**2. Materials and Methods**

#### *2.1. Subjects and Study Design*

The family (2 parents and the proband) was recruited at the Clinical Immunological Department of the University Hospital Virgen de las Nieves, Granada, Spain, as part of a continuous and systematic program of phenotyping and genotyping focused on CVID. The patient was diagnosed with CVID at the age of 25 due to recurrent episodes of bronchiectasis and respiratory infections. Since then, he has been under treatment with intravenous immunoglobulins with a good response and is currently clinically stable. His phenotype was evaluated with blood tests such as cytometry, immunoturbidimetry, chemiluminescence microparticle immunoassay (CMIA), and enzyme-linked immunosorbent assay (ELISA), as well as genetic studies of the patient and, subsequently, his parents.

The timeline of the study design is represented in Figure 1. All family members provided their written informed consent. The study was approved by the ethics committee, via the Portal de Ética de la Investigación Biomédica de Andalucía, Junta de Andalucía (Code: 0297-N-21).

**Figure 1.** Study design. Timeline of the experimental plan and the schedule of the SARS-CoV-2 vaccine doses. CVID: common variable immunodeficiency; NSG: next-generation sequencing; IVIg: intravenous immunoglobulin treatment; Igs: immunoglobulins.
