|
1
|
AbdelGhany Morsy SA, Abd El Mottelib LMMA, Assem S, Abd El Aziz MM, Elgeziry AH. Pioglitazone mitigates acetic acid-induced colitis in rats via epigenetic-modulation and antioxidant mechanisms. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04109-8. [PMID: 40237797 DOI: 10.1007/s00210-025-04109-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Accepted: 03/25/2025] [Indexed: 04/18/2025]
Abstract
Ulcerative colitis (UC) is one of the inflammatory bowel diseases characterized by colonic damage. Epigenetic mechanisms are suggested to play a role in the pathogenesis of UC. Pioglitazone has shown promise for the treatment of UC; however, the role of epigenetic pathways in this effect is unclear. The current study aimed to explore the therapeutic and protective effects of pioglitazone against acetic acid-induced colitis (AA-C) in rats and the role of epigenetic modulation and antioxidant mechanisms in this effect. Forty male albino rats were divided into four groups (n = 10/group): control (normal saline), acetic-acid-induced ulcerative colitis (AA-C) (3 days, 2 ml acetic acid 4%), pioglitazone-treated (AA, followed by 3-week oral pioglitazone 25 mg/kg/day), and pioglitazone-protected groups (3-day oral pioglitazone 25 mg/kg/day before AA, continued with AA, and 3 weeks later). After the experiment, the body weight, colon weight-to-length ratio, and colonic tissue were evaluated. The colonic expression of epigenetic markers (DNA methyltransferase- 1 and methylated E-cadherin), oxidative stress marker (malondialdehyde), antioxidant enzyme (superoxide dismutase), and angiotensin-converting enzyme- 2 (ACE- 2) was evaluated. The pioglitazone-protected and treated groups showed significant inhibition of DNA methyltransferase- 1 and methylated E-cadherin with improvement in colonic tissue macroscopic and microscopic signs of inflammation, improved weight, less oxidative stress, and less ACE- 2 expression. These beneficial actions were more pronounced among the pioglitazone-protected group. Pioglitazone could mitigate AA-C in rats by inhibiting epigenetic DNA methyltransferase- 1 and E-cadherin gene methylation. It also inhibits oxidative stress and prevents the overexpression of ACE- 2.
Collapse
Affiliation(s)
- Suzan Awad AbdelGhany Morsy
- Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt.
- Pathological Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, 21461, Jeddah, Saudi Arabia.
| | - Lobna M M A Abd El Mottelib
- Department of Human Anatomy and Embryology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt
| | - Sara Assem
- Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt
| | - M M Abd El Aziz
- Department of Pathology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt
| | - Anne H Elgeziry
- Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Dr. Fahmi Abdelmeguid St., Mowassah Campus, Alexandria, 21561, Egypt
| |
Collapse
|
|
2
|
Serrano-Arroyo L, González-Meléndez A, Ríos-Rivera R, Rodríguez-González V, Vilá LM. Impact of SARS-CoV-2 pre-delta/delta and omicron variants on clinical outcomes in a systemic lupus erythematosus cohort from Puerto Rico. Lupus 2025; 34:415-424. [PMID: 40015557 DOI: 10.1177/09612033251325361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
ObjectiveTo examine the clinical outcomes of systemic lupus erythematosus (SLE) patients with COVID-19 during the Pre-Delta/Delta and Omicron periods.MethodsA retrospective study was conducted in a cohort of adult Puerto Ricans with SLE. Demographic parameters, SLE and COVID-19 manifestations, comorbidities, pharmacologic treatment, SLE exacerbations, hospitalizations, and mortality were determined. SARS CoV-2 infection was confirmed by polymerase chain reaction or antigen tests. Variables were compared between the Pre-delta/Delta and Omicron periods. Also, the proportion of COVID-19 cases and mortality of SLE patients was compared to the general population of Puerto Rico.ResultsOf the entire SLE cohort (n = 347), 169 patients (48.7%) had COVID-19. Twenty-two patients had COVID-19 during the Pre-delta/Delta period and 147 during the Omicron period. The proportion of COVID-19 cases in the SLE cohort was significantly higher when compared to the adult general population of Puerto Rico (25.7%), but no difference in mortality was found. Overall, the clinical outcomes of COVID-19 in the SLE cohort were favorable, with low rates of lupus flares (3.0%), hospitalizations (3.6%), and mortality (0.6%). Patients with COVID-19 during the Pre-delta/Delta period were more likely to have oral ulcers, anti-Smith antibodies, and chronic kidney disease, whereas those during the Omicron period were more likely to have COVID-19 symptoms (rhinorrhea, sore throat, and cough).ConclusionIn summary, is this group of Puerto Ricans with SLE, a high proportion had COVID-19, but disease exacerbation, hospitalization, and mortality rates were low. Few clinical differences were noted in SLE patients when comparing the Pre-delta/Delta and Omicron periods.
Collapse
Affiliation(s)
- Lilliana Serrano-Arroyo
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Ariana González-Meléndez
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Rafael Ríos-Rivera
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Valeria Rodríguez-González
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Luis M Vilá
- Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| |
Collapse
|
|
3
|
Saha A, Ganguly A, Kumar A, Srivastava N, Pathak R. Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections. Pathogens 2025; 14:129. [PMID: 40005506 PMCID: PMC11858160 DOI: 10.3390/pathogens14020129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/27/2025] Open
Abstract
Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host's epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host's innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally.
Collapse
Affiliation(s)
- Ankita Saha
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; (A.S.); (N.S.)
| | - Anirban Ganguly
- Department of Biochemistry, All India Institute of Medical Sciences, Deoghar 814152, India;
| | - Anoop Kumar
- Molecular Diagnostic Laboratory, National Institute of Biologicals, Noida 201309, India;
| | - Nityanand Srivastava
- Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA; (A.S.); (N.S.)
| | - Rajiv Pathak
- Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA
| |
Collapse
|
|
4
|
Gasmi A, Kassym L, Menzel A, Anzar W, Dadar M, Semenova Y, Arshad M, Bihunyak T, Meguid NA, Peana M, Bekbergenova Z, Bjørklund G. Genetic and Epigenetic Determinants of COVID-19 Susceptibility: A Systematic Review. Curr Med Chem 2025; 32:753-770. [PMID: 38251695 DOI: 10.2174/0109298673267890231221100659] [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: 06/18/2023] [Revised: 08/04/2023] [Accepted: 11/14/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence. METHODS This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023. RESULTS The findings reveal that the host's HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication. CONCLUSION There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.
Collapse
Affiliation(s)
- Amin Gasmi
- Department of Research, Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
| | - Laura Kassym
- Department of Research, Astana Medical University, Astana, Kazakhstan
| | - Alain Menzel
- Department of Research, Laboratoires Réunis, Junglinster, Luxembourg
| | - Wajiha Anzar
- Department of Research, Dow University of Health Sciences, Karachi, Pakistan
| | - Maryam Dadar
- Department of Research, CONEM Iran Microbiology Research Group, Tehran, Iran
| | - Yuliya Semenova
- Department of Research, Nazarbayev University School of Medicine, Astana, Kazakhstan
| | - Mehreen Arshad
- Department of Research, National University of Sciences and Technology, Islamabad, Pakistan
| | - Tetyana Bihunyak
- Department of Research, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
| | - Nagwa Abdel Meguid
- Research on Children with Special Needs Department, National Research Centre, Giza, Egypt
- CONEM Egypt Child Brain Research Group, National Research Center, Giza, Egypt
| | - Massimiliano Peana
- Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Sassari, Italy
| | | | - Geir Bjørklund
- Department of Research, Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway
| |
Collapse
|
|
5
|
Hart AP, Kotzin JJ, Schulz SW, Dunham JS, Keenan AL, Baker JF, Wells AD, Beiting DP, Laufer TM. Angiotensin receptor blockers modulate the lupus CD4+ T cell epigenome characterized by TNF family-linked signaling. JCI Insight 2024; 10:e176811. [PMID: 39688922 PMCID: PMC11948580 DOI: 10.1172/jci.insight.176811] [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: 10/18/2023] [Accepted: 12/13/2024] [Indexed: 12/18/2024] Open
Abstract
In systemic lupus erythematosus (lupus), environmental effects acting within a permissive genetic background lead to autoimmune dysregulation. Dysfunction of CD4+ T cells contributes to pathology by providing help to autoreactive B and T cells, and CD4+ T cell dysfunction coincides with altered DNA methylation and histone modifications of select gene loci. However, chromatin accessibility states of distinct T cell subsets and mechanisms driving heterogeneous chromatin states across patients remain poorly understood. We defined the transcriptome and epigenome of multiple CD4+ T cell populations from patients with lupus and healthy individuals. Most patients with lupus, regardless of disease activity, had enhanced chromatin accessibility bearing hallmarks of inflammatory cytokine signals. Single-cell approaches revealed that chromatin changes extended to naive CD4+ T cells, uniformly affecting naive subpopulations. Transcriptional data and cellular and protein analyses suggested that the TNF family members, TNF-α, LIGHT, and TWEAK, were linked to observed molecular changes and the altered lupus chromatin state. However, we identified a patient subgroup prescribed angiotensin receptor blockers (ARBs), which lacked TNF-linked lupus chromatin accessibility features. These data raise questions about the role of lupus-associated chromatin changes in naive CD4+ T cell activation and differentiation and implicate ARBs in the regulation of disease-driven epigenetic states.
Collapse
Affiliation(s)
- Andrew P. Hart
- Division of Rheumatology, Department of Medicine, and
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Jonathan J. Kotzin
- Division of Rheumatology, Department of Medicine, and
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | | | | | - Joshua F. Baker
- Division of Rheumatology, Department of Medicine, and
- Division of Rheumatology, Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
- Center for Clinical Epidemiology and Biostatistics and
| | - Andrew D. Wells
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Pathology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Daniel P. Beiting
- Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Terri M. Laufer
- Division of Rheumatology, Department of Medicine, and
- Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Division of Rheumatology, Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
6
|
Alie MS, Girma D, Negesse Y, Adugna A, Abebe GF. Impact of COVID-19 on individual mental health and maternal health services in Ethiopia: systematic review and meta-analysis. Front Public Health 2024; 12:1407269. [PMID: 38979045 PMCID: PMC11228260 DOI: 10.3389/fpubh.2024.1407269] [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: 04/03/2024] [Accepted: 05/23/2024] [Indexed: 07/10/2024] Open
Abstract
Background The COVID-19 pandemic has caused a major outbreak in the 21st century and has led to significant mental health hazards worldwide. To address this issue, a systematic review has been conducted to analyze existing literature on the impact of COVID-19 on the psychological well-being of the general population, as well as the associated risk factors. Methods A comprehensive search was carried out on PubMed, Embase, Medline, Web of Science, and Scopus databases, covering all available literature up until February 20, 2024. This search was conducted in accordance with the PRISMA guidelines, ensuring a systematic approach. The selection of articles was based on predetermined eligibility criteria, ensuring the inclusion of appropriate and suitable research. In the final analysis, a total of 15 articles focusing on depression and anxiety, 11 articles on stress, and 7 articles on psychological problems were included. These articles specifically examined the outcome variables within the context of English language and specific areas. For the meta-analysis on maternal health services, 11 articles were included for family planning, 25 articles for postnatal care services, 16 articles for institutional delivery, and 14 articles for safe abortion services. These articles were carefully selected for the final pooled analysis. Result According to a recent systematic review, anxiety, depression, stress, and psychological distress have been prevalent in Ethiopia during the COVID-19 pandemic, with rates of 40, 41, 23, and 41%, respectively. The review also identified various sociodemographic factors that have impacted the country's response to the pandemic, including female gender, age, marital status, incarceration, low income, and lack of social support. Furthermore, the review found that maternal health services have experienced significant reductions during the pandemic. Conclusion The COVID-19 pandemic has led to a significant increase in psychological distress, which in some cases, is severe enough to require clinical treatment. It is crucial to prioritize efforts to address the negative impact of COVID-19 on mental health as a global public health priority. Additionally, it is important to pay attention to maternal health services during COVID-19 mitigation programs.
Collapse
Affiliation(s)
- Melsew Setegn Alie
- Department of Public Health, School of Public Health, College of Medicine and Health Science, Mizan-Tepi University, Mizan-Aman, Ethiopia
| | - Desalegn Girma
- Department of Midwifery, College of Medicine and Health Science, Mizan-Tepi University, Mizan-Aman, Ethiopia
| | - Yilkal Negesse
- Department of Public Health, College of Medicine and Health Science, Debre Markos University, Debre Markos, Gojjam, Ethiopia
| | - Amanuel Adugna
- Department of Midwifery, College of Medicine and Health Science, Mizan-Tepi University, Mizan-Aman, Ethiopia
| | - Gossa Fetene Abebe
- Department of Midwifery, College of Medicine and Health Science, Mizan-Tepi University, Mizan-Aman, Ethiopia
| |
Collapse
|
|
7
|
Bai A, Li J, Pan Y, Jiang Y. Suicide in Hong Kong during the COVID-19 pandemic: an observational study. BMJ PUBLIC HEALTH 2024; 2:e001125. [PMID: 40018162 PMCID: PMC11812919 DOI: 10.1136/bmjph-2024-001125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/29/2024] [Indexed: 03/01/2025]
Abstract
Introduction The COVID-19 pandemic has exacerbated suicide risk factors in Hong Kong, which faces economic shocks and strict travel restrictions due to its unique economic structure and geographical location. However, there is a scarcity of reliable empirical evidence regarding the relationship between the pandemic and suicide mortality. This study examines whether changes in the suicide rate align with COVID-19 situations and anti-COVID-19 policy events in Hong Kong, focusing on vulnerable population groups based on demographic and socioeconomic characteristics. Methods Suicide data spanning 1 January 2019 to 31 December 2022 were sourced from the Hong Kong Suicide Press Database. Case-level data were aggregated monthly by district. Population-weighted Poisson regression with district-level fixed effects was employed to analyse suicide patterns and their association with COVID-19 developments. Robustness checks and demographic-based heterogeneity analysis were conducted, distinguishing suicide risk among different population groups. Results A total of 4061 suicide cases were analysed, encompassing deaths and attempts. The first wave of the pandemic saw a 30% decline in suicide cases compared with the 2019 average, while the second and fifth waves witnessed increases of 33% and 51% in suicide rates, respectively. Older adults and individuals with lower socioeconomic status were particularly susceptible to the adverse effects, as evidenced by a significant rise in suicides during the fifth wave. Conclusions The findings underscore the importance of targeted interventions to address the mental health needs of vulnerable populations during pandemics, highlighting the impact of COVID-19 situations and antipandemic policies on the suicide rate.
Collapse
Affiliation(s)
- Anying Bai
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Jinjian Li
- The Hong Kong University of Science and Technology, Hong Kong, Hong Kong SAR
| | - Yuhang Pan
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Yu Jiang
- School of Health Policy and Management, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China
| |
Collapse
|
|
8
|
Han L, Cao F, Zhang Y, Su M, Wu Y, Li C. SAPHO syndrome after COVID-19 vaccination. Int J Rheum Dis 2024; 27:e15221. [PMID: 38874318 DOI: 10.1111/1756-185x.15221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 05/30/2024] [Indexed: 06/15/2024]
Affiliation(s)
- Luyao Han
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Fengjiao Cao
- Department of Rheumatology, Dongfang Hospital Beijing University of Chinese Medicine, Beijing, China
| | - Yuru Zhang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Minhui Su
- Department of Rheumatology, Changzhou Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Jiangsu Province, China
| | - Yuanhao Wu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chen Li
- Department of Rheumatology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
|
9
|
Meshref M, Ghaith HS, Hammad MA, Shalaby MMM, Ayasra F, Monib FA, Attia MS, Ebada MA, Elsayed H, Shalash A, Bahbah EI. The Role of RIN3 Gene in Alzheimer's Disease Pathogenesis: a Comprehensive Review. Mol Neurobiol 2024; 61:3528-3544. [PMID: 37995081 PMCID: PMC11087354 DOI: 10.1007/s12035-023-03802-0] [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: 09/08/2023] [Accepted: 11/10/2023] [Indexed: 11/24/2023]
Abstract
Alzheimer's disease (AD) is a globally prevalent form of dementia that impacts diverse populations and is characterized by progressive neurodegeneration and impairments in executive memory. Although the exact mechanisms underlying AD pathogenesis remain unclear, it is commonly accepted that the aggregation of misfolded proteins, such as amyloid plaques and neurofibrillary tau tangles, plays a critical role. Additionally, AD is a multifactorial condition influenced by various genetic factors and can manifest as either early-onset AD (EOAD) or late-onset AD (LOAD), each associated with specific gene variants. One gene of particular interest in both EOAD and LOAD is RIN3, a guanine nucleotide exchange factor. This gene plays a multifaceted role in AD pathogenesis. Firstly, upregulation of RIN3 can result in endosomal enlargement and dysfunction, thereby facilitating the accumulation of beta-amyloid (Aβ) peptides in the brain. Secondly, RIN3 has been shown to impact the PICLAM pathway, affecting transcytosis across the blood-brain barrier. Lastly, RIN3 has implications for immune-mediated responses, notably through its influence on the PTK2B gene. This review aims to provide a concise overview of AD and delve into the role of the RIN3 gene in its pathogenesis.
Collapse
Affiliation(s)
- Mostafa Meshref
- Department of Neurology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | | | | | | | - Faris Ayasra
- Faculty of Medicine, The Hashemite University, Zarqa, Jordan
| | | | - Mohamed S Attia
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | | | - Hanaa Elsayed
- Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ali Shalash
- Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Eshak I Bahbah
- Faculty of Medicine, Al-Azhar University, Damietta, Egypt.
| |
Collapse
|
|
10
|
Zhao X, Wu H, Li S, Gao C, Wang J, Ge L, Song Z, Ni B, You Y. The impact of the COVID-19 pandemic on SLE. Mod Rheumatol 2024; 34:247-264. [PMID: 36961736 DOI: 10.1093/mr/road030] [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: 12/13/2022] [Revised: 02/21/2023] [Accepted: 03/11/2023] [Indexed: 03/25/2023]
Abstract
Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.
Collapse
Affiliation(s)
- Xingwang Zhao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Haohao Wu
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shifei Li
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Cuie Gao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Juan Wang
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lan Ge
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhiqiang Song
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Bing Ni
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yi You
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| |
Collapse
|
|
11
|
Asteris PG, Gandomi AH, Armaghani DJ, Tsoukalas MZ, Gavriilaki E, Gerber G, Konstantakatos G, Skentou AD, Triantafyllidis L, Kotsiou N, Braunstein E, Chen H, Brodsky R, Touloumenidou T, Sakellari I, Alkayem NF, Bardhan A, Cao M, Cavaleri L, Formisano A, Guney D, Hasanipanah M, Khandelwal M, Mohammed AS, Samui P, Zhou J, Terpos E, Dimopoulos MA. Genetic justification of COVID-19 patient outcomes using DERGA, a novel data ensemble refinement greedy algorithm. J Cell Mol Med 2024; 28:e18105. [PMID: 38339761 PMCID: PMC10863978 DOI: 10.1111/jcmm.18105] [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: 06/12/2023] [Revised: 11/14/2023] [Accepted: 11/22/2023] [Indexed: 02/12/2024] Open
Abstract
Complement inhibition has shown promise in various disorders, including COVID-19. A prediction tool including complement genetic variants is vital. This study aims to identify crucial complement-related variants and determine an optimal pattern for accurate disease outcome prediction. Genetic data from 204 COVID-19 patients hospitalized between April 2020 and April 2021 at three referral centres were analysed using an artificial intelligence-based algorithm to predict disease outcome (ICU vs. non-ICU admission). A recently introduced alpha-index identified the 30 most predictive genetic variants. DERGA algorithm, which employs multiple classification algorithms, determined the optimal pattern of these key variants, resulting in 97% accuracy for predicting disease outcome. Individual variations ranged from 40 to 161 variants per patient, with 977 total variants detected. This study demonstrates the utility of alpha-index in ranking a substantial number of genetic variants. This approach enables the implementation of well-established classification algorithms that effectively determine the relevance of genetic variants in predicting outcomes with high accuracy.
Collapse
Affiliation(s)
- Panagiotis G. Asteris
- Computational Mechanics Laboratory, School of Pedagogical and Technological EducationAthensGreece
| | - Amir H. Gandomi
- Faculty of Engineering & ITUniversity of Technology SydneySydneyNew South WalesAustralia
- University Research and Innovation Center (EKIK), Óbuda UniversityBudapestHungary
| | - Danial J. Armaghani
- School of Civil and Environmental EngineeringUniversity of Technology SydneySydneyNew South WalesAustralia
| | - Markos Z. Tsoukalas
- Computational Mechanics Laboratory, School of Pedagogical and Technological EducationAthensGreece
| | - Eleni Gavriilaki
- 2nd Propedeutic Department of Internal MedicineAristotle University of ThessalonikiThessalonikiGreece
| | - Gloria Gerber
- Hematology DivisionJohns Hopkins UniversityBaltimoreUSA
| | - Gerasimos Konstantakatos
- Computational Mechanics Laboratory, School of Pedagogical and Technological EducationAthensGreece
| | - Athanasia D. Skentou
- Computational Mechanics Laboratory, School of Pedagogical and Technological EducationAthensGreece
| | - Leonidas Triantafyllidis
- Computational Mechanics Laboratory, School of Pedagogical and Technological EducationAthensGreece
| | - Nikolaos Kotsiou
- 2nd Propedeutic Department of Internal MedicineAristotle University of ThessalonikiThessalonikiGreece
| | | | - Hang Chen
- Hematology DivisionJohns Hopkins UniversityBaltimoreUSA
| | | | | | - Ioanna Sakellari
- Hematology Department – BMT UnitG Papanicolaou HospitalThessalonikiGreece
| | | | - Abidhan Bardhan
- Civil Engineering DepartmentNational Institute of Technology PatnaPatnaIndia
| | - Maosen Cao
- Department of Engineering MechanicsHohai UniversityNanjingChina
| | - Liborio Cavaleri
- Department of Civil, Environmental, Aerospace and Materials EngineeringUniversity of PalermoPalermoItaly
| | - Antonio Formisano
- Department of Structures for Engineering and ArchitectureUniversity of Naples “Federico II”NaplesItaly
| | - Deniz Guney
- Engineering FacultySan Diego State UniversitySan DiegoCaliforniaUSA
| | - Mahdi Hasanipanah
- Department of Geotechnics and Transportation, Faculty of Civil EngineeringUniversiti Teknologi MalaysiaJohor BahruMalaysia
| | - Manoj Khandelwal
- Institute of Innovation, Science and SustainabilityFederation University AustraliaBallaratVictoriaAustralia
| | | | - Pijush Samui
- Civil Engineering DepartmentNational Institute of Technology PatnaPatnaIndia
| | - Jian Zhou
- School of Resources and Safety EngineeringCentral South UniversityChangshaChina
| | - Evangelos Terpos
- Department of Clinical Therapeutics, Medical School, Faculty of MedicineNational Kapodistrian University of AthensAthensGreece
| | - Meletios A. Dimopoulos
- Department of Clinical Therapeutics, Medical School, Faculty of MedicineNational Kapodistrian University of AthensAthensGreece
| |
Collapse
|
|
12
|
Bavarsad K, Shalil Ahmadi D, Momeni M, Yadyad MJ, Salehi Kahyesh R, Moradzadegan H, Ghafouri S. Evaluation of the relationship between serum BDNF concentration and indicators of oxidative stress and inflammation in COVID-19 patients with neurological disorders - a pilot study. Neurol Res 2024; 46:33-41. [PMID: 37706246 DOI: 10.1080/01616412.2023.2257448] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 07/30/2023] [Indexed: 09/15/2023]
Abstract
INTRODUCTION The aim of this study was to determine the effect of serum level of brain-derived neurotrophic factor (BDNF) on the development of neurological disorders in COVID-19 patients and the probable role of oxidative stress and inflammation in this phenomenon. METHODS The present case-control study included 42 COVID-19 patients referring to Golestan and Sina hospitals of Ahvaz, Iran, for treatment. Patients with (n = 18) and without (n = 24) neurological disorders were allocated into test and control groups, respectively. Following blood sampling, serum isolation was done, and the serum was stored at -80°C until biochemical assessment for measuring BDNF, oxidative stress indices, and inflammatory factors. RESULTS Although no significant brain damage was observed in the COVID-19 patients with neurological disorders, the results showed that the serum level of BDNF in the test group increased compared to that in the control group, and this increment was accompanied with increased Tumor Necrosis Factor-alpha (TNF-α) and decreased Interferon gamma (IFN-γ) levels in the serum. Moreover, compared to the control group, patients in the test group had a decreased level of Thiol and an increased level of Malondialdehyde (MDA) in the serum. Furthermore, there was a significant positive correlation between the serum concentration of BDNF and nitric oxide (NO) in the test group. CONCLUSION Using over-the-counter (OTC) medicines which include thiol-group-related agents or any other antioxidants can alleviate oxidative stress and the associated increased inflammation in COVID-19 patients with neurological symptoms.
Collapse
Affiliation(s)
- Kowsar Bavarsad
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Davood Shalil Ahmadi
- Department of Neurology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Momeni
- Advanced Diagnostic and Interventional Radiology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Jafar Yadyad
- Department of Infection Disease, Sina Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Roya Salehi Kahyesh
- Thalasemia and Hemoglobinopathy Research Center, Research Institute of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Samireh Ghafouri
- Department of Physiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Persian Gulf Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| |
Collapse
|
|
13
|
Dey A, Vaishak K, Deka D, Radhakrishnan AK, Paul S, Shanmugam P, Daniel AP, Pathak S, Duttaroy AK, Banerjee A. Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review. Infection 2023; 51:1603-1618. [PMID: 36906872 PMCID: PMC10008189 DOI: 10.1007/s15010-023-02017-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 02/27/2023] [Indexed: 03/13/2023]
Abstract
PURPOSE The COVID-19 pandemic caused by the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has put the world in a medical crisis for the past three years; nearly 6.3 million lives have been diminished due to the virus outbreak. This review aims to update the recent findings on COVID-19 infections from an epigenetic scenario and develop future perspectives of epi-drugs to treat the disease. METHODS Original research articles and review studies related to COVID-19 were searched and analyzed from the Google Scholar/PubMed/Medline databases mainly between 2019 and 2022 to brief the recent work. RESULTS Numerous in-depth studies of the mechanisms used by SARS-CoV-2 have been going on to minimize the consequences of the viral outburst. Angiotensin-Converting Enzyme 2 receptors and Transmembrane serine protease 2 facilitate viral entry to the host cells. Upon internalization, it uses the host machinery to replicate viral copies and alter the downstream regulation of the normal cells, causing infection-related morbidities and mortalities. In addition, several epigenetic regulations such as DNA methylation, acetylation, histone modifications, microRNA, and other factors (age, sex, etc.) are responsible for the regulations of viral entry, its immune evasion, and cytokine responses also play a major modulatory role in COVID-19 severity, which has been discussed in detail in this review. CONCLUSION Findings of epigenetic regulation of viral pathogenicity open a new window for epi-drugs as a possible therapeutical approach against COVID-19.
Collapse
Affiliation(s)
- Amit Dey
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, TN, 603103, India
| | - K Vaishak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, TN, 603103, India
| | - Dikshita Deka
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, TN, 603103, India
| | - Arun Kumar Radhakrishnan
- Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, TN, India
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No.500 Fracc., CP 76130, San Pablo, Querétaro, Mexico
| | - Priyadarshini Shanmugam
- Department of Microbiology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, TN, 603103, India
| | - Alice Peace Daniel
- Department of Microbiology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, TN, 603103, India
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, TN, 603103, India
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Antara Banerjee
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Chennai, TN, 603103, India.
| |
Collapse
|
|
14
|
Saksena NK, Reddy SB, Miranda-Saksena M, Cardoso THS, Silva EMA, Ferreira JC, Rabeh WM. SARS-CoV-2 variants, its recombinants and epigenomic exploitation of host defenses. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166836. [PMID: 37549720 DOI: 10.1016/j.bbadis.2023.166836] [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: 01/30/2023] [Revised: 07/17/2023] [Accepted: 07/31/2023] [Indexed: 08/09/2023]
Abstract
Since 2003, we have seen the emergence of novel viruses, such as SARS-CoV-1, MERS, ZIKA, swine flu virus H1N1, Marburg, Monkeypox, Ebola, and SARS-CoV-2, but none of them gained pandemic proportions similar to SARS-CoV-2. This could be attributed to unique viral traits, allowing its rapid global dissemination following its emergence in October 2019 in Wuhan, China, which appears to be primarily driven by the emergence of highly transmissible and virulent variants that also associate, in some cases, with severe disease and considerable mortality caused by fatal pneumonia, acute respiratory distress syndrome (ARDS) in infected individuals. Mechanistically, several factors are involved in viral pathogenesis, and epigenetic alterations take the front seat in host-virus interactions. The molecular basis of all viral infections, including SARS-CoV-2, tightly hinges on the transitory silencing of the host gene machinery via epigenetic modulation. SARS-CoV-2 also hijacks and subdues the host gene machinery, leading to epigenetic modulation of the critical host elements responsible for antiviral immunity. Epigenomics is a powerful, unexplored avenue that can provide a profound understanding of virus-host interactions and lead to the development of epigenome-based therapies and vaccines to counter viruses. This review discusses current developments in SARS-CoV-2 variation and its role in epigenetic modulation in infected hosts. This review provides an overview, especially in the context of emerging viral strains, their recombinants, and their possible roles in the epigenetic exploitation of host defense and viral pathogenesis. It provides insights into host-virus interactions at the molecular, genomic, and immunological levels and sheds light on the future of epigenomics-based therapies for SARS-CoV-2 infection.
Collapse
Affiliation(s)
- Nitin K Saksena
- Victoria University, Footscray Campus, Melbourne, VIC. Australia.
| | - Srinivasa Bonam Reddy
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
| | | | - Thyago H S Cardoso
- OMICS Centre of Excellence, G42 Healthcare, Mazdar City, Abu Dhabi, United Arab Emirates.
| | - Edson M A Silva
- Science Division, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Juliana C Ferreira
- Science Division, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates.
| | - Wael M Rabeh
- Science Division, New York University Abu Dhabi, PO Box 129188, Abu Dhabi, United Arab Emirates.
| |
Collapse
|
|
15
|
Primo MGS, da Silva LAA, de Carvalho VBL, de Azevedo MAF, Monteiro NVDN, Mendes VR, da Silva JKM, Oliveira ASDSS, Brito AKDS, Sales ALDCC, Mallet JRDS, Parente JML, de Matos Neto EM, Ferreira PMP, Arcanjo DDR, Martins MDCDCE. Relationship among Dietary Intake of Vitamin E, Lipid Peroxidation Markers, and C-Reactive Protein in Flu-Like Patients Diagnosed with COVID-19. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:8889213. [PMID: 39263681 PMCID: PMC11390186 DOI: 10.1155/2023/8889213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 07/05/2023] [Accepted: 09/30/2023] [Indexed: 09/13/2024]
Abstract
Objective This research aimed to assess the intake of vitamin E and its relationship with lipid peroxidation markers and C-reactive protein levels in patients with flu symptoms and COVID-19 diagnosis. Methods A cross-sectional study with 121 patients of both sexes assisted at two basic health units in the city of Teresina, Piauí, with COVID-19 diagnosis confirmed through real-time reverse transcription polymerase chain reaction, was performed between the 3rd and 7th days of flu symptoms. The global nutritional status and the measurement of waist circumference were assessed according to the World Health Organization recommendations. The dietary energy intake, macronutrients, and vitamin E consumption were assessed through the 24 hr food recall method. The malondialdehyde plasmatic concentration (MDA) was measured through the method of thiobarbituric acid-reactive substances. Myeloperoxidase (MPO) was assessed through the oxidation speed of the o-dianisidine substrate in the presence of hydrogen peroxide. C-reactive protein (CRP) levels were measured by a high-sensitivity immunoturbidimetry method. Results The most common symptoms reported by the participants were sore throat, fever, and cough. Regarding the global nutritional status evaluation, the majority of the sample had overweight. The dietary intake of vitamin E was 100% inadequate and presented a mild correlation (r = 0.197) with MDA, a redox status marker. No correlation was observed among MPO, CRP, and the dietary intake of vitamin E. Conclusion The dietary intake of vitamin E was related to MDA as the marker of redox status.
Collapse
|
|
16
|
Napoli C, Coscioni E, Trama U, Strozziero MG, Benincasa G. An evidence-based debate on epigenetics and immunosenescence in COVID-19. CURRENT RESEARCH IN IMMUNOLOGY 2023; 4:100069. [PMID: 37781451 PMCID: PMC10539895 DOI: 10.1016/j.crimmu.2023.100069] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/01/2023] [Accepted: 09/06/2023] [Indexed: 10/03/2023] Open
Abstract
Immunosenescence contributes to the decline of immune function leading to a reduced ability to respond to severe coronavirus disease 2019 (COVID-19) in elderly patients. Clinical course of COVID-19 is widely heterogeneous and guided by the possible interplay between genetic background and epigenetic-sensitive mechanisms underlying the immunosenescence which could explain, at least in part, the higher percentage of disease severity in elderly individuals. The most convincing evidence regards the hypomethylation of the angiotensin-converting enzyme 2 (ACE2) promoter gene in lungs as well as the citrullination of histone H3 in neutrophils which have been associated with worsening of COVID-19 outcome in elderly patients. In contrast, centenarians who have showed milder symptoms have been associated to a younger "epigenetic age" based on DNA methylation profiles at specific genomic sites (epigenetic clock). Some large prospective studies showed that the acceleration of epigenetic aging as well as the shortening of telomeres were significantly associated with lymphopenia and poor outcome suggesting prognostic biomarkers in elderly COVID-19 patients. Furthermore, randomized clinical trials showed that statins, L-arginine, and resveratrol could mediate anti-inflammatory effects via indirect epigenetic interference and might improve COVID-19 outcome. Here, we discuss the epigenetic-sensitive events which might contribute to increase the risk of severity and mortality in older subjects and possible targeted therapies to counteract immunosenescence.
Collapse
Affiliation(s)
- Claudio Napoli
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy
- U.O.C. Division of Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, Department of Internal Medicine and Specialistics, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Enrico Coscioni
- Division of Cardiac Surgery, AOU San Giovanni di Dio e Ruggid'Aragona, 84131, Salerno, Italy
| | - Ugo Trama
- Regional Pharmaceutical Unit, Campania Region, 80143 Naples, Italy
| | - Maria Grazia Strozziero
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy
- IRCCS Synlab SDN Naples Italy
| | - Giuditta Benincasa
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, Italy
| |
Collapse
|
|
17
|
Zhao X, Zhang M, Jia Y, Liu W, Li S, Gao C, Zhang L, Ni B, Ruan Z, Dong R. Featured immune characteristics of COVID-19 and systemic lupus erythematosus revealed by multidimensional integrated analyses. Inflamm Res 2023; 72:1877-1894. [PMID: 37725104 DOI: 10.1007/s00011-023-01791-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 08/16/2023] [Accepted: 08/19/2023] [Indexed: 09/21/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) shares similar immune characteristics with autoimmune diseases like systemic lupus erythematosus (SLE). However, such associations have not yet been investigated at the single-cell level. METHODS We integrated and analyzed RNA sequencing results from different patients and normal controls from the GEO database and identified subsets of immune cells that might involve in the pathogenesis of SLE and COVID- 19. We also disentangled the characteristic alterations in cell and molecular subset proportions as well as gene expression patterns in SLE patients compared with COVID-19 patients. RESULTS Key immune characteristic genes (such as CXCL10 and RACK1) and multiple immune-related pathways (such as the coronavirus disease-COVID-19, T-cell receptor signaling, and MIF-related signaling pathways) were identified. We also highlighted the differences in peripheral blood mononuclear cells (PBMCs) between SLE and COVID-19 patients. Moreover, we provided an opportunity to comprehensively probe underlying B-cell‒cell communication with multiple ligand-receptor pairs (MIF-CD74+CXCR4, MIF-CD74+CD44) and the differentiation trajectory of B-cell clusters that is deemed to promote cell state transitions in COVID-19 and SLE. CONCLUSIONS Our results demonstrate the immune response differences and immune characteristic similarities, such as the cytokine storm, between COVID-19 and SLE, which might pivotally function in the pathogenesis of the two diseases and provide potential intervention targets for both diseases.
Collapse
Affiliation(s)
- Xingwang Zhao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Mengjie Zhang
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Yuying Jia
- Department of Dermatology, The 901th Hospital of the Joint Logistics Support Force of PLA, Affiliated to Anhui Medical University, Hefei, Anhui, China
- Division of Life Sciences and Medicine, Dermatology Department of the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230001, Anhui, People's Republic of China
| | - Wenying Liu
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Shifei Li
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Cuie Gao
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Lian Zhang
- Department of Dermatology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Bing Ni
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China
| | - Zhihua Ruan
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
| | - Rui Dong
- Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.
- Chongqing International Institute for Immunology, Chongqing, 401320, China.
| |
Collapse
|
|
18
|
Wanjari M, Late S, Sharma R, Munjewar P. Long-term pulmonary and extra-pulmonary consequences of COVID-19: A comprehensive review of current evidence and future perspectives. NARRA J 2023; 3:e156. [PMID: 38454970 PMCID: PMC10919748 DOI: 10.52225/narra.v3i2.156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/26/2023] [Indexed: 03/09/2024]
Abstract
The global impact of the coronavirus disease 2019 (COVID-19) pandemic has been significant, affecting countless individuals worldwide. The existence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to considerable levels of illness and mortality. While considerable attention has been devoted to the immediate handling of COVID-19, there is a growing concern about the long-term effects of this disease. The recent studies have brought to light various complexities associated with COVID-19, encompassing both respiratory and non-respiratory problems such as lung scarring, heart diseases, neurological effects, and psychological consequences. The purpose of this review is to provide a comprehensive understanding of the persistent repercussions of COVID-19. It presents a summary of recent studies that have examined the frequency and severity of these complications, as well as an exploration of the potential mechanisms that contribute to their development. Specifically, it delves into the role of immune dysregulation, prolonged inflammation, and dysfunction of blood vessel linings in the origin of these complications. Moreover, the clinical significance of these long-term consequences is discussed, including their potential impact on healthcare systems and society as a whole. Our review highlights the necessity for continuous monitoring and management of patients diagnosed with COVID-19, along with the importance of conducting follow-up studies over an extended period to determine the most effective strategies for prevention and treatment of these complications.
Collapse
Affiliation(s)
- Mayur Wanjari
- Departement of Research and Development, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, India
| | - Sampada Late
- Department of Nursing, Government Hospital Samudrapur, Wardha, India
| | - Ranjana Sharma
- Department of Medical Surgical Nursing, Srimati Radhikabai Meghe Memorial College of Nursing, Datta Meghe Institute of Higher Education & Research, Wardha, India
| | - Pratiksha Munjewar
- Department of Medical Surgical Nursing, Srimati Radhikabai Meghe Memorial College of Nursing, Datta Meghe Institute of Higher Education & Research, Wardha, India
| |
Collapse
|
|
19
|
Akhil A, Bansal R, Anupam K, Tandon A, Bhatnagar A. Systemic lupus erythematosus: latest insight into etiopathogenesis. Rheumatol Int 2023:10.1007/s00296-023-05346-x. [PMID: 37226016 DOI: 10.1007/s00296-023-05346-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 05/15/2023] [Indexed: 05/26/2023]
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.
Collapse
Affiliation(s)
- Akhil Akhil
- Department of Biochemistry, BMS-Block II, South Campus, Panjab University, Chandigarh, 160014, India
| | - Rohit Bansal
- Department of Biochemistry, BMS-Block II, South Campus, Panjab University, Chandigarh, 160014, India
| | - Kumari Anupam
- Department of Pathology, Saint Louis University, St. Louis, MO, 63103, USA
| | - Ankit Tandon
- Department of Endocrinology, PGIMER, Chandigarh, 160012, India
| | - Archana Bhatnagar
- Department of Biochemistry, BMS-Block II, South Campus, Panjab University, Chandigarh, 160014, India.
| |
Collapse
|
|
20
|
Xu SZ, Wang ZX, Fang X, Chen C, Yang XK, Shuai ZW, Tao SS. No genetic causal association between systemic lupus erythematosus and COVID-19. Front Immunol 2023; 14:1183570. [PMID: 37275906 PMCID: PMC10232808 DOI: 10.3389/fimmu.2023.1183570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/02/2023] [Indexed: 06/07/2023] Open
Abstract
Objective Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.
Collapse
Affiliation(s)
- Shu-Zhen Xu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zhi-Xin Wang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xi Fang
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Cong Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Xiao-Ke Yang
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Zong-Wen Shuai
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Sha-Sha Tao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Institute of Kidney Disease, Inflammation and Immunity Mediated Diseases, The Second Hospital of Anhui Medical University, Hefei, Anhui, China
- Experimental Teaching Center for Preventive Medicine, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| |
Collapse
|
|
21
|
Motta CS, Torices S, da Rosa BG, Marcos AC, Alvarez-Rosa L, Siqueira M, Moreno-Rodriguez T, Matos ADR, Caetano BC, Martins JSCDC, Gladulich L, Loiola E, Bagshaw ORM, Stuart JA, Siqueira MM, Stipursky J, Toborek M, Adesse D. Human Brain Microvascular Endothelial Cells Exposure to SARS-CoV-2 Leads to Inflammatory Activation through NF-κB Non-Canonical Pathway and Mitochondrial Remodeling. Viruses 2023; 15:745. [PMID: 36992454 PMCID: PMC10056985 DOI: 10.3390/v15030745] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/10/2023] [Accepted: 03/03/2023] [Indexed: 03/15/2023] Open
Abstract
Neurological effects of COVID-19 and long-COVID-19, as well as neuroinvasion by SARS-CoV-2, still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro exposure by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the blood-brain barrier. Despite the low to non-productive viral replication, SARS-CoV-2-exposed cultures displayed increased immunoreactivity for cleaved caspase-3, an indicator of apoptotic cell death, tight junction protein expression, and immunolocalization. Transcriptomic profiling of SARS-CoV-2-challenged cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
Collapse
Affiliation(s)
- Carolline Soares Motta
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Silvia Torices
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Barbara Gomes da Rosa
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Anne Caroline Marcos
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Liandra Alvarez-Rosa
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro 05508-000, Brazil
| | - Michele Siqueira
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro 05508-000, Brazil
| | - Thaidy Moreno-Rodriguez
- Urology Department, University of California San Francisco, San Francisco, CA 94143, USA
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA
| | - Aline da Rocha Matos
- Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Braulia Costa Caetano
- Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Jessica Santa Cruz de Carvalho Martins
- Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Luis Gladulich
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Erick Loiola
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Olivia R. M. Bagshaw
- Faculty of Mathematics & Science, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Jeffrey A. Stuart
- Faculty of Mathematics & Science, Brock University, St. Catharines, ON L2S 3A1, Canada
| | - Marilda M. Siqueira
- Laboratório de Vírus Respiratórios, Exantemáticos, Enterovírus e Emergências Virais (LVRE), Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
| | - Joice Stipursky
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro 05508-000, Brazil
| | - Michal Toborek
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| | - Daniel Adesse
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
| |
Collapse
|
|
22
|
Najafipour R, Mohammadi D, Momeni A, Moghbelinejad S. Effect of B12 and folate deficiency in hypomethylation of Angiotensin I converting enzyme 2 gene and severity of disease among the acute respiratory distress syndrome patients. J Clin Lab Anal 2023; 37:e24846. [PMID: 36877757 PMCID: PMC10098068 DOI: 10.1002/jcla.24846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 12/24/2022] [Accepted: 01/26/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Angiotensin I converting enzyme 2 (ACE-2) is the most important receptor and has important role in the entry of corona virus to the host cells. The present study aimed to investigate the different mechanisms involved in the expression regulation of this gene among the COVID-19 patients. METHODS A total of 140 patients with COVID-19 (n = 70 mild COVID-19, n = 70 ARDS) and 120 controls were recruited. The expression of ACE-2 and miRNAs was evaluated by quantitative real-time PCR (QRT-PCR), and methylation of CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyro-sequencing. Finally, different polymorphisms of the ACE-2 gene were studied by Sanger sequencing. RESULTS Our results showed a significant high expression of the ACE-2 gene in the blood samples of acute respiratory distress syndrome (ARDS) patients (3.8 ± 0.77) in comparison with controls (0.88 ± 0.12; p < 0.03). The methylation rate of the ACE-2 gene in ARDS patients was 14.07 ± 6.1 compared with controls (72.3 ± 5.1; p < 0.0001). Among the four studied miRNAs, only miR200c-3p showed significant downregulation in ARDS patients (0.14 ± 0.1) in comparison with controls (0.32 ± 0.17; p < 0.001). We did not see a substantial difference in the frequency of rs182366225 C>T and rs2097723 T>C polymorphisms between patients and controls (p > 0.05). There was a significant correlation between B12 (R = 0.32, p < 0.001), folate (R = 0.37, p < 0.001) deficiency, and hypo-methylation of the ACE-2 gene. CONCLUSION These results for the first time indicated that among the different mechanisms of ACE-2 expression regulation, its promoter methylation is very crucial and can be affected by factors involved in one-carbon metabolisms such as B9 and B12 vitamins deficiency.
Collapse
Affiliation(s)
- Reza Najafipour
- Genetics Research Center, the University of Social Welfare and Rehabilitation Science, Tehran, Iran
| | - Davood Mohammadi
- Department of Surgery, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | | | - Sahar Moghbelinejad
- Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran
| |
Collapse
|
|
23
|
Behura A, Naik L, Patel S, Das M, Kumar A, Mishra A, Nayak DK, Manna D, Mishra A, Dhiman R. Involvement of epigenetics in affecting host immunity during SARS-CoV-2 infection. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166634. [PMID: 36577469 PMCID: PMC9790847 DOI: 10.1016/j.bbadis.2022.166634] [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: 06/28/2022] [Revised: 10/26/2022] [Accepted: 12/13/2022] [Indexed: 12/27/2022]
Abstract
Coronavirus disease 19 (COVID-19) is caused by a highly contagious RNA virus Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), originated in December 2019 in Wuhan, China. Since then, it has become a global public health concern and leads the disease table with the highest mortality rate, highlighting the necessity for a thorough understanding of its biological properties. The intricate interaction between the virus and the host immune system gives rise to diverse implications of COVID-19. RNA viruses are known to hijack the host epigenetic mechanisms of immune cells to regulate antiviral defence. Epigenetics involves processes that alter gene expression without changing the DNA sequence, leading to heritable phenotypic changes. The epigenetic landscape consists of reversible modifications like chromatin remodelling, DNA/RNA methylation, and histone methylation/acetylation that regulates gene expression. The epigenetic machinery contributes to many aspects of SARS-CoV-2 pathogenesis, like global DNA methylation and receptor angiotensin-converting enzyme 2 (ACE2) methylation determines the viral entry inside the host, viral replication, and infection efficiency. Further, it is also reported to epigenetically regulate the expression of different host cytokines affecting antiviral response. The viral proteins of SARS-CoV-2 interact with various host epigenetic enzymes like histone deacetylases (HDACs) and bromodomain-containing proteins to antagonize cellular signalling. The central role of epigenetic factors in SARS-CoV-2 pathogenesis is now exploited as promising biomarkers and therapeutic targets against COVID-19. This review article highlights the ability of SARS-CoV-2 in regulating the host epigenetic landscape during infection leading to immune evasion. It also discusses the ongoing therapeutic approaches to curtail and control the viral outbreak.
Collapse
Affiliation(s)
- Assirbad Behura
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Lincoln Naik
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Salina Patel
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Mousumi Das
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Ashish Kumar
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Abtar Mishra
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Dev Kiran Nayak
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Debraj Manna
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India
| | - Amit Mishra
- Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342011, India
| | - Rohan Dhiman
- Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India.
| |
Collapse
|
|
24
|
Jiang X, Sparks J, Wallace Z, Deng X, Li H, Lu N, Xie D, Wang Y, Zeng C, Lei G, Wei J, Zhang Y. Risk of COVID-19 among unvaccinated and vaccinated patients with systemic lupus erythematosus: a general population study. RMD Open 2023; 9:e002839. [PMID: 36889799 PMCID: PMC10008206 DOI: 10.1136/rmdopen-2022-002839] [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: 11/04/2022] [Accepted: 02/24/2023] [Indexed: 03/10/2023] Open
Abstract
OBJECTIVE To compare the risk of SARS-CoV-2 infection and its related severe sequelae between patients with systemic lupus erythematosus (SLE) and the general population according to COVID-19 vaccination status. METHODS We performed cohort studies using data from The Health Improvement Network to compare the risks of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population. Individuals aged 18-90 years with no previously documented SARS-CoV-2 infection were included. We estimated the incidence rates and HRs of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population according to COVID-19 vaccination status using exposure score overlap weighted Cox proportional hazards model. RESULTS We identified 3245 patients with SLE and 1 755 034 non-SLE individuals from the unvaccinated cohort. The rates of SARS-CoV-2 infection, COVID-19 hospitalisation, COVID-19 death and combined severe outcomes per 1000 person-months were 10.95, 3.21, 1.16 and 3.86 among patients with SLE, and 8.50, 1.77, 0.53 and 2.18 among general population, respectively. The corresponding adjusted HRs were 1.28 (95% CI: 1.03 to 1.59), 1.82 (95% CI: 1.21 to 2.74), 2.16 (95% CI: 1.00 to 4.79) and 1.78 (95% CI: 1.21 to 2.61). However, no statistically significant differences were observed between vaccinated patients with SLE and vaccinated general population over 9 months of follow-up. CONCLUSION While unvaccinated patients with SLE were at higher risk of SARS-CoV-2 infection and its severe sequelae than the general population, no such difference was observed among vaccinated population. The findings indicate that COVID-19 vaccination provides an adequate protection to most patients with SLE from COVID-19 breakthrough infection and its severe sequelae.
Collapse
Affiliation(s)
- Xiaofeng Jiang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Jeffrey Sparks
- Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Zachary Wallace
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Xinjia Deng
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Hui Li
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Na Lu
- Arthritis Research Canada, Richmond, British Columbia, Canada
| | - Dongxing Xie
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Yilun Wang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
| | - Chao Zeng
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Guanghua Lei
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jie Wei
- Health Management Center, Xiangya Hospital, Central South University, Changsha, China
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
| | - Yuqing Zhang
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- The Mongan Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
25
|
Huang HC, Wang SH, Fang GC, Chou WC, Liao CC, Sun CP, Jan JT, Ma HH, Ko HY, Ko YA, Chiang MT, Liang JJ, Kuo CT, Lee TA, Morales-Scheihing D, Shen CY, Chen SY, McCullough LD, Cui L, Wernig G, Tao MH, Lin YL, Chang YM, Wang SP, Lai YJ, Li CW. Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion. J Med Virol 2023; 95:e28478. [PMID: 36609964 PMCID: PMC10107526 DOI: 10.1002/jmv.28478] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 12/15/2022] [Accepted: 01/03/2023] [Indexed: 01/08/2023]
Abstract
Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.
Collapse
Affiliation(s)
- Hsiang-Chi Huang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Shih-Han Wang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Guo-Chen Fang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Wen-Cheng Chou
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Chun-Che Liao
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Cheng-Pu Sun
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Jia-Tsrong Jan
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hsiu-Hua Ma
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hui-Ying Ko
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Yi-An Ko
- Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan
| | - Ming-Tsai Chiang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Jian-Jong Liang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Chun-Tse Kuo
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Te-An Lee
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Diego Morales-Scheihing
- Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Chen-Yang Shen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Shih-Yu Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Louise D McCullough
- Department of Neurology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Lu Cui
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California, USA
| | - Gerlinde Wernig
- Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.,Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California, USA
| | - Mi-Hua Tao
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.,Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan
| | - Yi-Ling Lin
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.,Biomedical Translational Research Center, Academia Sinica, Taipei, Taiwan
| | - Yao-Ming Chang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Shu-Ping Wang
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| | - Yun-Ju Lai
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.,Solomont School of Nursing, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Chia-Wei Li
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
| |
Collapse
|
|
26
|
Hamidi Z, Jabraeili-Siahroud S, Taati-Alamdari Y, Aghbash PS, Shamekh A, Baghi HB. A comprehensive review of COVID-19 symptoms and treatments in the setting of autoimmune diseases. Virol J 2023; 20:1. [PMID: 36611166 PMCID: PMC9824943 DOI: 10.1186/s12985-023-01967-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 01/04/2023] [Indexed: 01/09/2023] Open
Abstract
After the first reporting of the index case of Severe Acute Respiratory Syndrome (SARS)-CoV-2-associated disease at the end of December 2019, the virus spread quickly throughout the world, prompting the WHO on 11 March 2020 to declare the disease a global pandemic. The coronavirus disease 2019 (COVID-19) pandemic, raises concerns for all people, mainly for susceptible population. People with pre-existing diseases, especially individuals with autoimmune disorders, are more at the risk of SARS-CoV-2 infection because of compromised immune system due to frequent use of immunosuppressive drugs and steroids. Patients with autoimmune diseases and their physicians have concerns about these patients' healthcare, since they are at a higher risk for COVID-19 infection, may show severe complications of COVID-19, and may experience probable flares of their pre-existing disease. Even though there have been several studies discussing the relation between COVID-19 and various types of autoimmune diseases, it cannot be ascertained that all patients with autoimmune diseases experience more severe complications of COVID-19 and have more hospitalization or mortality rate. The situation depends on each patient's condition, such as the type and the severity of the underlying autoimmune disease and the kind of treatment they receive. In the present review, we have discussed the effects of COVID-19 pandemic on patients with different autoimmune diseases and their relative concerns about their treatments. As a result, we have reviewed further considerations that should be taken into account for these patients during the pandemic or when they are infected with COVID-19.
Collapse
Affiliation(s)
- Zahra Hamidi
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shaghaiegh Jabraeili-Siahroud
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yalda Taati-Alamdari
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Shiri Aghbash
- grid.412888.f0000 0001 2174 8913Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Shamekh
- grid.412888.f0000 0001 2174 8913Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran ,grid.412888.f0000 0001 2174 8913Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5165665931, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. .,Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5165665931, Tabriz, Iran.
| |
Collapse
|
|
27
|
Hamidi Z, Jabraeili-Siahroud S, Taati-Alamdari Y, Aghbash PS, Shamekh A, Baghi HB. A comprehensive review of COVID-19 symptoms and treatments in the setting of autoimmune diseases. Virol J 2023. [PMID: 36611166 DOI: 10.1186/s12985-023-01967-7/tables/1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2023] Open
Abstract
After the first reporting of the index case of Severe Acute Respiratory Syndrome (SARS)-CoV-2-associated disease at the end of December 2019, the virus spread quickly throughout the world, prompting the WHO on 11 March 2020 to declare the disease a global pandemic. The coronavirus disease 2019 (COVID-19) pandemic, raises concerns for all people, mainly for susceptible population. People with pre-existing diseases, especially individuals with autoimmune disorders, are more at the risk of SARS-CoV-2 infection because of compromised immune system due to frequent use of immunosuppressive drugs and steroids. Patients with autoimmune diseases and their physicians have concerns about these patients' healthcare, since they are at a higher risk for COVID-19 infection, may show severe complications of COVID-19, and may experience probable flares of their pre-existing disease. Even though there have been several studies discussing the relation between COVID-19 and various types of autoimmune diseases, it cannot be ascertained that all patients with autoimmune diseases experience more severe complications of COVID-19 and have more hospitalization or mortality rate. The situation depends on each patient's condition, such as the type and the severity of the underlying autoimmune disease and the kind of treatment they receive. In the present review, we have discussed the effects of COVID-19 pandemic on patients with different autoimmune diseases and their relative concerns about their treatments. As a result, we have reviewed further considerations that should be taken into account for these patients during the pandemic or when they are infected with COVID-19.
Collapse
Affiliation(s)
- Zahra Hamidi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shaghaiegh Jabraeili-Siahroud
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Yalda Taati-Alamdari
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Shamekh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5165665931, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P.O. Box 5165665931, Tabriz, Iran.
| |
Collapse
|
|
28
|
Sen R, Sarkar S, Chlamydas S, Garbati M, Barnes C. Epigenetic features, methods, and implementations associated with COVID-19. OMICS APPROACHES AND TECHNOLOGIES IN COVID-19 2023:161-175. [DOI: 10.1016/b978-0-323-91794-0.00008-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
29
|
Papagerakis S, Said R, Ketabat F, Mahmood R, Pundir M, Lobanova L, Guenther G, Pannone G, Lavender K, McAlpin BR, Moreau A, Chen X, Papagerakis P. When the clock ticks wrong with COVID-19. Clin Transl Med 2022; 12:e949. [PMID: 36394205 PMCID: PMC9670202 DOI: 10.1002/ctm2.949] [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: 03/11/2022] [Revised: 06/06/2022] [Accepted: 06/11/2022] [Indexed: 11/18/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID-19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes. The circadian clock is a critical regulatory mechanism orchestrating major physiological and pathological processes. It is generally accepted that more than half of the cell-specific genes in any given organ are under circadian control. Although it is known that a specific role of the circadian clock is to coordinate the immune system's steady-state function and response to infectious threats, the links between the circadian clock and SARS-CoV-2 infection are only now emerging. How inter-individual variability of the circadian profile and its dysregulation may play a role in the differences noted in the COVID-19-related disease presentations, and outcome remains largely underinvestigated. This review summarizes the current evidence on the potential links between circadian clock dysregulation and SARS-CoV-2 infection susceptibility, disease presentation and progression, and clinical outcomes. Further research in this area may contribute towards novel circadian-centred prognostic, diagnostic and therapeutic approaches for COVID-19 in the era of precision health.
Collapse
Affiliation(s)
- Silvana Papagerakis
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Biochemistry, Microbiology and Immunology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Otolaryngology – Head and Neck Surgery, Medical SchoolThe University of MichiganAnn ArborMichiganUSA
| | - Raed Said
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Anatomy, Physiology and Pharmacology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Farinaz Ketabat
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Razi Mahmood
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Surgery, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Meenakshi Pundir
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Liubov Lobanova
- Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Greg Guenther
- Laboratory of Oral, Head and Neck Cancer – Personalized Diagnostics and Therapeutics, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Giuseppe Pannone
- Anatomic Pathology Unit, Department of Clinic and Experimental MedicineUniversity of FoggiaFoggiaItaly
| | - Kerry Lavender
- Department of Biochemistry, Microbiology and Immunology, College of MedicineUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Blake R. McAlpin
- Laboratories of Neuroimmunology, Department of Symptom Research, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Alain Moreau
- Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal DiseasesCentre Hospitalier Universitaire (CHU) Sainte‐Justine Research CenterMontrealQuebecCanada,Department of Stomatology, Faculty of Dentistry and Department of Biochemistry and Molecular Medicine, Faculty of MedicineUniversité de MontréalMontrealQuebecCanada
| | - Xiongbiao Chen
- Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Department of Mechanical Engineering, School of EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| | - Petros Papagerakis
- Division of Biomedical EngineeringUniversity of SaskatchewanSaskatoonSaskatchewanCanada,Laboratory of Precision Oral Health and Chronobiology, College of DentistryUniversity of SaskatchewanSaskatoonSaskatchewanCanada
| |
Collapse
|
|
30
|
Zhu X, Trimarco JD, Williams CA, Barrera A, Reddy TE, Heaton NS. ZBTB7A promotes virus-host homeostasis during human coronavirus 229E infection. Cell Rep 2022; 41:111540. [PMID: 36243002 PMCID: PMC9533670 DOI: 10.1016/j.celrep.2022.111540] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/24/2022] [Accepted: 09/29/2022] [Indexed: 11/22/2022] Open
Abstract
The cellular fate after infection with human coronaviruses (HCoVs) is typically death. Previous data suggest, however, that the transcriptional state of an individual cell may sometimes allow additional outcomes of infection. Here, to probe the range of interactions a permissive cell type can have with a HCoV, we perform a CRISPR activation screen with HCoV-229E. The screen identified the transcription factor ZBTB7A, which strongly promotes cell survival after infection. Rather than suppressing viral infection, ZBTB7A upregulation allows the virus to induce a persistent infection and homeostatic state with the cell. We also find that control of oxidative stress is a primary driver of cellular survival during HCoV-229E infection. These data illustrate that, in addition to the nature of the infecting virus and the type of cell that it encounters, the cellular gene expression profile prior to infection can affect the eventual fate.
Collapse
Affiliation(s)
- Xinyu Zhu
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA
| | - Joseph D. Trimarco
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA
| | - Courtney A. Williams
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA,Center for Genomic and Computational Biology, Duke University, Durham, NC, USA,Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA
| | - Alejandro Barrera
- Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA,Center for Genomic and Computational Biology, Duke University, Durham, NC, USA,Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA
| | - Timothy E. Reddy
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA,Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA,Center for Genomic and Computational Biology, Duke University, Durham, NC, USA,Center for Advanced Genomic Technologies, Duke University, Durham, NC, USA,Department of Biomedical Engineering, Duke University, Durham, NC, USA
| | - Nicholas S. Heaton
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA,Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA,Corresponding author
| |
Collapse
|
|
31
|
Foolchand A, Mazaleni S, Ghazi T, Chuturgoon AA. A Review: Highlighting the Links between Epigenetics, COVID-19 Infection, and Vitamin D. Int J Mol Sci 2022; 23:12292. [PMID: 36293144 PMCID: PMC9603374 DOI: 10.3390/ijms232012292] [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: 09/12/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
The highly transmittable and infectious COVID-19 remains a major threat worldwide, with the elderly and comorbid individuals being the most vulnerable. While vaccines are currently available, therapeutic drugs will help ease the viral outbreak and prevent serious health outcomes. Epigenetic modifications regulate gene expression through changes in chromatin structure and have been linked to viral pathophysiology. Since epigenetic modifications contribute to the life cycle of the virus and host immune responses to infection, epigenetic drugs are promising treatment targets to ameliorate COVID-19. Deficiency of the multifunctional secosteroid hormone vitamin D is a global health threat. Vitamin D and its receptor function to regulate genes involved in immunity, apoptosis, proliferation, differentiation, and inflammation. Amassed evidence also indicates the biological relations of vitamin D with reduced disease risk, while its receptor can be modulated by epigenetic mechanisms. The immunomodulatory effects of vitamin D suggest a role for vitamin D as a COVID-19 therapeutic agent. Therefore, this review highlights the epigenetic effects on COVID-19 and vitamin D while also proposing a role for vitamin D in COVID-19 infections.
Collapse
Affiliation(s)
| | | | - Terisha Ghazi
- Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Howard College Campus, Durban 4041, South Africa
| | - Anil A. Chuturgoon
- Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Howard College Campus, Durban 4041, South Africa
| |
Collapse
|
|
32
|
Najafipour R, Mohammadi D, Momeni M, Moghbelinejad S. ACE-2 Expression and Methylation Pattern in Bronchoalveolar Lavage Fluid and Bloods of Iranian ARDS Covid-19 Patients. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2022; 11:55-63. [PMID: 36397811 PMCID: PMC9653551 DOI: 10.22088/ijmcm.bums.11.1.55] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/17/2022] [Accepted: 08/22/2022] [Indexed: 06/16/2023]
Abstract
The aim of the present study was to investigate the expression and methylation pattern of the angiotensin I converting enzyme 2 (ACE-2) in acute respiratory distress syndrome (ARDS) covid-9 patients. A total of 25 patients with covid-19 ARDS and 20 controls were recruited. Expression of the ACE-2 gene was evaluated by quantitative real time PCR, and methylation of CpG dinucleotides, in the ACE-2 promoter, was quantified using bisulfite pyro-sequencing. Our results showed high expression of the ACE-2 gene in the blood samples of ADRS patients (1.93± 0.67) in comparison to controls (0.62±0.35) (P = 0.03). Correspondingly, in ARDS bronchoalveolar lavage fluid (BALF) samples, there was a high expression of this gene (1.8±0.78) in comparison to controls (0.58±0.2) (p <0.05). Moreover, the methylation rate of the ACE-2 gene in blood samples of ARDS patients was 64.07 ±6.1 in comparison to controls (80.3 ±7.3) (p<0.0001). In BALF samples, there was this pattern too (55.07 ±3.1 vs. 72.35±5.1) (p<0.0001). Finally, a significant correlation was found between expression and methylation in BALF (R= -0.54, P= 0.002) and blood (R= -0.321, P= 0.013) samples. These results indicated that aberrant methylation of the ACE-2 promoter might be associated with high expression of this gene and the occurrence of ARDS in covid-19 patients.
Collapse
Affiliation(s)
- Reza Najafipour
- Genetics Research Center, the University of Social Welfare and Rehabilitation Science, Tehran, Iran.
| | - Davood Mohammadi
- Department of Surgery, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
| | | | - Sahar Moghbelinejad
- Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Centre, Qazvin University of Medical Sciences, Qazvin, Iran.
| |
Collapse
|
|
33
|
Delshad M, Sanaei MJ, Pourbagheri-Sigaroodi A, Bashash D. Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination. Int Immunopharmacol 2022; 111:109128. [PMID: 35963158 PMCID: PMC9359488 DOI: 10.1016/j.intimp.2022.109128] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 07/15/2022] [Accepted: 08/03/2022] [Indexed: 12/14/2022]
Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the outbreak of coronavirus disease 2019 (COVID-19), has shown a vast range of clinical manifestations from asymptomatic to life-threatening symptoms. To figure out the cause of this heterogeneity, studies demonstrated the trace of genetic diversities whether in the hosts or the virus itself. With this regard, this review provides a comprehensive overview of how host genetic such as those related to the entry of the virus, the immune-related genes, gender-related genes, disease-related genes, and also host epigenetic could influence the severity of COVID-19. Besides, the mutations in the genome of SARS-CoV-2 __leading to emerging of new variants__ per se affect the affinity of the virus to the host cells and enhance the immune escape capacity. The current review discusses these variants and also the latest data about vaccination effectiveness facing the most important variants.
Collapse
Affiliation(s)
- Mahda Delshad
- Department of Laboratory Sciences, School of Allied Medical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohammad-Javad Sanaei
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atieh Pourbagheri-Sigaroodi
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Bashash
- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
34
|
Hejazian SS, Hejazian SM, Farnood F, Abedi Azar S. Dysregulation of immunity in COVID-19 and SLE. Inflammopharmacology 2022; 30:1517-1531. [PMID: 36028612 PMCID: PMC9417079 DOI: 10.1007/s10787-022-01047-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 07/30/2022] [Indexed: 12/15/2022]
Abstract
The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19.
Collapse
Affiliation(s)
- Seyyed Sina Hejazian
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Farahnoosh Farnood
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sima Abedi Azar
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
35
|
Bhat S, Rishi P, Chadha VD. Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches. Virus Res 2022; 318:198853. [PMID: 35777502 PMCID: PMC9236910 DOI: 10.1016/j.virusres.2022.198853] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 06/14/2022] [Accepted: 06/26/2022] [Indexed: 11/29/2022]
Abstract
COVID-19 pandemic caused by the Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) has inflicted a global health challenge. Although the overwhelming escalation of mortality seen during the initial phase of the pandemic has reduced, emerging variants of SARS-CoV-2 continue to impact communities worldwide. Several studies have highlighted the association of gene specific epigenetic modifications in host cells with the pathogenesis and severity of the disease. Therefore, alongside the investigations into the virology and pathogenesis of SARS-CoV-2 infection, understanding the epigenetic mechanisms related to the disease is crucial for the rational design of effective targeted therapies. Here, we discuss the interaction of SARS-CoV-2 with the various epigenetic regulators and their subsequent contribution to the risk of disease severity and dysfunctional immune responses. Finally, we also highlight the use of epigenetically targeted drugs for the potential therapeutic interventions capable of eliminating viral infection and/or build effective immunity against it.
Collapse
Affiliation(s)
- Swati Bhat
- Center for Nuclear Medicine (U.I.E.A.S.T), South Campus, Panjab University, Sector 25, Chandigarh 160014, India.
| | - Praveen Rishi
- Department of Microbiology, South Campus, Panjab University, Sector 25, Chandigarh 160014, India.
| | - Vijayta D Chadha
- Center for Nuclear Medicine (U.I.E.A.S.T), South Campus, Panjab University, Sector 25, Chandigarh 160014, India.
| |
Collapse
|
|
36
|
Patra SK, Szyf M. Epigenetic perspectives of COVID-19: Virus infection to disease progression and therapeutic control. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166527. [PMID: 36002132 PMCID: PMC9393109 DOI: 10.1016/j.bbadis.2022.166527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/05/2022] [Accepted: 08/18/2022] [Indexed: 11/20/2022]
Abstract
COVID-19 has caused numerous deaths as well as imposed social isolation and upheaval world-wide. Although, the genome and the composition of the virus, the entry process and replication mechanisms are well investigated from by several laboratories across the world, there are many unknown remaining questions. For example, what are the functions of membrane lipids during entry, packaging and exit of virus particles? Also, the metabolic aspects of the infected tissue cells are poorly understood. In the course of virus replication and formation of virus particles within the host cell, the enhanced metabolic activities of the host is directly proportional to viral loads. The epigenetic landscape of the host cells is also altered, particularly the expression/repression of genes associated with cellular metabolism as well as cellular processes that are antagonistic to the virus. Metabolic pathways are enzyme driven processes and the expression profile and mechanism of regulations of the respective genes encoding those enzymes during the course of pathogen invasion might be highly informative on the course of the disease. Recently, the metabolic profile of the patients' sera have been analysed from few patients. In view of this, and to gain further insights into the roles that epigenetic mechanisms might play in this scenario in regulation of metabolic pathways during the progression of COVID-19 are discussed and summarised in this contribution for ensuring best therapy.
Collapse
Affiliation(s)
- Samir Kumar Patra
- Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India.
| | - Moshe Szyf
- Department of Pharmacology & Therapeutics, McIntyre Medical Sciences Building, McGill University, Montreal, QC H3G 1Y6, Canada
| |
Collapse
|
|
37
|
Humoral and cellular response in convalescent COVID-19 lupus patients. Sci Rep 2022; 12:13787. [PMID: 35962159 PMCID: PMC9374301 DOI: 10.1038/s41598-022-17334-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 07/25/2022] [Indexed: 01/08/2023] Open
Abstract
In SLE, underlying immune dysregulation and immunosuppression may increase the susceptibility to COVID-19 and impair the humoral and adaptive response. We aimed to characterize COVID-19 infection, identifying susceptibility and severity risk factors, assessing the presence of SARS-CoV-2 IgG antibodies and analyzing the cellular response. We established a prospective cohort of lupus patients to estimate the COVID-19 incidence compared to the reference general population. Data were collected via telephone interviews and medical record review. SARS-CoV-2 IgG antibodies were measured cross-sectionally as part of routine surveillance. Longitudinal changes in antibody titers and immunological profile from convalescent COVID-19 patients were evaluated at 6, 12 and 24 week after symptom onset. From immunological studies, PBMCs from convalescent patients were extracted and analyzed by flow cytometry and gene expression analysis. We included 725 patients, identifying 29 with PCR-confirmed COVID-19 infection and 16 with COVID-19-like symptoms without PCR-testing. Of the 29 confirmed cases, 7 had severe disease, 8 required hospital admission (27.6%), 4 intensive care, and 1 died. COVID-19 accumulated incidence was higher in lupus patients. Health care workers and anti-SSA/Ro52 antibody positivity were risk factors for COVID-19 susceptibility, and hypocomplementemia for severity. SARS-CoV-2 IgG antibodies were detected in 8.33% of patients. Three fourths of confirmed COVID-19 cases developed antibodies. High prednisone doses were associated with lack of antibody response. Antibody titers declined over time (39%). Convalescent patients at week 12 after symptom onset displayed a CD8+T cell reduction and predominant Th17 with a mild Th2 response, more pronounced in severe COVID-19 disease. Longitudinal immune response analysis showed a progressive sustained increase in CD8+ T and B memory cells with a decrease of Th17 signaling. Lupus patients are at higher risk of COVID-19 infection and new susceptibility and severity risk factors were identified. Lupus patients were able to mount humoral and cellular responses despite immunosuppressive therapy.
Collapse
|
|
38
|
Zelop CM, Bonney EA. COVID-19 in pregnancy: possible mechanisms not to be discounted. J Matern Fetal Neonatal Med 2022; 35:3016-3019. [PMID: 32811230 PMCID: PMC10430893 DOI: 10.1080/14767058.2020.1807508] [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: 07/03/2020] [Revised: 07/27/2020] [Accepted: 08/05/2020] [Indexed: 10/23/2022]
Abstract
SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus-receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy.
Collapse
Affiliation(s)
- Carolyn M Zelop
- The Valley Hospital, Ridgewood, Paramus, NJ, USA
- New York University New York, NY, USA
| | - Elizabeth A Bonney
- Division of Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont Larner College of Medicine, Burlington, VT, USA
| |
Collapse
|
|
39
|
Ahmad S, Manzoor S, Siddiqui S, Mariappan N, Zafar I, Ahmad A, Ahmad A. Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19. Semin Cancer Biol 2022; 83:384-398. [PMID: 33484868 PMCID: PMC8046427 DOI: 10.1016/j.semcancer.2021.01.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/08/2020] [Accepted: 01/07/2021] [Indexed: 12/11/2022]
Abstract
Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.
Collapse
Affiliation(s)
- Shama Ahmad
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Shajer Manzoor
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Simmone Siddiqui
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Nithya Mariappan
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Iram Zafar
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Aamir Ahmad
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Aftab Ahmad
- Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
| |
Collapse
|
|
40
|
Al-Beltagi M, Saeed NK, Bediwy AS. COVID-19 disease and autoimmune disorders: A mutual pathway. World J Methodol 2022; 12:200-223. [PMID: 36159097 PMCID: PMC9350728 DOI: 10.5662/wjm.v12.i4.200] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 06/17/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a real challenge for humanity with high morbidity and mortality. Despite being primarily a respiratory illness, COVID-19 can affect nearly every human body tissue, causing many diseases. After viral infection, the immune system can recognize the viral antigens presented by the immune cells. This immune response is usually controlled and terminated once the infection is aborted. Nevertheless, in some patients, the immune reaction becomes out of control with the development of autoimmune diseases. Several human tissue antigens showed a strong response with antibodies directed against many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins, such as SARS-CoV-2 S, N, and autoimmune target proteins. The immunogenic effects of SARS-CoV-2 are due to the sizeable viral RNA molecules with interrupted transcription increasing the pool of epitopes with increased chances of molecular mimicry and interaction with the host immune system, the overlap between some viral and human peptides, the viral induced-tissue damage, and the robust and complex binding between sACE-2 and SARS-CoV-2 S protein. Consequently, COVID-19 and its vaccine may trigger the development of many autoimmune diseases in a predisposed patient. This review discusses the mutual relation between COVID-19 and autoimmune diseases, their interactive effects on each other, the role of the COVID-19 vaccine in triggering autoimmune diseases, the factors affecting the severity of COVID-19 in patients suffering from autoimmune diseases, and the different ways to minimize the risk of COVID-19 in patients with autoimmune diseases.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al-Habib Medical Group, Manama 26671, Manama, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Manama, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Algharbia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al-Habib Medical Group, Manama 26671, Manama, Bahrain
| |
Collapse
|
|
41
|
Alexescu TG, Nechita MS, Maierean AD, Vulturar DM, Handru MI, Leucuța DC, Orășan OH, Negrean V, Ciumarnean L, Todea DA. Change in Neuroticism and Extraversion among Pre-University Education Employees during the COVID-19 Pandemic. Medicina (B Aires) 2022; 58:medicina58070895. [PMID: 35888616 PMCID: PMC9324659 DOI: 10.3390/medicina58070895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 11/16/2022] Open
Abstract
Background and objectives: Since the first reports of SARS-CoV-2 infection cases in China, the virus has rapidly spread to many countries, including Romania. In Romania, schools were closed in March 2020 to prevent the virus from spreading; since then, they have been sporadically opened, but only for a short time. Teachers had to adopt online education methods, experiencing real difficulties in their attempts to maintain high-quality teaching, as a result of social distancing from students and colleagues. The current study aimed to evaluate the burden on the neuroticism states of employees in the pre-university education system during the COVID-19 pandemic. Materials and Methods: A prospective study was conducted, in which personality trait data from 138 employees were collected via a questionnaire (EPI, Eysenck Personality Inventory), which measured extraversion–introversion and neuroticism scores before and during the COVID-19 pandemic. Initially, 150 subjects were invited to participate in the study, although 12 of them refused to participate. Based on the questionnaire not being fully filled in a further three subjects were excluded from the study, leaving a total of 135, of which 115 were woman and 20 were men. Results: The results demonstrate that the subjects included in the study expressed higher neuroticism during the COVID-19 pandemic than in the pre-pandemic period. This change could promote more stress and depression symptoms. Subjects with high school education had significantly lower neuroticism scores over time than those with university education (p = 0.006). Furthermore, we found extraversion scores to be statistically significant in our population (p = 0.022). Conclusion: The gender and living environment of the teachers were not significantly associated with the reduction in the extraversion score, but were more frequently found among older persons and in subjects without higher education. Subjects of Hungarian ethnicity had lower extraversion scores than those of Romanian ethnicity.
Collapse
Affiliation(s)
- Teodora-Gabriela Alexescu
- 5th Departament Internal Medicine, 4th Medical Clinic, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (T.-G.A.); (O.H.O.); (V.N.); (L.C.)
| | | | - Anca-Diana Maierean
- Department of Pneumology, University of Medicine and Pharmacy, 400332 Cluj-Napoca, Romania; (A.-D.M.); (D.A.T.)
| | - Damiana-Maria Vulturar
- Department of Pneumology, University of Medicine and Pharmacy, 400332 Cluj-Napoca, Romania; (A.-D.M.); (D.A.T.)
- Correspondence:
| | | | - Daniel-Corneliu Leucuța
- Department of Informatics and Biostatistics, University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Olga Hilda Orășan
- 5th Departament Internal Medicine, 4th Medical Clinic, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (T.-G.A.); (O.H.O.); (V.N.); (L.C.)
| | - Vasile Negrean
- 5th Departament Internal Medicine, 4th Medical Clinic, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (T.-G.A.); (O.H.O.); (V.N.); (L.C.)
| | - Lorena Ciumarnean
- 5th Departament Internal Medicine, 4th Medical Clinic, University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (T.-G.A.); (O.H.O.); (V.N.); (L.C.)
| | - Doina Adina Todea
- Department of Pneumology, University of Medicine and Pharmacy, 400332 Cluj-Napoca, Romania; (A.-D.M.); (D.A.T.)
| |
Collapse
|
|
42
|
Abstract
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a global pandemic impacting 254 million people in 190 countries. Comorbidities, particularly cardiovascular disease, diabetes, and hypertension, increase the risk of infection and poor outcomes. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme-2 receptor, generating inflammation and cytokine storm, often resulting in multiorgan failure. The mechanisms and effects of COVID-19 on patients with high-risk diabetes are not yet completely understood. In this review, we discuss the variety of coronaviruses, structure of SARS-CoV-2, mutations in SARS-CoV-2 spike proteins, receptors associated with viral host entry, and disease progression. Furthermore, we focus on possible mechanisms of SARS-CoV-2 in diabetes, leading to inflammation and heart failure. Finally, we discuss existing therapeutic approaches, unanswered questions, and future directions.
Collapse
Affiliation(s)
- Chandrakala Aluganti Narasimhulu
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States
| | - Dinender K Singla
- Division of Metabolic and Cardiovascular Sciences, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States
| |
Collapse
|
|
43
|
Chlamydas S, Markouli M, Strepkos D, Piperi C. Epigenetic mechanisms regulate sex-specific bias in disease manifestations. J Mol Med (Berl) 2022; 100:1111-1123. [PMID: 35764820 PMCID: PMC9244100 DOI: 10.1007/s00109-022-02227-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 06/02/2022] [Accepted: 06/20/2022] [Indexed: 12/15/2022]
Abstract
Abstract Sex presents a vital determinant of a person’s physiology, anatomy, and development. Recent clinical studies indicate that sex is also involved in the differential manifestation of various diseases, affecting both clinical outcome as well as response to therapy. Genetic and epigenetic changes are implicated in sex bias and regulate disease onset, including the inactivation of the X chromosome as well as sex chromosome aneuploidy. The differential expression of X-linked genes, along with the presence of sex-specific hormones, exhibits a significant impact on immune system function. Several studies have revealed differences between the two sexes in response to infections, including respiratory diseases and COVID-19 infection, autoimmune disorders, liver fibrosis, neuropsychiatric diseases, and cancer susceptibility, which can be explained by sex-biased immune responses. In the present review, we explore the input of genetic and epigenetic interplay in the sex bias underlying disease manifestation and discuss their effects along with sex hormones on disease development and progression, aiming to reveal potential new therapeutic targets. Key messages
Sex is involved in the differential manifestation of various diseases. Epigenetic modifications influence X-linked gene expression, affecting immune response to infections, including COVID-19. Epigenetic mechanisms are responsible for the sex bias observed in several respiratory and autoimmune disorders, liver fibrosis, neuropsychiatric diseases, and cancer.
Collapse
Affiliation(s)
- Sarantis Chlamydas
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street Bldg 16, 11527, Athens, Greece.,Olink Proteomics, Uppsala, Sweden
| | - Mariam Markouli
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street Bldg 16, 11527, Athens, Greece
| | - Dimitrios Strepkos
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street Bldg 16, 11527, Athens, Greece
| | - Christina Piperi
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 M. Asias Street Bldg 16, 11527, Athens, Greece.
| |
Collapse
|
|
44
|
Torices S, Motta CS, da Rosa BG, Marcos AC, Alvarez-Rosa L, Siqueira M, Moreno-Rodriguez T, Matos A, Caetano B, Martins J, Gladulich L, Loiola E, Bagshaw ORM, Stuart JA, Siqueira MM, Stipursky J, Toborek M, Adesse D. SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022:2022.06.16.496324. [PMID: 35734080 PMCID: PMC9216721 DOI: 10.1101/2022.06.16.496324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2023]
Abstract
Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non-productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
Collapse
Affiliation(s)
- Silvia Torices
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Carolline Soares Motta
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Barbara Gomes da Rosa
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Anne Caroline Marcos
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Liandra Alvarez-Rosa
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro, Brazil
| | - Michele Siqueira
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro, Brazil
| | - Thaidy Moreno-Rodriguez
- Urology Department, University of California San Francisco, San Francisco, CA, USA
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA
| | - Aline Matos
- Laboratório de Virus Respiratórios e Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Braulia Caetano
- Laboratório de Virus Respiratórios e Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Jessica Martins
- Laboratório de Virus Respiratórios e Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Luis Gladulich
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Erick Loiola
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Olivia RM Bagshaw
- Faculty of Mathematics & Science, Brock University, St. Catharines, Ontario, Canada
| | - Jeffrey A. Stuart
- Faculty of Mathematics & Science, Brock University, St. Catharines, Ontario, Canada
| | - Marilda M. Siqueira
- Laboratório de Virus Respiratórios e Sarampo, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| | - Joice Stipursky
- Laboratório Compartilhado, Instituto de Ciências Biomédicas, UFRJ, Rio de Janeiro, Brazil
| | - Michal Toborek
- Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Daniel Adesse
- Laboratório de Biologia Estrutural, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil
| |
Collapse
|
|
45
|
Torices S, Motta C, da Rosa B, Marcos A, Alvarez-Rosa L, Siqueira M, Moreno-Rodriguez T, Matos A, Caetano B, Martins J, Gladulich L, Loiola E, Bagshaw O, Stuart J, Siqueira M, Stipursky J, Toborek M, Adesse D. SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling. RESEARCH SQUARE 2022:rs.3.rs-1762855. [PMID: 35734086 PMCID: PMC9216729 DOI: 10.21203/rs.3.rs-1762855/v1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose several questions and are of both clinical and scientific relevance. We described the cellular and molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain Barrier. Despite the low to non- productive viral replication, SARS-CoV-2-infected cultures displayed increased apoptotic cell death and tight junction protein expression and immunolocalization. Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability in COVID-19.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | - Aline Matos
- Laboratório de Vírus Respiratório e do Sarampo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Du G, Xu X, Wang J, Wang X, Ding Y, Li F, Sun Y, Tao H, Luo Y, Li H, Bo X, Chen H. The accessible promoter-mediated supplementary effect of host factors provides new insight into the tropism of SARS-CoV-2. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 28:249-258. [PMID: 35313658 PMCID: PMC8925281 DOI: 10.1016/j.omtn.2022.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 03/12/2022] [Indexed: 01/08/2023]
Abstract
In the past year, the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the worldwide coronavirus disease 2019 (COVID-19) pandemic. Yet our understanding of the SARS-CoV-2 tropism mechanism is still insufficient. In this study, we examined the chromatin accessibility at the promoters of host factor genes (ACE2, TMPRSS2, NRP1, BSG, CTSL, and FURIN) in 14 tissue types, 23 tumor types, and 189 cell lines. We showed that the promoters of ACE2 and TMPRSS2 were accessible in a tissue- and cell-specific pattern, which is accordant with previous clinical research on SARS-CoV-2 tropism. We were able to further verify that type I interferon (IFN) could induce angiotensin-converting enzyme 2 (ACE2) expression in Caco-2 cells by enhancing the binding of HNF1A, the transcription factor of ACE2, to ACE2 promoter without changing chromatin accessibility. We then performed transcription factor (TF)-gene interactions network and pathway analyses and discovered that the TFs regulating host factor genes are enriched in pathways associated with viral infection. Finally, we established a novel model that suggests that open chromatin at the promoter mediates the host factors' supplementary effect and ensures SARS-CoV-2 entry. Our work uncovers the relationship between epigenetic regulation and SARS-CoV-2 tropism and provides clues for further investigation of COVID-19 pathogenesis.
Collapse
Affiliation(s)
- Guifang Du
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
- Hepato-pancreato-biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing 102218, China
| | - Xiang Xu
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Junting Wang
- The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
| | - Xuejun Wang
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Yang Ding
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Fei Li
- Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China
| | - Yu Sun
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Huan Tao
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Yawen Luo
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Hao Li
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Xiaochen Bo
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| | - Hebing Chen
- Institute of Health Service and Transfusion Medicine, Beijing 100850, China
| |
Collapse
|
|
47
|
Halawa S, Pullamsetti SS, Bangham CRM, Stenmark KR, Dorfmüller P, Frid MG, Butrous G, Morrell NW, de Jesus Perez VA, Stuart DI, O'Gallagher K, Shah AM, Aguib Y, Yacoub MH. Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective. Nat Rev Cardiol 2022; 19:314-331. [PMID: 34873286 PMCID: PMC8647069 DOI: 10.1038/s41569-021-00640-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2021] [Indexed: 12/13/2022]
Abstract
The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic.
Collapse
Affiliation(s)
| | - Soni S Pullamsetti
- Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
- Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig University, Giessen, Germany
- Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany
| | - Charles R M Bangham
- Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK
| | - Kurt R Stenmark
- Divisions of Paediatric Critical Care Medicine and Cardiovascular Pulmonary Research, University of Colorado Denver, Denver, CO, USA
| | - Peter Dorfmüller
- Department of Pathology, Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig University, Giessen, Germany
| | - Maria G Frid
- Divisions of Paediatric Critical Care Medicine and Cardiovascular Pulmonary Research, University of Colorado Denver, Denver, CO, USA
| | - Ghazwan Butrous
- Medway School of Pharmacy, University of Kent at Canterbury, Canterbury, UK
| | - Nick W Morrell
- Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Vinicio A de Jesus Perez
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA
| | - David I Stuart
- Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK
| | - Kevin O'Gallagher
- King's College London British Heart Foundation Centre of Excellence, London, UK
| | - Ajay M Shah
- King's College London British Heart Foundation Centre of Excellence, London, UK
| | - Yasmine Aguib
- Aswan Heart Centre, Aswan, Egypt
- National Heart & Lung Institute, Imperial College London, London, UK
| | - Magdi H Yacoub
- Aswan Heart Centre, Aswan, Egypt.
- National Heart & Lung Institute, Imperial College London, London, UK.
- Harefield Heart Science Centre, London, UK.
| |
Collapse
|
|
48
|
Haslak F, Ozbey D, Yildiz M, Adrovic A, Sahin S, Koker O, Aliyeva A, Guliyeva V, Yalcin G, Inanli G, Kocazeybek BS, Kasapcopur O, Barut K. Asymptomatic SARS-CoV-2 seropositivity: patients with childhood-onset rheumatic diseases versus healthy children. Clin Rheumatol 2022; 41:1523-1533. [PMID: 35044502 PMCID: PMC8766358 DOI: 10.1007/s10067-022-06067-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 01/10/2022] [Accepted: 01/13/2022] [Indexed: 12/13/2022]
Abstract
OBJECTIVE We aimed to find out the asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among pediatric patients with rheumatic diseases and healthy children and to compare them with each other. METHODS Patients with familial Mediterranean fever (FMF), juvenile idiopathic arthritis (JIA), and juvenile systemic lupus erythematosus (jSLE) and healthy children as healthy control (HC) group who remained asymptomatic during the pandemic are examined by ELISA immunoglobulin (Ig) A and IgG tests in this cross-sectional study. RESULTS Overall, 149 subjects (90 females) were included in the study. While IgA was positive in 15 subjects (10%) (HC: 8, jSLE: 3, FMF: 2, JIA: 2; p = 0.196), IgG was positive in 14 subjects (9.4%) (HC: 7, JIA: 5, FMF: 1, jSLE: 1; p = 0.156). Nineteen subjects (12.75%) were IgA or IgG positive (HC: 8, JIA: 5, jSLE: 3, FMF: 3; p = 0.644). Although not significant, seropositivity was more often in HC group. Both IgA and IgG positivity were not found to be related to age, sex, underlying rheumatic diseases, and received treatments of the patients. CONCLUSION We revealed that patients with childhood-onset rheumatic diseases, even if they receive immunosuppressive medication such as biologic or conventional disease-modifying anti-rheumatic drugs, might have an asymptomatic SARS-CoV-2 infection, similarly to their healthy peers. Key points • Although it has been already known that children are most likely to have asymptomatic SARS-CoV-2 infection, there is a lack of data on the disease course of children with rheumatic disease. • There was no significant difference regarding the asymptomatic SARS-CoV-2 seropositivity rates between healthy children and the patients with childhood-onset rheumatic diseases. • Patients with childhood-onset rheumatic diseases, even if they receive immunosuppressive medication, might have asymptomatic SARS-CoV-2 infection, similarly to their healthy peers.
Collapse
Affiliation(s)
- Fatih Haslak
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Dogukan Ozbey
- Department of Microbiology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Mehmet Yildiz
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Amra Adrovic
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Sezgin Sahin
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Oya Koker
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Ayten Aliyeva
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Vafa Guliyeva
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Gamze Yalcin
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Gulmelek Inanli
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Bekir S. Kocazeybek
- Department of Microbiology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Ozgur Kasapcopur
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| | - Kenan Barut
- Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa Cerrahpasa Medical School, Istanbul, Turkey
| |
Collapse
|
|
49
|
Liu Z, Kilic G, Li W, Bulut O, Gupta MK, Zhang B, Qi C, Peng H, Tsay HC, Soon CF, Mekonnen YA, Ferreira AV, van der Made CI, van Cranenbroek B, Koenen HJPM, Simonetti E, Diavatopoulos D, de Jonge MI, Müller L, Schaal H, Ostermann PN, Cornberg M, Eiz-Vesper B, van de Veerdonk F, van Crevel R, Joosten LAB, Domínguez-Andrés J, Xu CJ, Netea MG, Li Y. Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19. Front Immunol 2022; 13:838132. [PMID: 35464396 PMCID: PMC9022455 DOI: 10.3389/fimmu.2022.838132] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 03/16/2022] [Indexed: 11/23/2022] Open
Abstract
The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals.
Collapse
Affiliation(s)
- Zhaoli Liu
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Gizem Kilic
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Wenchao Li
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Ozlem Bulut
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Manoj Kumar Gupta
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Bowen Zhang
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Cancan Qi
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - He Peng
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Hsin-Chieh Tsay
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Chai Fen Soon
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Yonatan Ayalew Mekonnen
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany
| | - Anaísa Valido Ferreira
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.,Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Caspar I van der Made
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Bram van Cranenbroek
- Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Hans J P M Koenen
- Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Elles Simonetti
- Laboratory of Pediatric Infectious Diseases, Radboud Centre for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Dimitri Diavatopoulos
- Laboratory of Pediatric Infectious Diseases, Radboud Centre for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Marien I de Jonge
- Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands
| | - Lisa Müller
- Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
| | - Heiner Schaal
- Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
| | - Philipp N Ostermann
- Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
| | - Markus Cornberg
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Britta Eiz-Vesper
- Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, Hannover, Germany
| | - Frank van de Veerdonk
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Leo A B Joosten
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Jorge Domínguez-Andrés
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| | - Cheng-Jian Xu
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.,Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.,Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
| | - Yang Li
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
| |
Collapse
|
|
50
|
Braga CL, Acquarone M, Arona VDC, Osório BS, Barreto TG, Kian RM, Pereira JPAL, Silva MDMCD, Silva BA, de Oliveira GMM, Macedo Rocco PR, Silva PL, Alencar AKN. Can Epigenetics Help Solve the Puzzle Between Concomitant Cardiovascular Injury and Severity of Coronavirus Disease 2019? J Cardiovasc Pharmacol 2022; 79:431-443. [PMID: 34935698 DOI: 10.1097/fjc.0000000000001201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 11/29/2021] [Indexed: 01/08/2023]
Abstract
ABSTRACT The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has significant implications in patients with concomitant cardiovascular disease (CVD) because they are the population at the greatest risk of death. The treatment of such patients and complications may represent a new challenge for the fields of cardiology and pharmacology. Thus, understanding the involvement of this viral infection in CVD might help to reduce the aggressiveness of SARS-CoV-2 in causing multiorgan infection and damage. SARS-CoV-2 disturbs the host epigenome and several epigenetic processes involved in the pathophysiology of COVID-19 that can directly affect the function and structure of the cardiovascular system (CVS). Hence, it would be relevant to identify epigenetic alterations that directly impact CVS physiology after SARS-CoV-2 infection. This could contribute to the view of this virus-induced CVS injury and direct forthcoming tackles for COVID-19 treatment to reduce mortality in patients with CVD. Targeting epigenetic marks could offer strong evidence for the development of novel antiviral therapies, especially in the context of COVID-19-related CVS damage. In this review, we address some of the main signaling pathways that are currently known as being involved in COVID-19 pathophysiology and the importance of this glint on epigenetics and some of its modifiers (epidrugs) to control the unregulated epitope activity in the context of SARS-CoV-2 infection, COVID-19, and underlying CVD.
Collapse
Affiliation(s)
- Cássia L Braga
- Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mariana Acquarone
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Victor da C Arona
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
| | - Brenno S Osório
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
| | - Thiago G Barreto
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
| | - Ruan M Kian
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
| | | | - Marina de Moraes C da Silva
- Serviço de Radiologia do Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bagnólia A Silva
- Programa de Pós-graduação em Produtos Naturais e Sintéticos Bioativos, Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa, Brazil
| | - Gláucia Maria M de Oliveira
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and
| | - Patricia Rieken Macedo Rocco
- Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Pedro Leme Silva
- Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Allan K N Alencar
- Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Faculdade de Medicina de Petrópolis, School Clinic, Petrópolis, Brazil
- Departamento de Ciências Fisiológicas, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| |
Collapse
|