AUTHOR=Jaiswal Sarita Rani , Arunachalam Jaganath , Saifullah Ashraf , Lakhchaura Rohit , Tailor Dhanir , Mehta Anupama , Bhagawati Gitali , Aiyer Hemamalini , Khamar Bakulesh , Malhotra Sanjay V. , Chakrabarti Suparno 

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

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.887230

DOI=10.3389/fimmu.2022.887230

ISSN=1664-3224

ABSTRACT=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 health-care workers following administration of heat killed Mycobacterium w (Mw group) in comparison to a control group.  In both groups, COVID-19 correlated with a lower NKG2C+ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in Mw group (p=0.0009), particularly in those with lower baseline NKG2C expression, along with downregulation of iNK cells (p<0.0001). This translated to a significant reduction in incidence and severity of COVID-19 in the Mw group (IRR-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of ANK pathway genes and an enhanced ANK mediated 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.