Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19

Front Immunol. 2022 May 4;13:887230. doi: 10.3389/fimmu.2022.887230. eCollection 2022.


The kinetics of NKG2C+ adaptive natural killer (ANK) cells and NKG2A+inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare workers following the administration of the heat-killed Mycobacterium w (Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C+ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in the Mw group (p=0.0009), particularly in those with a lower baseline NKG2C expression, along with the downregulation of iNK cells (p<0.0001). This translated to a significant reduction in the incidence and severity of COVID-19 in the Mw group (incidence risk ratio-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of the ANK pathway genes and an enhanced ANK-mediated antibody-dependent cellular cytotoxicity (ADCC) signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.

Keywords: ADCC; COVID-19; Mw for COVID-19 Mycobacterium w (Mw); NKG2A; NKG2C; SARS-CoV-2; adaptive NK cells; innate immunity.

MeSH terms

  • COVID-19*
  • Humans
  • Killer Cells, Natural
  • Mycobacterium*
  • NK Cell Lectin-Like Receptor Subfamily C
  • SARS-CoV-2


  • NK Cell Lectin-Like Receptor Subfamily C