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

Rheumatology (Oxford). 2023 Sep 1;62(9):3101-3109. doi: 10.1093/rheumatology/kead031.

Abstract

Objectives: To evaluate the humoral immunogenicity for 6 months after the two-dose coronavirus disease 2019 (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 and 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™ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralization antibody (nAb) assay. An inhibition signal of ≥30% defined the seroconversion threshold and the readings were calibrated against the World Health Organization International Standard for SARS-CoV-2 antibodies.

Results. one hundred and sixty-nine: AYAs with cRDs were recruited [median age 16.8 years (interquartile range, IQR 14.7-19.5), 52% female, 72% Chinese]. JIA (58%) and SLE (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 [odds ratio (OR) 10.1, 95% CI 1.8-58.4, P = 0.010] and treatment with anti-TNF-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 MTX or MMF 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.

Keywords: COVID vaccine; COVID-19 infection; SARS-CoV-2; childhood-onset rheumatic diseases; vaccine effectiveness.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / epidemiology
  • COVID-19* / prevention & control
  • Child
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Rheumatic Diseases* / drug therapy
  • SARS-CoV-2
  • Tumor Necrosis Factor Inhibitors
  • Young Adult

Substances

  • COVID-19 Vaccines
  • Tumor Necrosis Factor Inhibitors
  • Antibodies, Viral

Supplementary concepts

  • COVID-19 breakthrough infections