ABSTRACT
BACKGROUND: Although widely reported to affect older adults more, coronavirus disease 2019 (COVID-19) also affects adolescents, especially those with co-morbidities, including heart diseases. The safety and efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines has been established in healthy adolescents, yet there are few data for humoral and cellular immunogenicity in adolescents with cardiac diseases. METHODS: We evaluated anti-spike antibodies, neutralizing activities, and interferon-gamma production prior to and after SARS-CoV-2 vaccination in adolescents with cardiac diseases and healthy controls. RESULTS: Five healthy adolescents and 26 patients with cardiac diseases, including congenital heart disease (CHD, n = 10), dilated cardiomyopathy (DCM, n = 4), idiopathic pulmonary arterial hypertension (IPAH, n = 4), and those post-heart transplantation (post-HTx, n = 8) were enrolled. No severe adverse events, including myocarditis and pericarditis, were noted, even in patients with severe heart failure. Febrile events were noted after 21 of 62 injections (34%). All the healthy adolescents and 21 of the 26 patients (81%) showed sufficient elevation of neutralizing antibodies after the second dose of vaccination. Neutralizing antibodies and cellular immunity were absent in four of the eight post-HTx patients and one with single ventricle CHD. There was no correlation between the anti-spike and neutralizing antibody titers and interferon-gamma levels. When comparing the clinical characteristics of the patients post-HTx who did or did not acquire antibodies, there was no significant difference in the immunosuppressant types and trough levels. CONCLUSIONS: SARS-CoV-2 mRNA vaccine has efficient immunogenicity for adolescents with CHD, IPAH, and DCM. Half of post-HTx patients could not acquire sufficient humoral immunity.
Subject(s)
COVID-19 , Heart Diseases , Viral Vaccines , Adolescent , Humans , Aged , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , Interferon-gamma , Antibodies, Viral , Viral Vaccines/adverse effects , Antibodies, Neutralizing , Vaccination , Heart Diseases/chemically inducedABSTRACT
Background Although widely reported to affect older adults more, coronavirus disease 2019 also affects adolescents especially with co‐morbidities, including heart diseases. The safety and efficacy of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) mRNA vaccines was established in healthy adolescents, yet there were few data for humoral and cellular immunogenicity in adolescents with cardiac diseases. Methods We evaluated anti‐spike antibodies, neutralizing activities, and interferon‐gamma production prior to and post SARS‐CoV‐2 vaccination in adolescents with cardiac diseases and healthy controls. Results Five healthy adolescents and 26 patients cardiac diseases including congenital heart disease (CHD, n=10), dilated cardiomyopathy (DCM, n=4), idiopathic pulmonary arterial hypertension (IPAH, n=4), and post‐heart transplantation (HTx, n=8) were enrolled. No severe adverse events including myocarditis and pericarditis were noted, even in patients with severe heart failure. Febrile events were noted in 21 of 62 injections (34%). All the healthy adolescents and 21 of the 26 patients (81%) showed sufficient elevation of neutralizing antibodies after the second dose of vaccination. Neutralizing antibodies and cellular immunity were absent in four of the eight post‐HTx patients and one with CHD of single ventricle. There was no correlation between the anti‐spike and neutralizing antibody titers and interferon‐gamma levels. When comparing the clinical characteristics of the patients post‐HTx who did or did not acquire antibodies, there were no significant differences in the immunosuppressant types and trough levels. Conclusion SARS‐CoV‐2 mRNA vaccine has efficient immunogenicity for adolescents with CHD, IPAH, and DCM. Half of post‐HTx patients could not acquire sufficient humoral immunity.
ABSTRACT
PURPOSE: Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported. METHODS: After completing at least six months of a baseline observational growth study, and 52 weeks in a double-blind, placebo-controlled study, participants were eligible to continue treatment in an open-label extension study, where all participants received vosoritide at a dose of 15.0 µg/kg/day. RESULTS: In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. CONCLUSION: Vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia treated daily for two years.