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. 2023 Mar 14:10.2217/fvl-2022-0040. doi: 10.2217/fvl-2022-0040

Table 1. A summary of studies on NK cells in COVID-19.

Title
Sample
Sample Size
Results
Ref.
Frequency
Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia
PB
60 P, 245 HC
NK cells in COVID-19 patients were significantly lower compared with HC. In severe cases, the number of NK cells was also lower than in patients in a mild situation
[19]
Impaired NK cell counts and cytolytic activity in patients with severe COVID-19
PB
10 P, 78 HC
Impaired NK cell counts and their cytolytic activity was observed in COVID-19 patients compared with HC. Plus, the cytokines which are important for NK cells' activity, including IL-12, IL-15 and IL-21 were not detected. Besides, the serum level of soluble CD25 which is negatively correlated with percentages of NK cells was significantly elevated
[17]
Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection
PB
12 HC, 7 moderate P, 27 severe P, 6 recovered P
Wide changes in NK cells during COVID-19. NK cells returned to normal range after recovery
[14]
Unique immunological profile in patients with COVID-19
PB, BALF
32 P, 25 HC
Absolute NK cell count was significantly lower in COVID-19 patients compared with controls, whereas the NK cell frequency did not differ between the two groups
[18]
NK cell activation related to clinical outcome of COVID-19
PB
27 P, 17 HC
Adaptive NK cell expansion was observed
[16]
Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
BALF
13 P, 3 HC
The number of NK cells increased in BALF of COVID-19 patients
[15]
Heightened innate immune responses in the respiratory tract of COVID-19 patients BALF 8 P, 146 CAP, 20 HC The number of NK cells decreased in BALF of COVID-19 patients [20]
Phenotype and function
SARS-CoV-2 Spike 1 protein controls NK cell activation via the HLA-E/NKG2A pathway
PB
4 HC
Intracellular expression of SARS-CoV-2 Spike protein 1 causes lower NK cell degranulation via the HLA-E/NKG2A pathway
[21]
An inflammatory profile correlates with decreased frequency of cytotoxic cells in coronavirus disease 2019
PB
48 P, 20 HC
The number of NK cells expressing perforin decreased in patients in ICU
[22]
Transplantation of ACE2 mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia
PB
10 (7 MSCs transplant, 3 Placebo)
CXCR3 NK cells were increased significantly in comparison to HC which results in a cytokine storm. In contrast, in patients who underwent MSC transplantation, the overreacted NK cells disappeared
[23]
Identification of druggable inhibitory immune checkpoints on NK cells in COVID-19
PB
82 (10 HC, 10 paucisymptomatic COVID-19, 34 pneumonia, 28 ARDS due to COVID-19)
The expression level of NKG2C remained intact
[24]
Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19
DNA from respiratory swabs
361 P
Patients with NKG2C/HLA-E variants are more susceptible to development of severe SARS-CoV-2
[25]
Unique immunological profile in patients with COVID-19
PB, BALF
32 P, 25 HC
The expression of NKG2D and DNAM-1, known as activating receptors of NK cells, was reduced in COVID-19 patients compared with HC
[18]
A single-cell atlas of the peripheral immune response in patients with severe COVID-19 PB 7 P, 6 HC Most COVID-19 patients’ NK cells expressed exhaustion markers, including LAG3, TIM-3, PDCD1 and HAVCR2 [26]
Education
NK cell activation related to clinical outcome of COVID-19
PB
27 P, 17 HC
No changes were observed in KIR receptors’ expression on NK cells
[16]
Identification of druggable inhibitory immune checkpoints on NK cells in COVID-19 PB 82 (10 HC, 10 paucisymptomatic COVID-19, 34 pneumonia, 28 ARDS due to COVID-19) Robust expression of KIR2DL1/S1 receptors on NK cells’ surface. Besides, No changes were observed in other KIR receptors [24]

ARDS: Acute respiratory distress syndrome; BALF: Bronchoalveolar lavage fluid; CAP: Community acquired pneumonia patients; HC: Healthy control; ICU: Intensive care unit; NK: Natural killer cell; P: Patient; PB: Peripheral blood.