Abstract
SARS-CoV-2 is the causative agent for the global COVID-19 pandemic; however, the interaction between virus and host is not well characterized. Natural killer cells play a key role in the early phase of the antiviral response, and their primary functions are dependent on signaling through the killer cell immunoglobulin-like receptor (KIR). This study measured the association between KIR/HLA class I ligand pairings and the occurrence and development of COVID-19. DNA of blood samples from 257 COVID-19 patients were extracted and used to detect KIR and HLA-C gene frequencies using single strain sequence-specific primer (SSP) PCR. The frequency of these genes was compared among 158 individuals with mild COVID-19, 99 with severe disease, and 98 healthy controls. The frequencies of KIR2DL2 (P=0.04, OR=1.707), KIR2DS3 (P=0.047, OR=1.679), HLA-C1C1 (P<0.001, OR=3.074) and the KIR2DL2/HLA-C1C1 pairing (P=0.038, OR=2.126) were significantly higher in the COVID-19 patients than the healthy controls. At the same time, the frequency of KIR2DL3+KIR2DL2-/HLA-C1+Others+ was lower in COVID-19 patients than in healthy individuals (P=0.004, OR=0.477). These results suggest that the protective effect of KIR2DL3 against SARS-CoV-2 infection is related to the absence of the KIR2DL2 gene. This study found no correlation between the frequencies of these genes and COVID-19 pathogenesis. Global statistical analysis revealed that the incidence of COVID-19 infection was higher in geographic regions with a high frequency of KIR2DL2. Together these results suggest that the KIR2DL2/HLA-C1C1 gene pairing may be a risk factor for SARS-CoV-2 infection.
Keywords: COVID-19; HLA; KIR; NK cells; SARS-CoV-2.
【저자키워드】 COVID-19, NK cells, SARS-CoV-2., HLA, KIR, 【초록키워드】 SARS-CoV-2, SARS-COV-2 infection, Infection, NK cells, risk factor, virus, DNA, Region, PCR, COVID-19 pathogenesis, COVID-19 infection, Mild, Natural killer cells, receptor, function, COVID-19 patients, protective effect, association, Signaling, natural killer cell, antiviral response, Ligand, Interaction, Frequency, severe disease, statistical analysis, COVID-19 patient, causative agent, frequencies, Blood samples, healthy individuals, individual, early phase, blood sample, Killer cell, healthy controls, no correlation, HLA-C, primer, Host, controls, Cell, KIR2DL2, KIR2DL3, KIR2DS3, Occurrence, detect, characterized, absence, dependent on, significantly higher, in healthy individual, incidence of COVID-19, the healthy, 【제목키워드】 SARS-CoV-2, Increased, Pairing,