Dataset of single nucleotide polymorphisms of immune-associated genes in patients with SARS-CoV-2 infection

Abstract

The SARS-CoV-2 pandemic has affected nations globally leading to illness, death, and economic downturn. Why disease severity, ranging from no symptoms to the requirement for extracorporeal membrane oxygenation, varies between patients is still incompletely understood. Consequently, we aimed at understanding the impact of genetic factors on disease severity in infection with SARS-CoV-2. Here, we provide data on demographics, ABO blood group, human leukocyte antigen (HLA) type, as well as next-generation sequencing data of genes in the natural killer cell receptor family, the renin-angiotensin-aldosterone and kallikrein-kinin systems and others in 159 patients with SARS-CoV-2 infection, stratified into seven categories of disease severity. We provide single-nucleotide polymorphism (SNP) data on the patients and a protein structural analysis as a case study on a SNP in the SIGLEC7 gene, which was significantly associated with the clinical score. Our data represent a resource for correlation analyses involving genetic factors and disease severity and may help predict outcomes in infections with future SARS-CoV-2 variants and aid vaccine adaptation.

Fig 1. Experimental workflow.

Fig 2. Genes targeted in the next-generation sequencing panel and list of rare variants.

Fig 3. Descriptive statistics.

(A) The number of patients within age groups. (B) The number of patients versus clinical score. (C) The number of patients versus ABO blood type. (D) The number of patients versus HLA-A type. (E) The number of patients versus HLA-B type. (F) The number of patients versus HLA-C type. (G) The number of patients versus HLA-DRB1 type. (H) The number of patients versus HLA-DQB1 type. (I) The number of patients versus HLA-DPB1 type. (J) Mean clinical score versus ABO blood type. (K) Mean clinical score versus HLA-A type. (L) Mean clinical score versus HLA-B type. (M) Mean clinical score versus HLA-C type. (N) Mean clinical score versus HLA-DRB1 type. (O) Mean clinical score versus HLA-DQB1 type. (P) Mean clinical score versus HLA-DPB1 type. (J-O) The black line shows the overall mean of the clinical score of 2.81. The black bullets show the mean clinical score for patient groups. Violin plots superimposed by box plots indicate the densities of clinical scores. We found no statistical significance for any of the subgroups in J-P regarding the deviation of their mean clinical score from the overall mean clinical score of 2.81, i.e. Mann-Whitney U tests gave significance values larger than 5%.

Fig 4. Significance of age and gender.

(A) Jitter plot of clinical score versus age. (B) Mean clinical score versus age group. (C) Mean clinical scores of female versus male patients of all ages. (B, C) The black line shows the overall mean of the clinical score of 2.81. The black bullets show the mean clinical score for patient groups. Violin plots superimposed by box plots indicate the densities of clinical scores. (D) Receiver operating characteristics (ROC) of a random forest prediction of hospitalization, i.e., clinical score 4–7, based on age and gender.

Fig 5. Single-nucleotide polymorphisms in patient cohort.

A) Number of SNPs per patient. An average of approximately 220 SNPs per patient was detected. B) Comparison of the number of SNPs with zygosity. C) Comparison of the occurrence of missense SNPs in the low versus high clinical score. D) The whole AlphaFold-predicted structure, AF-Q9Y286-F1, of the nonsynonymous SNP, rs993496436, encoding the protein sialic acid-binding Ig-like lectin 7 (SIGLEC7) in humans (Q9Y286). The mutated serine is illustrated in a stick-and-ball representation. It is located within the light blue-colored area in ribbon representation, exhibiting a confidence score of 70 to 90, whereby 100 is the best score. The figure was generated using AlphaFold software. E) Magnification of the mutated serine illustrated in a stick-and-ball representation as in D). The mutated serine is located within a light blue-colored range, standing for a confidence score of 70 to 90.