BREAKING! Swedish Study Shows That SARS-CoV-2 Causes Epigenetic Changes To Various Genes In Human Host!
A new study by researchers from Linköping University-Sweden has alarmingly discovered that the SARS-CoV-2 coronavirus causes epigenetic changes to a variety of human host genes and that these changes persist way after a person has so called ‘recovered’ from the infections.
The implications of this finding is worrisome as these genes that have undergone epigenetic changes may the factors that are contributing to some of the various manifestations seen in Long COVID currently and also to more health deteriorations that we will see over time and will also increase risks of mortality.
This study further adds more evidence to Thailand Medical News
hypothesis that most exposed to the SARS-CoV-2 coronavirus will have shortened lifespans and will have only between 5 to 8 years left. This can however be even shortened by repeated reinfections with various new emerging SARS-CoV-2 variants! https://www.thailandmedical.news/news/breaking-hypothesis-that-majority-exposed-to-sars-cov-2-will-have-shortened-lifespans-validated-by-study-showing-nsp2-impairs-human-4ehp-gigyf2-comple
It has been found that a majority of SARS-CoV-2 recoverees develop only mild-to-moderate symptoms, while some remain completely asymptomatic.
Despite the fact that it is known that many viruses, including SARS-CoV-2, may evade host immune responses by epigenetic mechanisms including DNA methylation, little is known about whether these modifications can disrupt the immune system and healthy recovery from COVID-19 in the host.
The study team compared epigenome-wide DNA methylation patterns from COVID-19 convalescents with uninfected controls from before and after the pandemic.
Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents, and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2.
Next, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation, and module identification analyses. Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model.
A SARS-CoV-2-induced module was identified in vivo, comprising 66 genes of which six (TP53, INS, HSPA4, SP1, ESR1, and FAS) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signaling, and gonadotropin-releasing hormone receptor pathways.
Also, it was found that numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome.
Alarmingly, the study findings showed that altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. Both in vitro and in vivo exposure caused epigenetic modulation of pathw
ays that also affect odour perception. Future studies should determine whether this reflects host-induced protective antiviral defense or targeted viral hijacking to evade host defense.
The study findings were published in the peer reviewed journal: Epigenetics.
The study team had initially plan to only focus on investigating the epigenetic rewiring of odor perception in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells.
Although various studies have shown that viruses like SARS-CoV-2 evade the immune system via epigenetic pathways, including deoxyribonucleic acid (DNA) methylation, research is needed to understand the importance of these modifications in the healthy recovery of individuals infected with COVID-19.
The study team compared the epigenomic DNA patterns in COVID-19 convalescent individuals to those in uninfected controls before and after the COVID-19 pandemic.
The study team enrolled participants during the first COVID-19 wave in Linkoping, Sweden, between 29 May 2020 and 10 July 2020. The eligible participants included persons who had recovered from COVID-19 and those with no history of a COVID-19 infection.
The research team obtained saliva and blood samples from 38 participants belonging to three distinct cohorts: (1) non-infected controls (Con) including healthy individuals who had neither SARS-CoV-2-specific T-cell or immunoglobulin G (IgG) responses, (2) COVID-19 convalescent persons (CC19) who reported either mild or asymptomatic initial infection showed the presence of IgG antibodies specific to SARS-CoV-2 using suspension multiplex immunoassay (SMIA), and (3) asymptomatic individuals displaying SARS-CoV-2-specific T (SFT) responses.
All research participant answered health questionnaires related to self-reported COVID-19 symptoms, including shortness of breath, headache, fever, cough, muscle pain, fatigue, loss of taste or smell, congestion, or nausea.
The research questionnaires also collected information regarding the dates corresponding to the self-reported symptoms, duration between sampling and symptom onset, age, gender, height, weight, and medical history.
The study team then compared the DNA patterns across the epigenome in peripheral blood mononuclear cells (PBMC) found in non-infected controls to those in recovered COVID-19 convalescent persons and from asymptomatic participants who presented T cell responses specific to SARS-CoV-2. The variations in the DNA methylome among the different sample cohorts were identified by performing principal component analyses (PCA).
The research findings showed that three principal PCs were the major contributors to the variations within DNA patterns across the epigenome.
It was found that the contributing components among the CC19 participants were remarkably different from those in the Con and SFT cohorts.
In all, a total of 87 distinct differentially methylated CpGs (DMCs) were found in comparing CC19 DNA methylomes to the Con methylomes.
Interestingly, this showed that the DMC signature could efficiently differentiate the CC19s from the Con and SFT participants, suggesting that a previous SARS-CoV-2 infection might have led to the variation in the epigenome that persisted for a few months after recovery from the infection.
The study findings also showed that most of the CC19 individuals tested positive for the presence of SARS-CoV-2-specific IgG responses in the saliva as well as blood samples. Individuals who tested positive for SARS-CoV-2-specific T cell responses or antibodies in the saliva samples while the plasma samples tested negative for SARS-CoV-2-specific antibodies displayed results similar to those in uninfected control persons in the PCA analyses.
Importantly, over-representation analyses of pathways revealed that the two substantially over-represented pathways were involved in the effect of SARS-CoV-2 infection on CC19 individuals.
Utilizing the differentially methylated genes (DMGs) to identify modules induced by SARS-CoV-2 infection showed that the resulting modules comprised 66 genes belonging to the protein-protein interaction while 139 genes were from the intra-network interactions.
The study findings showed that the genes displaying the highest combined centrality scores included HSP90AA1, TP53, INS, and CFTR.
Note that some of these genes are involved in very critical pathways in the human body including cancer and tumor control!
Worryingly, the over-representation analyses also showed that the 66 module genes were involved in pathways such as the signaling of muscarinic acetylcholine receptors 1 and 3, apoptosis signaling, and gonadotropin-releasing hormone receptor pathway.
The study team also found a set of DMCs shared by all the participant cohorts.
This overlap of the shared DMGs revealed eight distinct overlapping DMGs.
Subsequent network analysis of the overlapped DMGs in the in vitro environment resulted in a module comprising six genes also detected in the in vivo setting.
Alarmingly, the whole study findings provided evidence of epigenome-wide variations in the DNA patterns of COVID-19-recovered individuals who had experienced mild to moderate symptoms throughout their SARS-CoV-2 infection compared to non-infected control subjects.
The research findings indicated that DNA methylation is one of the epigenetic mechanisms affected by SARS-CoV-2 infection.
The study findings have serious implications for Long COVID and also other serious medical conditions arising in the future and increased risk of mortality for all who have been exposed to the SARS-CoV-2 virus.
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