Epigenome-wide DNA methylation pattern in convalescent COVID-19 subjects

In a recent study published in EpigeneticsResearchers investigated the epigenetic rewiring of odor perception in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

Most Coronavirus Disease 2019 (COVID-19)-Recovered individuals experience mild to moderate symptoms, but some recoverers do not. Various studies have shown that viruses such as SARS-CoV-2 evade the immune system via epigenetic pathways involving deoxyribonucleic acid (DNA) methylation, but infect COVID-19. Research is needed to understand the importance of these modifications in the healthy recovery of individuals who have had the disease. ..

About research

In this study, researchers compared the epigenome DNA patterns of individuals in the COVID-19 convalescent phase with the DNA patterns of non-infected controls before and after the COVID-19 pandemic.

The team registered participants during the first COVID-19 wave in Linköping, Sweden, from May 29, 2020 to July 10, 2020. Eligible participants included those who recovered from COVID-19 and those who had no history of COVID-19 infection. The team obtained saliva and blood samples from 38 participants from three different cohorts: (1) Non-infected controls (Con), including healthy individuals who are not SARS-CoV-2 specific. T cells Alternatively, COVID-19 convalescent individuals (CC19) who reported an immunoglobulin G (IgG) response, (2) mild or asymptomatic initial infection, used SARS-CoV- using the Suspension Multiplex Immunoassay (SMIA). The presence of an IgG antibody specific to 2 was shown. 3) Asymptomatic individuals with SARS-CoV-2 specific T (SFT) response.

Participants completed a health questionnaire related to self-assessment COVID-19 SymptomsIncludes shortness of breath, headache, fever, cough, muscle aches, malaise, loss of taste and smell, congestion, or nausea. The questionnaire also collected information on the dates corresponding to self-reported symptoms, the time between sampling and onset of symptoms, age, gender, height, weight, and medical history.

The team analyzed the DNA pattern of the entire epigenome of peripheral blood mononuclear cells (PBMC) found in non-infected controls, the DNA pattern of recovered COVID-19 recoverers, and the T-cell response specific to SARS-CoV-2. We compared the DNA patterns of the asymptomatic participants shown. Principal component analysis (PCA) was performed to identify changes in DNA methylome between different sample cohorts.

result

Research results have shown that the three major PCs are the major contributors to variations within the DNA pattern of the entire epigenome. The team observed that the contributions of CC19 participants were significantly different from the components of the Con and SFT cohorts. Comparing CC19 DNA methylome with Con methylome, a total of 87 different methylated CpG (DMC) were found. This indicates that the DMC signature can efficiently distinguish CC19 from Con and SFT participants, suggesting that previous SARS-CoV-2 infection may have led to epigenome changes that persisted for months after recovery from infection. It suggests that there is.

The team also noted that most individuals with CC19 tested positive for the presence of SARS-CoV-2 specific IgG responses in saliva and blood samples. Individuals tested positive for SARS-CoV-2 specific T cell response or antibody in saliva samples, whereas negative for SARS-CoV-2 specific antibodies in plasma samples were infected by PCA analysis. The results were similar to those of the non-control.

Overexpression analysis of the pathway revealed that two substantially overexpressed pathways are involved in the effects of SARS-CoV-2 infection on CC19 individuals. Using differentially methylated genes (DMGs) to identify modules induced by SARS-CoV-2 infection, the resulting modules contained 66 genes belonging to protein-protein interactions, 139. Genes have been shown to be derived from intra-network interactions. In addition, the team observed that the genes with the highest complex centrality scores included HSP90AA1, TP53, INS, and CFTR. Overexpression analysis also showed that 66 modular genes are involved in pathways such as muscarinic acetylcholine receptor 1 and 3 signaling, apoptosis signaling, and the gonadotropin-releasing hormone receptor pathway.

The team also found a set of DMCs shared by all participant cohorts. The overlap of shared DMGs reveals eight different overlapping DMGs.Further network analysis of duplicate DMGs in In vitro The environment has resulted in a module containing 6 genes. In vivo setting.

Conclusion

The study results showed epigenome-wide changes in the DNA pattern of COVID-19 recoverers who experienced mild to moderate symptoms through SARS-CoV-2 infection compared to uninfected control subjects. This study showed that DNA methylation is one of the epigenetic mechanisms affected by SARS-CoV-2 infection. Researchers believe that this study serves as the basis for developing effective diagnostic and therapeutic approaches to COVID-19.