HLA-E regulation of NK cell response in SARS-CoV-2 infection

Functional impairment of Natural killer (NK) cells has been related to COVID19 severity. On the other hand, HLA-E is one of the main regulators of NK cell function thanks to its interaction with two NK cell receptors, NKG2A and NKG2C. We used samples from SARS-CoV-2 uninfected and infected individuals, developing mild and severe form of COVID19, to study the relationship between HLA-E expression, NK cell phenotype, NKG2X expression, effector functions and severity of COVID-19. Our results show that increased HLA-E levels in severe COVID-19 patients was associated with NK cell exhaustion, reversion of the NKG2A/NKG2C ratio and reduced NK cell response when stimulated through HLA-E/NKG2X axis. SARS-CoV-2 infection was also linked to a loss of the CD56bright and CD56dim subsets, while CD56neg and adaptive NK cells were augmented, especially in people with severe forms of the disease.