Epigenetic factors predicting disease severity COVID-19

This epigenome-wide association study (EWAS) demonstrates that the epigenetic endowment of each individual influences the severity of COVID-19 disease

Description of the Study:

  • Title: Epigenome-wide association study of COVID-19 severity with respiratory failure.
  • Principal Investigators: Manel Esteller, Aurora Pujol, Manuel Castro de Moura,Veronica Davalos, Laura Planas Serra, Damiana Alvarez Errico, Carles Arribas, Montserrat Ruiz and et al.
  • Centers of Implementation: Fourteen Hospitals in Spain.
  • Study Population: 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.7%) of whom had mild symptomatology that did not involve hospitalization and 213 (52.3%) had a severe clinical course that required respiratory support.
  • Study Type: Epigenome-wide association study (EWAS)
  • Design: The set of cases was divided into discovery (n = 207) and validation (n = 200) cohorts, balanced for age and sex of individuals. We analysed the DNA methylation status of 850,000 CpG sites in these patients.
  • Methods: Whole blood samples and clinical data from the study population were collected between March 7th 2020 and September 14th 2020.

Objectives of the Study:

Principal Objective: To identify candidate DNA methylation loci linked to the severity of the disease, particularly with respect to respiratory failure.

More about this Study:

Background: COVID-19 has a wide spectrum of clinical manifestations, with the majority of infected subjects showing only mild symptoms or being asymptomatic. The principal group of patients with high mortality rates comprises those with severe respiratory failure associated with acute respiratory distress syndrome (ARDS) and interstitial pneumonia.

Epigenetics, defined as the study of changes in gene function that are heritable and that do not entail a change in DNA sequence, plays a major role in tissue homoeostasis.

Most importantly, in the case of COVID-19, the recognition that the activity of the adaptive immune system, including that of B- and T-cells, is significant for the provision of pre-existing immunity to SARS-CoV-2. This means that epigenetic modification is a potentially powerful mechanism that determines the development of severe symptoms. In this regard, the DNA methylation landscape is central to the homoeostasis of the immune system.

Added value: The findings of this study demonstrate the existence of differential DNA methylation sites that distinguish COVID-19 patients with paucisymptomatic clinical status from those who will require hospitalized oxygen therapy, including mechanical ventilation and additional organ support measures. The epigenetic loci identified were mostly located within genes associated with the interferon response pathway. Using these DNA methylation biomarkers, we obtained an epigenomic signature that we have called “EPICOVID” that showed great accuracy in predicting COVID-19 severity.


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