Puzzling out the COVID-19: Therapy targeting HLA-G and HLA-E

Hum Immunol. 2020 Dec;81(12):697-701. doi: 10.1016/j.humimm.2020.10.001. Epub 2020 Oct 7.


SARS-CoV2 might conduce to rapid respiratory complications challenging healthcare systems worldwide. Immunological mechanisms associated to SARS-CoV2 infection are complex and not yet clearly elucidated. Arguments are in favour of a well host-adapted virus. Here I draw a systemic immunological representation linking actual SARS-CoV2 infection literature that hopefully might guide healthcare decisions to treat COVID-19. I suggest HLA-G and HLA-E, non classical HLA class I molecules, in the core of COVID-19 complications. These molecules are powerful in immune tolerance and might inhibit/suppress immune cells functions during SARS-CoV2 infection promoting virus subversion. Dosing soluble forms of these molecules in COVID-19 patients' plasma might help the identification of critical cases. I recommend also developing new SARS-CoV2 therapies based on the use of HLA-G and HLA-E or their specific receptors antibodies in combination with FDA approved therapeutics to combat efficiently COVID-19.

Keywords: COVID-19; HLA-E; HLA-G; NKG2A; SARS-CoV2.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19 / epidemiology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • HLA-E Antigens
  • HLA-G Antigens / immunology*
  • HLA-G Antigens / metabolism
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immune Tolerance
  • Immunization, Passive
  • Molecular Targeted Therapy
  • SARS-CoV-2 / physiology*
  • Signal Transduction / drug effects
  • Virus Internalization
  • Virus Replication


  • Antiviral Agents
  • HLA-G Antigens
  • Histocompatibility Antigens Class I