Antibody Responses to the SARS-CoV-2 Vaccine in Individuals With Inborn Errors of Immunity

ABSTRACT

PURPOSE OF THE STUDY To evaluate the impact of genetic diagnosis and treatment on antibody response to coronavirus disease 2019 (COVID-19) vaccine and related adverse effects in patients with inborn errors of immunity (IEI). STUDY POPULATION Eighty-one patients with IEI (ages 13–71), 2 adults with thymoma and a control group consisting of 22 health care workers (HCWs) without histories of COVID-19 infection. METHODS: This was a longitudinal study of SARS-CoV-2 specific antispike (anti-S) and antinucleocapsid (anti-N) antibody levels in study subjects as compared with the control group. All subjects received SARS-CoV-2 immunizations between December 2020 and May 2021. Preimmunization anti-S and anti-N IgG levels were obtained in all the HCWs and 32 of 83 patients. For the study group, information on diagnosis, demographic data, history of COVID infection, type of vaccine received, interval between vaccine schedule completion (2 doses of messenger RNA [mRNA] vaccine or 1 dose of adenovirus vector vaccine) and sample collection, immunoglobulin replacement therapy, and use of immunomodulatory or immunosuppressive drugs were collected. RESULTS: Serology was obtained after completion of the recommended vaccine schedules for all the HCWs and 74 of 83 patients with immunodeficiency. Nine with IEI received just 1 dose of an mRNA vaccine and has serology obtained. All HCWs developed anti-S IgG after the first dose of vaccine with a broad range of response and 21 of 22 (95%, 95% confidence interval = 81.5% to 100%) had high levels after the second dose. The 1 exception was a HCW who 6 months earlier had received steroids and rituximab (a B-cell depleting monoclonal antibody) for antineutrophil cytoplasmic antibodies–positive granulomatous vasculitis. Of the immune deficient patients, 27 of 46 (58.7%) had positive anti-S IgG after 1 dose and 63 of 74 (85.4%, 95% confidence interval = 74.5% to 92%) after 2 doses of mRNA vaccines, a rate comparable to the HCWs. After 1 dose, the levels of anti-S IgG between groups approached but did not quite reach statistical significance (P = .06). In contrast, after 2 doses patients with IEI had lower levels than the HCWs (geometric mean = 611 938 light units vs 2 403 642 LU;P = .004). Some subgroups of patients IEI were less likely to have robust anti-S IgG response to immunization. Patients on rituximab, those with CD3+ (T lymphocyte) counts <1000/mL, and CD19+ (B lymphocyte) counts <100/mL had lower responses than those who did not meet those criteria. Most patients on immunoglobulin replacement therapy developed protective anti-S IgG levels after immunization. Adverse events of injection site redness, pain, and swelling and systemic symptoms were reported more commonly in patients with IEI than HCWs and more often after the second dose (local reactions 66.7% vs 27.3%;systemic reactions 52.9 vs 36.4% after the second dose). None of the systemic reactions were severe. CONCLUSIONS: COVID-19 immunization is safe and effective in patients with IEI. Some subsets of patients with IEI may not develop anti-S IgG levels after immunization.