DNA methylation signatures can function somewhat like a fortune teller’s crystal ball – foretelling those patients with poor prognosis and helping to choose the optimal treatment strategy. By gazing into the crystal ball of the COVID-19 methylome, a fortune-telling team led by Manel Esteller (Josep Carreras Leukaemia Research Institute, Barcelona, Spain) and Aurora Pujol (Bellvitge Biomedical Research Institute) have now come forth with a vision of using DNA methylation to predict COVID-19 severity.
Specifically, this team of molecular clairvoyants made use of EPIC arrays to profile DNA methylation from the blood of 407 confirmed COVID-19 patients (under the age of 65) of varying severity. Fascinatingly, they then employed this data to establish a novel DNA methylation signature that associates with disease severity, particularly with respect to respiratory failure.
Rather than gazing into a crystal ball for hazy glimpses, read all the pertinent details from this fascinating study from Castro de Moura, Davalos, and colleagues here:
- 44 CpG sites associated with the complete continuum of COVID-19 severity
- The full spectrum ranges from asymptomatic COVID-19 patients to those with mild symptomatology and those requiring mechanical ventilation and additional support for other organs
- Around 50% of the CpGs locate to twenty coding genes involved in interferon-related pathways (involving innate and adaptive immunity), from interleukin and chemokine activity and viral response networks to the major histocompatibility and inflammasome complexes
- Important genes include the inflammasome component Absent in Melanoma 2 (AIM2) and the Major Histocompatibility Complex, class I C (HLA-C), whose overexpression can induce autoimmune reactions and the excessive cytokine release that exacerbates immune response (as observed in COVID-19)
- These data supported the development of a novel DNA methylation signature named “EPICOVID,” which displays high-level accuracy in predicting COVID-19 severity
- EPICOVID can identify those patients with an epigenomic background associated with severe disease progression for special care, such as early vaccination
Overall, the delineation of a novel DNA methylation signature that predicts COVID-19 severity may significantly impact the clinical management of a disease with a devastating impact on some patients, thereby improving patient outcomes and providing respite to healthcare systems worldwide. Senior author Manel Esteller shares, “Interestingly, 13% of the world population presents this epigenetic signature (EPICOVID), thus, this is the group at maximum risk that we must take special care of.”
For more on how DNA methylation may help to predict those patients with a risk of developing severe COVID-19, head over to EBioMedicine, April 2021.