m6A Regulator-Mediated Methylation Modification Patterns and Characteristics of Immunity in Blood Leukocytes of COVID-19 Patients

Front Immunol. 2021 Nov 30:12:774776. doi: 10.3389/fimmu.2021.774776. eCollection 2021.

Abstract

Both RNA N6-methyladenosine (m6A) modification of SARS-CoV-2 and immune characteristics of the human body have been reported to play an important role in COVID-19, but how the m6A methylation modification of leukocytes responds to the virus infection remains unknown. Based on the RNA-seq of 126 samples from the GEO database, we disclosed that there is a remarkably higher m6A modification level of blood leukocytes in patients with COVID-19 compared to patients without COVID-19, and this difference was related to CD4+ T cells. Two clusters were identified by unsupervised clustering, m6A cluster A characterized by T cell activation had a higher prognosis than m6A cluster B. Elevated metabolism level, blockage of the immune checkpoint, and lower level of m6A score were observed in m6A cluster B. A protective model was constructed based on nine selected genes and it exhibited an excellent predictive value in COVID-19. Further analysis revealed that the protective score was positively correlated to HFD45 and ventilator-free days, while negatively correlated to SOFA score, APACHE-II score, and crp. Our works systematically depicted a complicated correlation between m6A methylation modification and host lymphocytes in patients infected with SARS-CoV-2 and provided a well-performing model to predict the patients' outcomes.

Keywords: COVID-19; immune characteristics; leukocytes; m6A methylation modification; protective model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • COVID-19 / immunology*
  • COVID-19 / virology*
  • Cluster Analysis
  • Computational Biology / methods
  • Disease Susceptibility / immunology
  • Gene Expression Profiling
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Leukocytes / immunology*
  • Leukocytes / metabolism
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • ROC Curve
  • SARS-CoV-2 / physiology*

Substances

  • RNA, Viral
  • N(6)-methoxyadenosine
  • Adenosine