High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection

Elizabeth K Graydon; Allison M W Malloy; Kawthar Machmach; Peifang Sun; Dominic Paquin-Proulx; Stephen Lizewski; Rhonda Lizewski; Dawn L Weir; Carl W Goforth; Stephen K Anderson; Andrew G Letizia; Edward Mitre

doi:10.1016/j.crimmu.2023.100064

High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection

Curr Res Immunol. 2023 Jul 15:4:100064. doi: 10.1016/j.crimmu.2023.100064. eCollection 2023.

Authors

Elizabeth K Graydon^{1

2}, Allison M W Malloy³, Kawthar Machmach^{2

4

5}, Peifang Sun⁶, Dominic Paquin-Proulx^{2

4

5}, Stephen Lizewski⁷, Rhonda Lizewski⁸, Dawn L Weir⁶, Carl W Goforth⁶, Stephen K Anderson⁹, Andrew G Letizia⁶, Edward Mitre¹

Affiliations

¹ Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
³ Department of Pediatrics, Uniformed Services University, Bethesda, MD, USA.
⁴ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring MD, USA.
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Infectious Disease Directorate, Naval Medical Research Center, Silver Spring, MD, USA.
⁷ Navy Medical Research Center, Silver Spring, MD, USA.
⁸ Bureau of Medicine and Surgery, Arlington, VA, USA.
⁹ Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Abstract

This study tested the hypothesis that high frequencies of natural killer (NK) cells are protective against symptomatic SARS-CoV-2 infection. Samples were utilized from the COVID-19 Health Action Response for Marines study, a prospective, observational study of SARS-CoV-2 infection in which participants were enrolled prior to infection and then serially monitored for development of symptomatic or asymptomatic infection. Frequencies and phenotypes of NK cells (CD3^-CD14^-CD19^-CD56⁺) were assessed by flow cytometry. Individuals that developed asymptomatic infections were found to have higher pre-infection frequencies of total NK cells compared to symptomatic individuals (10.61% [SD 4.5] vs 8.33% [SD 4.6], p = 0.011). Circulating total NK cells decreased over the course of infection, reaching a nadir at 4 weeks, while immature NK cells increased, a finding confirmed by multidimensional reduction analysis. These results indicate that NK cells likely play a key role in controlling the severity of clinical illness in individuals infected with SARS-CoV-2.

Keywords: Asymptomatic; NK cells; Natural killer cells; SARS-CoV-2; Symptomatic.