Health-Related Quality of Life Reveals Distinct Fatigue and Functional Burden in Inflammatory Common Variable Immunodeficiency

Rationale Common variable immunodeficiency (CVID) is a chronic, multisystem immune disorder associated with substantial symptom burden beyond infections, particularly among individuals with noninfectious inflammatory complications (CVIDc). Fatigue and impaired functioning are frequently reported by patients but remain under-characterized using standardized, validated patient-reported outcome (PRO) instruments in major cohorts. Systematic assessment of health-related quality of life (HRQOL) using population-referenced tools may clarify patient-perceived disease impact across CVID phenotypes and inform patient-centered outcome assessment. Methods We conducted a cross-sectional observational study of CVID patients followed at Mount Sinai Hospital. Participants completed the PROMIS-29 Profile and the FACIT-Fatigue scale. PROMIS-29 domain scores were reported as T-scores standardized to the U.S. general population (mean 50, SD 10), with domain-specific directionality applied. FACIT-Fatigue scores were analyzed using standard scoring conventions, with higher scores indicating less fatigue. Participants were clinically categorized as uncomplicated CVID (CVIDu) or CVID with noninfectious inflammatory complications (CVIDc). Results Among 40 participants to date (CVIDu n = 15; CVIDc n = 25), fatigue burden and functional status differed by clinical phenotype. CVIDu participants reported better fatigue status on FACIT-Fatigue than CVIDc (median 46 vs. 36; mean 42.5 vs. 35.2), indicating greater fatigue in CVIDc. PROMIS-29 demonstrated a concordant pattern: domains reflecting symptom burden (fatigue, anxiety, depression, pain interference, and sleep disturbance) were directionally worse in CVIDc, while domains reflecting functioning (physical function and social participation) were lower, indicating reduced everyday functioning. Although not powered for formal statistical inference to date, the consistency of effect direction across PROMIS and FACIT instruments supports a coherent HRQOL profile characterized by greater fatigue and functional impairment in CVIDc. Exploratory analyses showed no consistent overall correlations between PROs and baseline immunologic parameters, including lymphocyte profiles and immunoglobulin levels. Conclusion CVID patients with inflammatory complications exhibit a consistent pattern of increased fatigue and impaired functioning across complementary PRO measures. These findings underscore HRQOL, and fatigue in particular, as a meaningful dimension of disease burden in CVIDc that is not fully captured by traditional clinical or immunologic assessments, supporting broader incorporation of standardized PROs into CVID research and outcome evaluation.