COVID-19 Severity, Cardiological Outcome, and Immunogenicity of mRNA Vaccine on Adult Patients With 22q11.2 DS

BACKGROUND: The contemporaneous presence of immune defects and heart diseases in patients with 22q11.2 deletion syndrome (22q11.3DS) might represent risk factors for severe coronavirus 2019 disease (COVID-19).OBJECTIVE: To analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcome in 22q11.2DS patients and immunogenicity of different doses of mRNA SARS-CoV-2 vaccine. METHODS: Longitudinal observational study on SARS-CoV-2 outcome in 60 adults with 22q11.2DS (March 2020-June 2022). Anti-Spike, and anti-receptor binding domain (RBD) antibody responses, generation of Spike-specific memory B cells (MBCs) and Spike-specific T cells at different time points before and after the mRNA BNT162b2 vaccination were evaluated in 16 22q11.2DS patients.RESULTS: We recorded a 95% rate of vaccination, with almost all patients being immunized with the booster dose. Twenty-one patients had SARS-CoV-2 infection. Three patients were infected before vaccine availability, 6 after receiving 2 doses of vaccine, and 12 after one booster dose. The SARS-CoV-2-infection had a mild course, except in one unvaccinated patient with several comorbidities who died from acute respiratory distress syndrome (fatality rate 5%). Infected patients had more frequently moderate/severe intellectual disability, lymphopenia, and lower CD4+ count. Despite major congenital heart diseases, COVID19 did not impact cardiological conditions. The BNT162b2 vaccine induced S1-immunoglobulin G (IgG) responses, low serum S1-IgA, and slightly impaired specific MBCs response. Specific T-cell responses observed were related to lymphocytes and CD4+ T cell counts.CONCLUSIONS: The SARS-CoV-2 infection had a mild course in most patients with 22q11.2DS, even in patients with majorcardiovascular diseases. Immunization induced Spike-specific IgG responses and generated specific MBCs and memory T cells. The weaker memory responses in patients with lymphopenia suggested the need for additional doses. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/). (J Allergy Clin Immunol Pract 2023;11:292-305)

Automated summary

This study analyzed the relationship between immune defects and heart diseases in patients with 22q11.2 deletion syndrome (22q11.3DS) and the outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study found that most patients with 22q11.2DS had a mild course of SARS-CoV-2 infection, and vaccination induced specific antibody and memory cell responses.