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

Abstract

BackgroundThe contemporaneous presence of immune-defects and heart diseases in patients with 22q11.2 deletion syndrome might represent risk factors for severe COVID-19.ObjectiveTo analyze SARS-CoV-2 outcome in 22q11.2DS patients and immunogenicity of different doses of mRNA SARS-CoV-2 vaccine.MethodsLongitudinal observational study on SARS-Cov-2 outcome in 60 adults with 22q11.2DS (March 2020-June 2022). Anti-Spike, and anti-receptor binding domain antibody responses, generation of Spike-specific memory B-cells and Spike-specific T-cells at different time points before and after the mRNA BNT162b2 vaccination were evaluated in sixteen 22q11.2DS patients.ResultsWe 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, six after receiving two doses of vaccine and twelve after the booster dose. SARS-CoV-2- infection had a mild course, except 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, COVID-19 did not impact cardiological conditions. The BNT162b2 vaccine induced S1-IgG responses, low serum S1-IgA, and slightly impaired specific memory B-response. Specific T-cell responses observed were related to lymphocytes and CD4+ T cell counts.ConclusionSARS-CoV-2 infection had a mild course in most patients with 22q11.2DS, even in patients with major cardiovascular diseases. Immunization induced Spike-specific IgG responses and generated specific memory B and T cells. The weaker memory responses in patients with lymphopenia suggested the need for additional doses.