The most common symptomatic primary immunodeficiency, common variable immunodeficiency (CVID), is a genetically heterogeneous group of rare diseases associated with significantly increased risk of mortality and marked by hypogammaglobulinemia, a failure to produce antibodies in response to antigens, and repeated bacterial infections. It affects 1 in 30 000 people. Patients have poor response to antibiotics, illnesses undeterred by vaccinations, and recurrent complicating conditions such as bronchitis, sinusitis, bronchiectasis, bacterial pneumonia, otitis media, and pulmonary damage. Although up to one-third of patients will present in the first decade of life, diagnosis typically occurs in the second to fourth decade. There is no sex predilection overall, although males more commonly present in childhood and women present as adults.

Patients most commonly present with infectious complications, usually with sinus or respiratory infections, as those with CVID are susceptible to infections caused by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae), respiratory viruses, and atypical bacteria. Recurrent infections over time progress to structural consequences such as chronic lung disease. In one large systematic review of CVID cases, other infectious complications included bacteremia (8%), mastoiditis (8%), meningitis (6%), and osteomyelitis (4%) and noninfectious complications included inflammatory bowel disease (11%), autoimmune cytopenias (10%), and idiopathic thrombocytopenia (6%).

Lymphadenopathy, splenomegaly, and cancers such as lymphoma and gastric cancer may occur.