COVID-19 mRNA vaccine immunogenicity decay and breakthrough illness in adolescents and young adults with childhood-onset rheumatic diseases.

ABSTRACT

OBJECTIVES: To evaluate the humoral immunogenicity for 6 months after the two-dose COVID-19 mRNA vaccination in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs). METHODS: This monocentric observational study was conducted between August 2020 to March 2022. Humoral immunogenicity was assessed at 2-3 weeks after first vaccine dose and 1, 3, and 6 months after the second dose by the cPass™ SARS-CoV-2 Neutralisation Antibody (nAb) Assay. An inhibition signal of ≥ 30% defined seroconversion threshold and the readings calibrated against the World Health Organisation (WHO) International Standard for SARS-CoV-2 antibodies. RESULTS: 169 AYAs with cRDs were recruited (median age 16·8 years (IQR 14·7-19·5), 52% female, 72% Chinese). Juvenile Idiopathic Arthritis (JIA) (58%) and Systemic Lupus Erythematosus (18%) comprised the major diagnoses. After second vaccine dose, 99% seroconverted with a median nAb titre of 1779·8 IU/ml (IQR 882·8-2541·9), declining to 935·6 IU/ml (IQR 261·0-1514·9) and 683·2 IU/ml (IQR 163·5-1400·5) at the 3- and 6-month timepoints respectively. The diagnosis of JIA (OR 10·1, 95%CI 1·8-58·4, p= 0·010) and treatment with anti-Tumour Necrosis Factor-α (aTNF) (OR 10·1, 95%CI 1·5-70·0, p= 0·019) were independently associated with a > 50% drop of nAb titres at 6 months. Withholding methotrexate or mycophenolate mofetil did not affect the vaccine response or decay rate. The COVID-19 breakthrough infection was estimated at 18·2 cases/1000 patient-months with no clinical risk factors identified. CONCLUSION: Over half of AYAs with cRDs had a significant drop in SARS-CoV-2 nAb at 6-month despite an initial robust humoral response. JIA and aTNF usage are predictors of a faster decay rate.