COVID-19 Epigenetics and Implications for Public Health (original) (raw)
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Environmental Science and Pollution Research
COVID-19 pandemic waves hitting worldwide result in drastic postinfection complications with interindividual variations, which raised the question for the cause of these observed variations. This urged to think "the impact of environment-affected genes"? In an attempt to unravel the impact of environment-affected genes, a systematic rapid review was conducted to study "the impact of host or viral epigenetic modulation on COVID-19 infection susceptibility and/or outcome." Electronic databases including Web of Science, SCOPUS, Cochrane Central Register of Controlled Trials, PubMed, and Google Scholar, and other databases were searched. The search strings included "COVID-19" OR "SARS-CoV-2" AND (Epigenetics'). Articles with randomized clinical trials (RCTs) and observational study designs, conducted on humans and available in the English language, were selected, with respect to "The interplay between the SARS-CoV-2 virus and Epigenetics" published from 2020 to February 2021 (but not limited to 2020, being expanded to 2015). Database search yielded 1330 articles; after screening, exclusion, and further filtrations, 51 articles were included. Susceptibility to COVID-19 infection is related to the viral-microRNAs (miRNAs) which alter virulence of the transmitted SARS-CoV-2 strains and impact host-miRNA-related innate immunity. Host-DNA methylation and/or chromatin remodeling may be implicated in severe cytokine storm that can ultimately results in fatal outcome.
European Journal of Medical Research
Background COVID-19 has a wide spectrum of clinical manifestations and given its impact on morbidity and mortality, there is an unmet medical need to discover endogenous cellular and molecular biomarkers that predict the expected clinical course of the disease. Recently, epigenetics and especially DNA methylation have been pointed out as a promising tool for outcome prediction in several diseases. Methods and results Using the Illumina Infinium Methylation EPIC BeadChip850K, we investigated genome-wide differences in DNA methylation in an Italian Cohort of patients with comorbidities and compared severe (n = 64) and mild (123) prognosis. Results showed that the epigenetic signature, already present at the time of Hospital admission, can significantly predict risk of severe outcomes. Further analyses provided evidence of an association between age acceleration and a severe prognosis after COVID-19 infection. The burden of Stochastic Epigenetic Mutation (SEMs) has been significantly i...
Pharmaceutical and Biomedical Research
Background: There is an intense search for the Coronavirus Disease 19 (COVID-19) cure, to stem the spread and burden of the disease worldwide. Studies revealed that epigenetic modifications impact the pathogenesis of some COVID-19 cases, which can be used as therapeutic targets. Objectives: This review articulated the role of epigenetics in the pathogenesis and management of COVID-19. Methods: Relevant articles published between January 2000 and November 2020 were retrieved from reputable academic databases, including PubMed, SpringerLink, Scopus, and Google Scholar. Results: Epigenetic modifications in the COVID-19’s pathogen, called the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and host’s cells may influence susceptibility or resistance to the disease. Notably, abnormal Deoxyribonucleic Acid (DNA) methylation and histone modification involving immune regulatory genes and molecules, such as cytokines and interferon-regulated genes may compromise immune function ...
COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks
Frontiers in Immunology, 2021
The progression of coronavirus disease 2019 (COVID-19), resulting from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be influenced by both genetic and environmental factors. Several viruses hijack the host genome machinery for their own advantage and survival, and similar phenomena might occur upon SARS-CoV-2 infection. Severe cases of COVID-19 may be driven by metabolic and epigenetic driven mechanisms, including DNA methylation and histone/chromatin alterations. These epigenetic phenomena may respond to enhanced viral replication and mediate persistent long-term infection and clinical phenotypes associated with severe COVID-19 cases and fatalities. Understanding the epigenetic events involved, and their clinical significance, may provide novel insights valuable for the therapeutic control and management of the COVID-19 pandemic. This review highlights different epigenetic marks potentially associated with COVID-19 development, clinical manifestation...
A New Perspective of COVID-19 Infection: An Epigenetics Point of View
Global Medical Genetics, 2021
Coronavirus disease 2019 (COVID-2019) started in Wuhan, China, in December 2019. Angiotensin-converting enzyme 2 (ACE2) receptor was one of the most important genes related to the entrance of the virus to the host. Until now, several variations have been identified in ACE2 and related transmembrane protease serine 2. Epigenetic modifications not only play an important role during the maintenance of genome and cellular homoeostasis but also for the etiopathophysiology of the virus infection. Studies showed methylation of ACE2 was changed to depend on host and age of the host during the viral infection.In this study, we provided an epigenetics point of view to the coronavirus infection. We highlight the importance of epigenetic modifications during viral replication and infection and their interaction with COVID-19 susceptibility and host viral response.
Infection, 2023
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.
Major epigenetic factors associated with the novel coronavirus disease-2019 (COVID-19) severity
2021
The worldwide spread and high rate of viral transmission and related morbidity and mortality of Coronavirus disease-19 (COVID-19) is a crisis. Some epigenetic determinants predispose individuals to severe infection. Patients with prior chronic medical illnesses (hypertension, diabetes, lupus, and chronic obstructive lung disease) are highly susceptible to the infection. The aging and diabetes pandemic possibly exacerbate the COVID-19 or SARS-CoV-2 pandemic by enhancing COVID-19 associated comorbidities. COVID-19 utilizes several proteins for tackling the host immune response associated with enhancing comorbidities. The angiotensin-converting enzyme (ACE) is a significant receptor for SARS-CoV-2, which significantly expresses higher among individuals with comorbidities and under stress conditions. Patients with systemic lupus erythematosus are also prone to be susceptible to the disease. Viral infections cause a defect in the DNA methylation in lupus, causing further ACE2 hypomethylation and overexpression, leading to viral binding and cytokine storm and tissue damage during COVID-19 infection. The microRNAs (miRNAs) epigenetics regulations also play a critical role in the suppression of immune responses. Meanwhile, viral proteins interplays with the host cell are conferred primarily through TGF-β and HIF-1 signaling, endocytosis, autophagy, and Toll-like receptor signaling RIG-I signaling, Il-17 signaling, and fatty acid oxidation/degradation. Furthermore, the COVID19 patient's metabolic states determine the infection severity. Noticeably, ten human metabolic proteins, including SGTA, SPECC1, FGL2, PHB, STAT3, BCL2L1, CAV1, JUN, PPP1CA, and XPO1, interact with the SARSE-CoV-2. Interactions between SARSCoV's spike protein-containing lipid-rich membrane compartments and epigenetic modulations are considered targets to inhibit the viral infection. Therefore, it seems that epigenetics plays a substantial role in the COVID-19 severity. Future in-depth studies will be promising. Vaccine design, particularly regarding ACE viral receptor monoclonal antibodies, is a proposal alongside adhering to personal hygiene.
Epigenetic Mechanisms Underlying COVID-19 Pathogenesis
Biomedicines
In 2019, a novel severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported and was declared a pandemic by the World Health Organization (WHO) in March 2020. With the advancing development of COVID-19 vaccines and their administration globally, it is expected that COVID-19 will converge in the future; however, the situation remains unpredictable because of a series of reports regarding SARS-CoV-2 variants. Currently, there are still few specific effective treatments for COVID-19, as many unanswered questions remain regarding the pathogenic mechanism of COVID-19. Continued elucidation of COVID-19 pathogenic mechanisms is a matter of global importance. In this regard, recent reports have suggested that epigenetics plays an important role; for instance, the expression of angiotensin I converting enzyme 2 (ACE2) receptor, an important factor in human infection with SARS-CoV-2, is epig...
Epigenetic Study as a New Approach for Therapeutics and Biomarker of Atherosclerosis in COVID-19
Journal of Widya Medika Junior
Introduction : Coronavirus disease 2019 (COVID-19) has affected more than 105 million people globally and resulted in at least 2.3 million deaths. Covid-19 has highlighted the vulnerability of aging populations to emerging diseases. This susceptibility to disease and death is also a major challenge for the development of vaccines and immunotherapeutic agents. Atherosclerosis is one of the main cardiovascular disease, and this disease is one of the most common comorbid diseases affected by Covid-19 and is associated with increased risk of mortality. Biomarker are crucial in decision-making in order to facilitate efficient resource allocation. Recently many researcher develop several biomarker as a new approach in epigenetic area. The discovery of new therapeutic targets as well as biomarkers using epigenetic studies may increase its clinical usefulness. Methods: In this narrative review, a search was carried out with the help of several search engines that match the criteria, namely ...
Epigenomics, 2021
Epigenomics is the collective study of all epigenetic modifications that can affect the genome, the most pivotal of which are DNA methylation (DNAm), histone modifications (e.g., acetylation, citrullination and phosphorylation) and nucleosome remodeling. The latter refers to the dynamic reorganization in the spatial arrangement of chromatin by means of repositioning the nucleosomes, which are short segments of DNA, consisting of approximately 200 base pairs, coiled around eight histone proteins. The resulting alterations in the structure of these bead-like complexes may favor or oppose transcription, determining the course of disease pathogenesis [1], such as coronavirus disease 2019 (COVID-19). Known to correlate inversely with gene expression, DNAm might be associated with increased susceptibility of the pulmonary tissue to COVID-19 [2] and a higher predisposition to this viral disease in patients with pancreatic [3] and prostate cancer [4]. A lesser known epigenetic mechanism, 'X inactivation' is thought to be connected with the function of innate immunity against COVID-19, particularly in male patients [5]. Furthermore, immunity is also influenced by the extensively diverse histone modifications, especially histone citrullination [6]. Nucleosome remodeling, mediated by contextually important proteins such as SMARCA4 and SMAD3, is another epigenetic mechanism that can affect the course of disease, assuming a patient-wise unfavorable role in the case of COVID-19 [7]. The footprint of epigenomics can even be traced back to prenatal life, when developmentally crucial genes such as PEG10 and ECE1, can be affected by DNAm in response to maternal COVID-19 [8], indicating the overall significance of epigenetics in the recent viral pandemic. COVID-19: unwelcome infection facilitated by epigenetic modifications A consequence of SARS coronavirus 2 (SARS-CoV-2) infection, COVID-19 is perhaps the greatest health issue of the century, affecting more than 45 million individuals, with a global death toll exceeding one million [7]. The recent, less-anticipated advent of novel SARS-CoV-2 variants with altered Spike proteins, including the strain with 'Spike N453Y' mutation reported in Netherlands and Denmark; and the more overwhelming variants with 'Spike D614G' and 'N501Y' mutations spreading in England, has caused concerns regarding the efficacy of the recently approved vaccines in the future. The N501Y variant, in particular, has been suggested to be 56% more transmissible, owing to the enhanced binding affinity of the Spike protein to its polypeptide receptor, ACE2, on the host cell [9]; a finding with potential epigenetic implications. Containing a positive-sense ssRNA, SARS-CoV-2 is an enveloped β-coronavirus coated with Spike protein on its surface, which relies on the interaction between this protein and the transmembrane ACE2 on the host cell for viral entry. The epigenetic modifications, especially DNAm, regulating the expression of ACE2 had been known well before the emergence of SARS-CoV-2 [2]. Nonetheless, the rising prominence of epigenomics in the expansive research field of COVID-19 is not solely due to the role of ACE2 in the pathophysiology of the disease, as 332 human proteins have recently been identified to interact with SARS-CoV-2 proteins in several ways. A noteworthy example is HDAC2, which is involved in the initiation of immune responses against viruses [10]. HDAC2 contains a cleavage site that can be targeted by NSP5, Epigenomics