Papel de las células Natural Killer en la susceptibilidad y el pronóstico de la COVID-19

Abstract

The immunological mechanisms involved in the etiopathogenesis and prognostic associated factors of coronavirus disease 2019 (COVID-19) remain to be elucidated. In this study, we investigated the role of killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen class-I (HLA-I) interactions in the susceptibility and severity of COVID-19; as well as we analyze the prognostic value of demographic, analytical and clinical factors associated with the severity of COVID-19 METHODOLOGY This was a cross-sectional, retrospective study with analytical components in which 201 patients with SARS-CoV2 infection were included, of whom 100 had presented with mild and/or moderate symptomatology (1 to 4) and the rest severe (5 or 6) according to the modified WHO classification. In addition, they were compared with 610 healthy controls. We performed KIR and HLA-I genotyping and natural killer cell receptor immunophenotyping. A descriptive analysis was performed followed by binary logistic regression of the variables associated with severity. The SPSS v22 statistical program and the free software "r" were used. It was considered significant if the "p" was less than 0.05. RESULTS NK cells with a distinctive immunophenotype, suggesting recent activation (KIR2DS4low CD16low CD226low CD56high TIGIThigh NKG2Ahigh), were expanded in patients with severe COVID-19. This was associated with a higher frequency of the A- telomeric functional activating receptor KIR2DS4 in severe versus mild and/or moderate patients and controls (83.7%, 55.7% and 36.2%, p <7.7 × 10 -9). In patients with mild and/or moderate infection, HLA-B*15:01 was associated with higher frequencies of B-telomeric activating receptor KIR3DS1 compared with patients with other HLA-B*15 subtypes and uninfected controls (90.9%, 42.9% and 47.3%; p <.002; Pc = 0.022). This strongly suggests that HLA-B*15:01 by specific presentation of peptides from the SARS-CoV2, could form a neoligand that interacts with KIR3DS1. Likewise, a putative neoligand for KIR2DS4 could arise from other HLA-I molecules presenting SARS-CoV2 peptide expressed on infected and/or activated antigen-presenting lung cells. CONCLUSIONS Our results confirm the existence of demographic, clinical and analytical factors that have prognostic value for severe COVID-19, and support a crucial role of NK cells in the clinical variability of COVID-19 with specific KIR/ligand interactions associated with disease severity. Specifically, KIR2DS4 receptor was statistically significantly associated with a more severe clinical course of disease following SARS-CoV2 infection.