In a recent study published in Epigenetics, researchers investigated epigenetic rewiring of odor perception in coronavirus 2-infected cells (SARS-CoV-2) of severe acute respiratory syndrome.
Study: Epigenetic reconfiguration of pathways related to odor perception in immune cells exposed to SARS-CoV-2 in vivo and in vitro. Image credit: MiniStocker / Shutterstock
Fund
Most people recovering from coronavirus disease 2019 (COVID-19) experience mild to moderate symptoms, while some recovering show no symptoms. Although several studies have shown that viruses such as SARS-CoV-2 evade the immune system through epigenetic pathways, including methylation of deoxyribonucleic acid (DNA), research is needed to understand the importance of these changes in the healthy recovery of people infected with COVID-19. .
About the study
In the present study, the researchers compared epigenomic DNA patterns in convalescent individuals of COVID-19 with those in uninfected controls before and after the COVID-19 pandemic.
The team enrolled participants during the first wave of COVID-19 in Linkoping, Sweden, between May 29, 2020 and July 10, 2020. Eligible participants included people who had recovered from COVID-19 and those who had no history of COVID-19 infection. The team obtained saliva and blood samples from 38 participants belonging to three different cohorts: (1) uninfected controls (Con), including healthy individuals who had no SARS-CoV-2-specific T cell responses or immunoglobulin G (IgG). (2) People convalescent from COVID-19 (CC19) who reported a mild or asymptomatic initial infection showed the presence of SARS-CoV-2-specific IgG antibodies by multiple suspension immunoassay (SMIA) and ( 3) asymptomatic individuals presenting with SARS-CoV. -2-specific T responses (SFT).
Participants responded to self-reported health questionnaires related to COVID-19 symptoms, such as difficulty breathing, headache, fever, cough, muscle aches, fatigue, loss of taste or smell, congestion, or nausea. Questionnaires also collected information on dates for self-reported symptoms, duration between sampling and onset of symptoms, age, gender, height, weight, and medical history.
The team compared DNA patterns across the epigenome in peripheral blood mononuclear cells (PBMCs) found in uninfected controls with those of recovered COVID-19 convalescents and asymptomatic participants who presented responses. of SARS-CoV-2-specific T cells. Variations in DNA methyloma between different cohorts of samples were identified by performing principal component analyzes (PCAs).
Results
The results of the study showed that three major PCs were the major contributors to variations in DNA patterns in the epigenome. The team observed that the components that contributed among CC19 participants were markedly different from those in the Con and SFT cohorts. A total of 87 differentially methylated CpGs (DMCs) were found when comparing CC19 DNA methylomas with Con methylomas. This showed that the DMC signature could efficiently differentiate CC19s from Con and SFT participants, suggesting that a previous SARS-CoV-2 infection could have caused the epigenome variation that persisted for a few months afterwards. of infection recovery.
The team also noted that most CC19 individuals tested positive for the presence of specific SARS-CoV-2 IgG responses in saliva and blood samples. People who tested positive for SARS-CoV-2-specific T cell responses or antibodies to saliva samples while plasma samples tested negative for SARS-CoV-2-specific antibodies showed results similar to those of uninfected control individuals on PCA analyzes.
Pathway overrepresentation analyzes revealed that the two substantially overrepresented pathways were involved in the effect of SARS-CoV-2 infection in CC19 individuals. The use of differentially methylated genes (DMG) 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 intra-network interactions. . In addition, the team observed that genes showing the highest combined centrality scores included HSP90AA1, TP53, INS, and CFTR. Overrepresentation analyzes also showed that the 66 genes in the module were involved in pathways such as signaling of muscarinic acetylcholine receptors 1 and 3, apoptosis signaling, and the gonadotropin-releasing hormone receptor pathway.
The team also found a set of DMCs shared by all cohorts of participants. Overlapping shared DMGs revealed eight different overlapping DMGs. Further network analysis of DMGs superimposed on the in vitro environment resulted in a module consisting of six genes also detected in the in vivo environment.
Conclusion
The study’s findings showed epigenome-wide variations in the DNA patterns of individuals recovered by COVID-19 who had experienced mild to moderate symptoms during their SARS-CoV-2 infection compared with control subjects. not infected. The study indicated that DNA methylation is one of the epigenetic mechanisms affected by SARS-CoV-2 infection. The researchers believe that the present study will serve as a basis for developing effective diagnostic and therapeutic approaches against COVID-19.