COVID-19 Is a Multi-Organ Aggressor: Epigenetic and Clinical Marks.

Mankgopo Magdeline Kgatle,Siamon Gordon,Hosana Gomes Rodrigues,Phetole Walter Mahasha,Honest Ndlovu,Jan Rijn Zeevaart,Pedro Moura-Alves,Mariza Vorster,Tebatso Moshoeu Gillian Boshomane,Gabriel Mashabela,Mike Machaba Sathekge,Palesa Caroline Koatale,Ismaheel Opeyemi Lawal

doi:10.3389/fimmu.2021.752380

Abstract

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, and progression.

Highlights

Reviewed by: Sayuri Seki, National Institute of Infectious Diseases (NIID), Japan Sunil Joshi, University of Miami, United States
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
angiotensin-converting enzyme 2 (ACE2) level is low in the capillary endothelial cells of the cerebral circulation, circumstantial evidence suggests that SARS-CoV-2 may access these cells by crossing the blood-brain barrier, as demonstrated by in vitro studies

Summary

MAIN BACKGROUND

Epigenetics is a branch of biology arising from inheritable gene transcription alterations in response to environmental cues, such as pollutants, chemicals, radiation, diet, stress, and pathogenic organisms [1]. ACE2 level is low in the capillary endothelial cells of the cerebral circulation, circumstantial evidence suggests that SARS-CoV-2 may access these cells by crossing the blood-brain barrier, as demonstrated by in vitro studies This may involve unknown indirect mechanisms that may be responsible for clinical manifestation (examples are anosmia, ageusia, and altered mental status) and neurological complications that have been observed in critical cases of COVID-19 infections (Figure 2) [67,68,69,70,71,72,73]. SARS-CoV-2 triggers the activation of the RNA-based pathogen sensors such as TLR3, TLR4, TLR7, and retinoic acid-inducible gene-I-like receptors (RIG-I), which complex with a melanomadifferentiation associated 5 (MDA-5) to establish a frontline defence mechanism [143] This complex is epigenetically subverted to induce abnormally elevated levels of interferons (IFNs) and pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-a) and interleukins (ILs), associated with critically ill and ICU admission of COVID-19 patients [131, 144]. We discuss epigenetic marks and alterations that we hypothesize may play a role in ACE2 receptor regulation and COVID-19 pathogenesis/treatment

Writing of DNA Methylation and Role of DNMTs

Findings

AUTHOR CONTRIBUTIONS