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Authors:Christopher Maucourant et al.,  

Journal/ Pre-Print:medRxiv 

Tags: Immunology/Immunity, Clinical 

Research Highlights  

  1. NK cells are activated in moderate and severe COVID-19 disease. 

  1. Adaptive NK cell expansions associate with severe COVID-19 disease 

  1. CD56bright NK cell cytotoxicity is associate with COVID-19 disease severity. 

Summary  

The study characterized NK cell subsets in a cohort of 27 hospitalized patients with moderate or severe COVID-19 and 17 healthy volunteers in Karolinska University, Sweden. the absolute count of total NK cells and the CD56dim and CD56bright subsets was  

reduced in patients compared to controls. Higher frequency of activated NK cells was observed in peripheral blood of COVID-19 patients compared to healthy controls, and that could be corroborated in analysis of NK cells from BAL fluid of COVID-19 patients. Moderate and severe patients displayed similar activation profile, suggesting NK activation is not associated with disease severity. Analysis of NK cell education (via inhibitory KIRs or NKG2A expression) revealed that NK responses in acute COVID-19 occurred independently of  

NK cell education status. Further analysis of NK subsets showed that severbut not moderate, COVID-19 disease is associated with a high presence of adaptive NK cell expansions. Indeed, unsupervised analysis of NK cell phenotypes showed a NK cluster enriched with adaptive features associated with disease severity. In addition to adaptive NK cells, clinical laboratory parameters were correlated with CD56bright cytotoxicity. Thus, there is strong association between arming of NK cells and disease severity, which is coupled with IL-6 levels but also with several clinical disease severity scores.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19 

Study Type  

  • Clinical Cohort study 

Strengths and limitations of the paper 

Novelty: The study provides a detailed phenotypic analysis of NK cellin COVID-19 disease, linking specific NK subsets with disease severity. 

Standing in the field: Declining of peripheral blood NK cells and phenotypic alterations in patients with COVID-19 have been reported in other studies (Wilk, A. J. et al. Nat Med2020& Giamarellos-Bourboulis, E. J. et al. Cell Host Microbe,2020). The study supports previous findings.  

Appropriate statistics: Yes 

Viral model used:SARS-CoV-2  

Translatability: The study gives an insight for the role of NK cells in patients with COVID-19.  

Main limitations:  

  1. The authors suggest that expansion of adaptive NK cells is correlated with disease severity. The CMV status was considered in the study but the figures included both CMV+ and CMV- patients. Comparing the size of NK adaptive populations in only CNV seropositive patients across the group will support the conclusion.  

  1. Minimal analysis for CD56neg NK subset which has been reported to increase in their frequency in COVID-19 patients (Ana Marcos-Jiménez1 et.al 2020) and in other viral infections.  

  1. For immunophenotype analysis, cluster 24 as well as cluster 21 were shown to be associated with moderate infection. While greater details were provided for cluster 21 in figure 4, minimal discussion was included for cluster 24.