BACKGROUND: NK cells, alone with T lymphocytes, have a high antiviral activity. Exploring the contribution of NK cells in fighting SARS-CoV-2 infection may promote the development of appropriate treatments for COVID-19. Previously, NK cell response was considered nonspecific, provided by a combination of signals from activating and inhibitory receptors. Currently, the existence of certain subpopulations of antigen-specific, or adaptive, NK cells has been shown.AIM: To evaluate the functional response of NK cells induced by SARS-CoV-2 peptides.MATERIALS AND METHODS: The functional response of NK cells to SARS-CoV-2 peptides was determined by their degranulation (surface CD107a expression) and IFNγ production levels, and by the activation degree (HLA-DR expression level). Volunteers who recovered from COVID-19 participated in the study, and immune cells from a healthy volunteer without SARS-CoV-2-specific antibodies were used as controls.RESULTS: NK cells from individuals who had recovered from COVID-19, in contrast to a donor who had not been infected, showed a higher level of IFNγ production in response to SARS-CoV-2 peptides, compared with control samples. The level of degranulation of NK cells from donors previously infected with SARS-CoV-2 was higher than in the corresponding control. The proportion of activated NK cells obtained from recovered donors was also higher in samples stimulated with SARS-CoV-2 peptides.CONCLUSIONS: We have demonstrated the activation of NK cells obtained from people who had previously recovered from COVID-19 in response to SARS-CoV-2 peptide antigens in cultures of peripheral mononuclear cells in vitro. This study reveals the possibility for further investigation of antigen-specific NK cells in COVID-19 disease. The use of such cells could help develop treatments for SARS-CoV-2 infection.