England, London, United Kingdom
| | - Ian Choi
- Korea Institute of Science and Technology (KIST) Europe, Saarbrücken, Germany
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Mazumder S, Bindu S, De R, Debsharma S, Pramanik S, Bandyopadhyay U. Emerging role of mitochondrial DAMPs, aberrant mitochondrial dynamics and anomalous mitophagy in gut mucosal pathogenesis. Life Sci 2022; 305:120753. [PMID: 35787999 DOI: 10.1016/j.lfs.2022.120753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/13/2022] [Accepted: 06/27/2022] [Indexed: 12/22/2022]
Abstract
Gastroduodenal inflammation and ulcerative injuries are increasing due to expanding socio-economic stress, unhealthy food habits-lifestyle, smoking, alcoholism and usage of medicines like non-steroidal anti-inflammatory drugs. In fact, gastrointestinal (GI) complications, associated with the prevailing COVID-19 pandemic, further, poses a challenge to global healthcare towards safeguarding the GI tract. Emerging evidences have discretely identified mitochondrial dysfunctions as common etiological denominators in diseases. However, it is worth realizing that mitochondrial dysfunctions are not just consequences of diseases. Rather, damaged mitochondria severely aggravate the pathogenesis thereby qualifying as perpetrable factors worth of prophylactic and therapeutic targeting. Oxidative and nitrosative stress due to endogenous and exogenous stimuli triggers mitochondrial injury causing production of mitochondrial damage associated molecular patterns (mtDAMPs), which, in a feed-forward loop, inflicts inflammatory tissue damage. Mitochondrial structural dynamics and mitophagy are crucial quality control parameters determining the extent of mitopathology and disease outcomes. Interestingly, apart from endogenous factors, mitochondria also crosstalk and in turn get detrimentally affected by gut pathobionts colonized during luminal dysbiosis. Although mitopathology is documented in various pre-clinical/clinical studies, a comprehensive account appreciating the mitochondrial basis of GI mucosal pathologies is largely lacking. Here we critically discuss the molecular events impinging on mitochondria along with the interplay of mitochondria-derived factors in fueling mucosal pathogenesis. We specifically emphasize on the potential role of aberrant mitochondrial dynamics, anomalous mitophagy, mitochondrial lipoxidation and ferroptosis as emerging regulators of GI mucosal pathogenesis. We finally discuss about the prospect of mitochondrial targeting for next-generation drug discovery against GI disorders.
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Affiliation(s)
- Somnath Mazumder
- Department of Zoology, Raja Peary Mohan College, 1 Acharya Dhruba Pal Road, Uttarpara, West Bengal 712258, India
| | - Samik Bindu
- Department of Zoology, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal 736101, India
| | - Rudranil De
- Amity Institute of Biotechnology, Amity University, Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, West Bengal 700135, India
| | - Subhashis Debsharma
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Saikat Pramanik
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Uday Bandyopadhyay
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India; Division of Molecular Medicine, Bose Institute, EN 80, Sector V, Bidhan Nagar, Kolkata, West Bengal 700091, India.
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Diabetes Exacerbates Sepsis-Induced Neuroinflammation and Brain Mitochondrial Dysfunction. Inflammation 2022; 45:2352-2367. [PMID: 35689164 DOI: 10.1007/s10753-022-01697-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 05/06/2022] [Accepted: 06/01/2022] [Indexed: 11/05/2022]
Abstract
Sepsis is a life-threatening organ dysfunction, which demands notable attention for its treatment, especially in view of the involvement of immunodepressed patients, as the case of patients with diabetes mellitus (DM), who constitute a population susceptible to develop infections. Thus, considering this endocrine pathology as an implicatory role on the immune system, the aim of this study was to show the relationship between this disease and sepsis on neuroinflammatory and neurochemical parameters. Levels of IL-6, IL-10, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and mitochondrial respiratory chain complexes were evaluated in the hippocampus and prefrontal cortex 24 h after sepsis by cecal ligation and perforation (CLP) in Wistar rats induced to type 1 diabetes by alloxan (150 mg/kg). It was verified that diabetes implied immune function after 24 h of sepsis, since it contributed to the increase of the inflammatory process with higher production of IL-6 and decreased levels of IL-10 only in the hippocampus. In the same brain area, a several decrease in NGF level and activity of complexes I and II of the mitochondrial respiratory chain were observed. Thus, diabetes exacerbates neuroinflammation and results in mitochondrial impairment and downregulation of NGF level in the hippocampus after sepsis.
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Maamar M, Artime A, Pariente E, Fierro P, Ruiz Y, Gutiérrez S, Tobalina M, Díaz-Salazar S, Ramos C, Olmos JM, Hernández JL. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study. Curr Med Res Opin 2022; 38:901-909. [PMID: 35166141 PMCID: PMC8935459 DOI: 10.1080/03007995.2022.2042991] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.
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Affiliation(s)
- Meryam Maamar
- Emergency Service. Osakidetza, Servicio Vasco de Salud, Bilbao, País Vasco, Spain
| | - Arancha Artime
- El Llano - Primary Health Care Center, SESPA - Servicio Asturiano de Salud, Gijón Asturias, Spain
| | - Emilio Pariente
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Cantabria, Spain
- CONTACT Emilio Pariente “Camargo Interior” Primary Care Center, Associate Professor, University of Cantabria, Avda Bilbao, s/n. 39600-Muriedas, Cantabria, Spain
| | - Patricia Fierro
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
| | - Yolanda Ruiz
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
| | - Silvia Gutiérrez
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
| | - Marian Tobalina
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
| | - Sara Díaz-Salazar
- Camargo Interior - Primary Health Care Center, Servicio Cántabro de Salud, Muriedas, Cantabria, Spain
| | - Carmen Ramos
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Cantabria, Spain
- Camargo Costa - Primary Health Care Center, Servicio Cántabro de Salud, Maliaño, Cantabria, Spain
| | - José M. Olmos
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Cantabria, Spain
- Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
| | - José L. Hernández
- Depto. de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Cantabria, Spain
- Servicio de Medicina Interna, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), Santander, Cantabria, Spain
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Rajendran R, Chathambath A, Al-Sehemi AG, Pannipara M, Unnikrishnan MK, Aleya L, Raghavan RP, Mathew B. Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:38657-38672. [PMID: 35258738 PMCID: PMC8902850 DOI: 10.1007/s11356-022-19148-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 02/06/2022] [Indexed: 05/06/2023]
Abstract
COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.
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Affiliation(s)
- Rajalakshmi Rajendran
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Anjana Chathambath
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Abdullah G Al-Sehemi
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | - Mehboobali Pannipara
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | | | - Lotfi Aleya
- Laboratoire Chrono-Environment, Universite de Bourgogne Franche-Comte, CNRS6249, Besancon, France
| | - Roshni Pushpa Raghavan
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India.
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, 682 041, India
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Yang S, Tong Y, Chen L, Yu W. Human Identical Sequences, hyaluronan, and hymecromone ─ the new mechanism and management of COVID-19. MOLECULAR BIOMEDICINE 2022; 3:15. [PMID: 35593963 PMCID: PMC9120813 DOI: 10.1186/s43556-022-00077-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 05/04/2022] [Indexed: 02/08/2023] Open
Abstract
COVID-19 caused by SARS-CoV-2 has created formidable damage to public health and market economy. Currently, SARS-CoV-2 variants has exacerbated the transmission from person-to-person. Even after a great deal of investigation on COVID-19, SARS-CoV-2 is still rampaging globally, emphasizing the urgent need to reformulate effective prevention and treatment strategies. Here, we review the latest research progress of COVID-19 and provide distinct perspectives on the mechanism and management of COVID-19. Specially, we highlight the significance of Human Identical Sequences (HIS), hyaluronan, and hymecromone ("Three-H") for the understanding and intervention of COVID-19. Firstly, HIS activate inflammation-related genes to influence COVID-19 progress through NamiRNA-Enhancer network. Accumulation of hyaluronan induced by HIS-mediated HAS2 upregulation is a substantial basis for clinical manifestations of COVID-19, especially in lymphocytopenia and pulmonary ground-glass opacity. Secondly, detection of plasma hyaluronan can be effective for evaluating the progression and severity of COVID-19. Thirdly, spike glycoprotein of SARS-CoV-2 may bind to hyaluronan and further serve as an allergen to stimulate allergic reaction, causing sudden adverse effects after vaccination or the aggravation of COVID-19. Finally, antisense oligonucleotides of HIS or inhibitors of hyaluronan synthesis (hymecromone) or antiallergic agents could be promising therapeutic agents for COVID-19. Collectively, Three-H could hold the key to understand the pathogenic mechanism and create effective therapeutic strategies for COVID-19.
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Affiliation(s)
- Shuai Yang
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Ying Tong
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Lu Chen
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China
| | - Wenqiang Yu
- Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences & Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
- Shanghai Key Laboratory of Medical Epigenetics, Shanghai, 200032, People's Republic of China.
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