Coordinated Loss and Acquisition of NK Cell Surface Markers Accompanied by Generalized Cytokine Dysregulation in COVID-19

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 1996
• Main Authors: Ustiuzhanina, Maria O, Vavilova, Julia D, Boyko, Anna A, Streltsova, Maria A, Kust, Sofya A, Kanevskiy, Leonid M, Sapozhnikov, Alexander M, Iskhakov, Rustam N, Gubernatorova, Ekaterina O, Drutskaya, Marina S, Bychinin, Mikhail V, Zhukova, Oksana A, Novikova, Oksana N, Sotnikova, Anna G, Yusubalieva, Gaukhar M, Baklaushev, Vladimir P, Kovalenko, Elena I
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.01.2023; MDPI
• Subjects: adaptive-like NK cells; CD16 antigen; CD57 antigen; Cell activation; Cell surface; Cells; Coronaviruses; COVID-19; Cytokines; Cytotoxicity; Depletion; Genotype & phenotype; Humans; Immune response; Infections; Killer Cells, Natural; Lymphocytes; Natural killer cells; NK Cell Lectin-Like Receptor Subfamily K; NK cells; NKG2 antigen; Pandemics; PD-1 protein; phenotype; Programmed Cell Death 1 Receptor; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Surface markers; Viral diseases; Viral infections; COVID-19; phenotype; NK cells; SARS-CoV-2; adaptive-like NK cells; coordinative response; cytokines
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24031996

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is accompanied by a dysregulated immune response. In particular, NK cells, involved in the antiviral response, are affected by the infection. This study aimed to investigate circulating NK cells with a focus on their activation, depletion, changes in the surface expression of key receptors, and functional activity during COVID-19, among intensive care unit (ICU) patients, moderately ill patients, and convalescents (CCP). Our data confirmed that NK cell activation in patients with COVID-19 is accompanied by changes in circulating cytokines. The progression of COVID-19 was associated with a coordinated decrease in the proportion of NKG2D and CD16 NK cells, and an increase in PD-1, which indicated their exhaustion. A higher content of NKG2D NK cells distinguished surviving patients from non-survivors in the ICU group. NK cell exhaustion in ICU patients was additionally confirmed by a strong negative correlation of PD-1 and natural cytotoxicity levels. In moderately ill patients and convalescents, correlations were found between the levels of CD57, NKG2C, and NKp30, which may indicate the formation of adaptive NK cells. A reduced NKp30 level was observed in patients with a lethal outcome. Altogether, the phenotypic changes in circulating NK cells of COVID-19 patients suggest that the intense activation of NK cells during SARS-CoV-2 infection, most likely induced by cytokines, is accompanied by NK cell exhaustion, the extent of which may be critical for the disease outcome.