Background SARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEI); however, little is known about immunogenicity and safety in these patients. Objectives To evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse event (AE) in a cohort of patients with IEI. Methods Plasma was collected from twenty-two healthcare worker (HCW) controls, 81 IEI patients and 2 thymoma pre-immunization, 1 to 6 days prior to the second dose of mRNA vaccine and at a median of 30 days after completion of the immunization schedule with either mRNA vaccine or a single dose of Johnson & Johnson’s Janssen vaccine. Anti-Spike (S) and anti-Nucleocapsid (N) antibody titers were measured using a luciferase immunoprecipitation systems (LIPS) method. T and B cell counts and use of immunosuppressive drugs were extracted from medical records. Vaccine-associated AE were collected after each dose. Results Positive anti-S antibodies were detected in 27/46 (58.7%) of the patients after one dose of mRNA vaccine and in 63 of 74 (85.1%) fully immunized patients. A lower rate of seroconversion (7/11, 63.6%) was observed in patients APECED. Previous use of rituximab and baseline counts of <1,000 CD3 + T cells/μL and <100 CD19 + B cells/μL were associated with lower anti-S IgG levels. No significant adverse events were reported. Conclusion Vaccinating IEI patients is safe, but immunogenicity is impacted by certain therapies and gene defects. These data may guide counseling IEI patients on prevention of SARS-CoV-2 infection and need for subsequent boosts.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute (NCI) cross-sectional chronic Graft-versus-Host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures including the 2005 NIH Consensus Project cGVHD severity score. The purpose of this study is to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in order to standardize clinician evaluation and staging of cGVHD. 125 of 189 patients met criteria for severe cGVHD on the NIH global score and 62 had moderate disease, with a median of 4 (range 1–8) involved organs. Clinician average NIH organ score and the corresponding organ scores performed by subspecialists were highly correlated (r=0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures including Lee Scale, SF-36 Physical Component Scale (PCS), 2 minutes walk, grip strength, range of motion and Human Activity Profile (HAP). Joints/fascia, skin, and lung involvement impacted function and quality of life most significantly and showed highest number of correlations with outcome measures. The final Cox model showing factors jointly predictive for survival contained the time from cGVHD diagnosis (>49 vs. ≤49 months, HR=0.23; p=0.0011), absolute eosinophil count of (0–0.5 vs. >0.5 cells/µL, HR=3.95; p=0.0006) at the time of NIH evaluation, and NIH lung score (3 vs. 0–2, HR=11.02; p <0.0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. Strong association with subspecialist evaluation suggests that NIH organs and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex sub-specialist exams. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors.