Association study between killer immunoglobulin-like receptor polymorphisms and susceptibility to COVID-19 disease: a systematic review and meta-analysis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a known virus that leads to a respiratory disease called coronavirus disease 19 (COVID-19). Natural killer (NK) cells, as members of innate immunity, possess crucial roles in restricting viral infections, including COVID-19. Their functions and development depend on receiving signals through various receptors, of which killer cell immunoglobulin-like receptors (KIRs) belong to the most effective ones. Different studies investigated the association between KIR gene content and susceptibility to COVID-19. Since previous studies have yielded contradictory results, we designed this meta-analysis study to draw comprehensive conclusions about COVID-19 risk and KIR gene association. According to PRISMA guidelines, a systematic search was performed in the electronic databases to find all studies investigating KIR gene contents in COVID-19 patients before March 2023. Any association between KIR genes and COVID-19 risk was determined by calculating pooled odds ratio (OR) and 95% confidence interval (CI). After applying the inclusion and exclusion criteria, 1673 COVID-19 patients and 1526 healthy controls from eight studies were included in this meta-analysis. As the main results, we observed a positive association between the 2DL3 (OR = 1.48, 95% CI = 1.17-1.88, P < 0.001) and susceptibility to COVID-19 and a negative association between the 2DP1 and the risk for COVID-19 (OR = 0.48, 95% CI = 0.23-0.99, P = 0.049). This meta-analysis demonstrated that KIR2DL3, as a member of iKIRs, might be associated with an increased risk of COVID-19 disease.