Pos0551 sars-cov-2 breakthrough infection in covid-19-vaccinated adolescents and young adults with childhood-onset rheumatic diseases

Background Although robust humoral immune response after 2-dosed COVID-19 mRNA vaccination was demonstrated in adolescents and young adults (AYAs) with childhood-onset rheumatic diseases (cRDs) [1] , data on prevalence and risk factors of SARS-CoV-2 breakthrough infection are limited. Objectives To describe the clinical characteristics and risk factors for SARS-CoV-2 breakthrough infection in vaccinated AYAs with cRD from our prospective and ongoing cRDs COVID-19 vaccination cohort. Methods Patients were recruited from March 2021 – December 2022 at KK Women’s and Children’s Hospital, Singapore. Breakthrough infections were defined as symptomatic infections occurring ≥14 days after the second dose in a two-dose series [2] . 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 and calibrated against the World Health Organisation International Standard for SARS-CoV-2 antibodies (WHO-nAb). Results 170 fully COVID-19 mRNA vaccinated patients (71% Chinese, 47% male) were included, Table 1. 141 patients received 3 rd vaccine, 6 months after the full series. 51% had breakthrough infection at a median of 5.6 (IQR 4.0-6.8, n=22) and 3.7 (IQR 1.3-5.4, n=55) months after 2 nd or 3 rd vaccines, respectively, with mainly mild symptoms (5% admission). The median WHO-nAb was significantly lower in those with breakthrough infection (987.3 IU/ml, IQR 361.0 - 2083.4 vs 1892.1 IU/ml, IQR 1052.5 - 2657.7, p<0.001). Older patients had decreased risk of breakthrough SARS-CoV-2 infection (OR 0.83, 95% CI 0.739-0.936, p=0.002). A WHO-nAb titre of < 1000 IU/ml increased the risk of breakthrough SARS-CoV-2 infection (OR 4.16, 95% CI 1.964-8.794, p<0.001). Significantly more patients with infection were taking anti-TNF. Withholding methotrexate or mycophenolate mofetil did not impact the breakthrough infection risk. Conclusion Despite a robust humoral immune response to COVID-19 mRNA 2-dosed vaccination, one-half of the AYAs with cRDs had breakthrough infections, albeit mild disease. Younger patients and WHO-nAb < 1000 IU/ml increased the risk of infection. Additional vaccine is needed sooner than 6 months after the 2 nd dose to prevent infection. Longitudinal data are being collected to determine the vaccine booster interval in our cohort. References [1]Yeo JG, Chia WN, Teh KL, Book YX, Hoh SF, Gao X, Das L, Zhang J, Sutamam N, Lim AJM, Poh SL, Tay SH, Nay Yaung K, Ong XM, Hazirah SN, Chua CJH, Leong JY, Wang LF, Albani S, Arkachaisri T. Robust neutralising antibody response to SARS-CoV-2 mRNA vaccination in adolescents and young adults with childhood onset rheumatic diseases. Rheumatology (Oxford). 2022 Feb 23:keac105. doi: 10.1093/rheumatology/keac105 [2]CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 Vaccine Breakthrough Infections Reported to CDC - United States, January 1-April 30, 2021. MMWR Morb Mortal Wkly Rep 2021;70:792–3. Table 1. Clinical characteristics of vaccinated AYA with cRD Clinical characteristics Total No infection, n=83 Infection, n=87 p Male 80 (47.1) 40 (48.2) 40 (46.0) 0.772 Age (yrs) 16.7 (14.7-19.5) 17.6 (15.1-20.0) 16.3 (14.1-19.2) 0.022 Diagnosis 0.742 Juvenile Idiopathic Arthritis 98 (57.6) 47 (56.6) 51 (58.6) Systemic Lupus Erythematosus 30 (17.6) 14 (16.9) 16 (18.4) Other Connective tissue diseases 21 (12.4) 13 (15.6) 8 (9.1) Others 21 (12.4) 9 (10.8) 12 (13.8) Medication Prednisolone 32 (18.8) 14 (16.9) 18 (20.7) 0.524 Anti-TNF 57 (33.5) 21 (25.3) 36 (41.1) 0.026 Hydroxychloroquine 43 (25.3) 24 (28.9) 19 (21.8) 0.289 Azathioprine 6 (3.5) 5 (6.0) 1 (1.1) 0.111 Mycophenolate mofetil (MMF) 22 (12.9) 13 (15.7) 9 (10.3) 0.302 Methotrexate (MTX) 42 (24.7) 18 (21.7) 24 (27.6) 0.373 Holding MTX 34 (81.0) 14 (77.8) 20 (83.3) 0.650 Holding MMF 7 (41.2) 4 (36.4) 3 (50.0) 0.644 Patients with WHO-nAb* titer < 1000 IU/ml (before infection or after vaccination) 54 (36.0) 20 (24.1) 34 (50.7) 0.001 *WHO-nAb: WHO International standardized neutralizing antibodies Acknowledgements: NIL. Disclosure of Interests None Declared.