Common Variable Immunodeficiency Associated with a De Novo Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine.

BACKGROUND AND AIMS

Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARS-CoV-2 vaccine.

METHODS

We performed a next-generation sequencing analysis, a CMIA, and an ELISA to analyze the humoral and cellular response to the SARS-CoV-2 vaccine, respectively. We also employed flow cytometry and immunoturbidimetry to assess the patient's global immune status.

RESULTS

We found a low humoral but positive cellular response to the SARS-CoV-2 vaccine. NGS screening revealed a transition from guanine to adenine at position c.485 of the gene in heterozygosity, giving rise to the R162Q variant, which was not present in his parents.

CONCLUSIONS

The R162Q variant of the gene has been associated with CVID type 13, but always with an autosomal dominant inheritance with high penetrance. Therefore, we present for the first time a case of CVID associated with a de novo heterozygous R162Q variant in the gene in a patient with a low humoral immune response to the complete COVID-19 vaccination program.