Outcomes in children with rheumatic diseases following COVID-19 vaccination and infection: data from a large two-center cohort study in Thailand

Introduction Vaccination against coronavirus disease 2019 (COVID-19) is effective in protecting patients from severe COVID-19 infection. Disease flare-up following immunization in children with rheumatic disorders may result in patient reluctance to receive the vaccine. Underlying rheumatic diseases or the use of immunosuppressive drugs may influence the outcomes of COVID-19 vaccination and infection. We aimed to describe outcomes in children with rheumatic diseases following COVID-19 immunization and infection. Methods This retrospective study was performed at two large academic centers in Thailand. During the COVID-19 pandemic, all patients were routinely queried about COVID-19-related conditions. We included patients with rheumatic diseases aged <18 years who received at least one dose of a COVID-19 vaccine or had a history of COVID-19 infection with more than 6 months of recorded follow-up after the last vaccine dose or COVID-19 illness. Demographic information and data on clinical symptoms, disease activity, treatment, outcomes, and COVID-19 vaccination and infection were collected. Results A total of 479 patients were included. Most (229; 47.81%) patients had juvenile idiopathic arthritis, followed by connective tissue diseases (189; 39.46%), vasculitis syndromes (42; 8.76%), and other rheumatic diseases (19; 3.97%). Approximately 90% of patients received at least one dose of COVID-19 vaccination, and half of the patients had COVID-19 infection. Among patients, 10.72% and 3.27% developed a flare after COVID-19 vaccination and COVID-19 illness, respectively. Flare severity after COVID immunization and infection was mainly mild to moderate. The predictor of flare after COVID-19 vaccination was the use of prednisolone ≥10 mg/day before vaccination (hazard ratio: 2.04, 95% confidence interval: 1.05–3.97, p = 0.037). Inactive disease before receiving the COVID-19 vaccination was a predictor of inactive status after a flare (hazard ratio: 2.95, 95% confidence interval: 1.04–8.40; p = 0.043). Overall, 3.36% and 1.61% of patients experienced a new onset of rheumatic disease after receiving the COVID-19 vaccine and after COVID-19 infection, respectively. Conclusion The COVID-19 vaccine is recommended for children with rheumatic disease, particularly those who are in stable condition. After COVID-19 vaccination, patients—especially those with active disease before vaccination or those receiving concurrent prednisolone doses of ≥10 mg/day—should be closely monitored.

[1]  P. Tharmaphornpilas,et al.  Real-World Effectiveness of COVID-19 Vaccines against Severe Outcomes during the Period of Omicron Predominance in Thailand: A Test-Negative Nationwide Case–Control Study , 2022, Vaccines.

[2]  L. Chew,et al.  Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING) , 2022, Journal of Autoimmunity.

[3]  X. Mariette,et al.  P61 SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry , 2022, Rheumatology Advances in Practice.

[4]  Monica Cabrera-Mora,et al.  Dysregulated naive B cells and de novo autoreactivity in severe COVID-19 , 2022, Nature.

[5]  Yang Liu,et al.  The Flare of Rheumatic Disease After SARS-CoV-2 Vaccination: A Review , 2022, Frontiers in Immunology.

[6]  X. Mariette,et al.  SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry , 2022, RMD Open.

[7]  S. Ozdel,et al.  Safety of COVID-19 vaccines and disease flares after vaccines in children with rheumatic disease , 2022, Postgraduate medicine.

[8]  H. Brüssow COVID‐19: Omicron – the latest, the least virulent, but probably not the last variant of concern of SARS‐CoV‐2 , 2022, Microbial biotechnology.

[9]  U. Uygunoğlu,et al.  Safety of SARS-CoV-2 vaccination in patients with Behcet’s syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine , 2022, Rheumatology International.

[10]  N. Wulffraat,et al.  Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases , 2022, Annals of the Rheumatic Diseases.

[11]  S. Albani,et al.  Robust neutralizing antibody response to SARS-CoV-2 mRNA vaccination in adolescents and young adults with childhood-onset rheumatic diseases , 2022, Rheumatology.

[12]  G. Shefer,et al.  Safety and immunogenicity of BNT162b2 mRNA COVID-19 vaccine in adolescents with rheumatic diseases treated with immunomodulatory medications , 2022, Rheumatology.

[13]  N. Apiwattanakul,et al.  Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus , 2022, PloS one.

[14]  R. Caporali,et al.  Low frequency of disease flare in patients with rheumatic musculoskeletal diseases who received SARS-CoV-2 mRNA vaccine , 2022, Arthritis Research & Therapy.

[15]  M. Yıldız,et al.  Early experience of COVID‐19 vaccine‐related adverse events among adolescents and young adults with rheumatic diseases: A single‐center study , 2022, International journal of rheumatic diseases.

[16]  G. Hernández-Molina,et al.  New Onset of Autoimmune Diseases Following COVID-19 Diagnosis , 2021, Cells.

[17]  R. Ionescu,et al.  COVID-19 Vaccine Does Not Increase the Risk of Disease Flare-Ups among Patients with Autoimmune and Immune-Mediated Diseases , 2021, Journal of personalized medicine.

[18]  Zhuoli Zhang,et al.  Safety and disease flare of autoimmune inflammatory rheumatic diseases: a large real-world survey on inactivated COVID-19 vaccines , 2021, Annals of the Rheumatic Diseases.

[19]  E. Zavala-Flores,et al.  Side effects and flares risk after SARS-CoV-2 vaccination in patients with systemic lupus erythematosus , 2021, Clinical Rheumatology.

[20]  M. Tsolia,et al.  Safety and tolerability of the COVID‐19 messenger RNA vaccine in adolescents with juvenile idiopathic arthritis treated with tumor necrosis factor inhibitors , 2021, Arthritis & rheumatology.

[21]  J. Haas,et al.  Infection with SARS-CoV-2 causes flares in patients with juvenile idiopathic arthritis in remission or inactive disease on medication , 2021, Pediatric Rheumatology.

[22]  Andrew T. Kroger,et al.  American College of Rheumatology Guidance for COVID‐19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 3 , 2021, Arthritis & rheumatology.

[23]  D. Segev,et al.  Disease Flare and Reactogenicity in Patients With Rheumatic and Musculoskeletal Diseases Following Two‐Dose SARS–CoV‐2 Messenger RNA Vaccination , 2021, Arthritis & rheumatology.

[24]  Mimi Y. Kim,et al.  Evaluation of Immune Response and Disease Status in Systemic Lupus Erythematosus Patients Following SARS–CoV‐2 Vaccination , 2021, Arthritis & rheumatology.

[25]  L. Arnaud,et al.  Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study , 2021, The Lancet Rheumatology.

[26]  K. Minden,et al.  Clinical manifestations and outcome of SARS-CoV-2 infections in children and adolescents with rheumatic musculoskeletal diseases: data from the National Paediatric Rheumatology Database in Germany , 2021, RMD Open.

[27]  L. Mandl,et al.  Systemic rheumatic disease flares after SARS-CoV-2 vaccination among rheumatology outpatients in New York City , 2021, Annals of the Rheumatic Diseases.

[28]  P. Shenoy,et al.  Safety of the ChAdOx1 nCoV-19 and the BBV152 vaccines in 724 patients with rheumatic diseases: a post-vaccination cross-sectional survey , 2021, Rheumatology International.

[29]  P. Sfikakis,et al.  Effective DNA damage response after acute but not chronic immune challenge: SARS-CoV-2 vaccine versus Systemic Lupus Erythematosus , 2021, Clinical Immunology.

[30]  Y. Braun-Moscovici,et al.  Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2 , 2021, Annals of the Rheumatic Diseases.

[31]  O. Zimba,et al.  COVID-19 and the clinical course of rheumatic manifestations , 2021, Clinical Rheumatology.

[32]  J. Teijaro,et al.  COVID-19 vaccines: modes of immune activation and future challenges , 2021, Nature Reviews Immunology.

[33]  B. Sözeri,et al.  SARS-CoV-2 infection in children with rheumatic disease: Experience of a tertiary referral center , 2021, Archives of rheumatology.

[34]  Q. Lu,et al.  COVID-19 and autoimmune diseases , 2020, Current opinion in rheumatology.

[35]  G. Church,et al.  Benchmarking evolutionary tinkering underlying human–viral molecular mimicry shows multiple host pulmonary–arterial peptides mimicked by SARS-CoV-2 , 2020, Cell death discovery.

[36]  A. Granito,et al.  COVID‐19 and Immunological Dysregulation: Can Autoantibodies be Useful? , 2020, Clinical and translational science.

[37]  Je-Min Choi,et al.  Bystander CD4+ T cells: crossroads between innate and adaptive immunity , 2020, Experimental & Molecular Medicine.

[38]  D. Kanduc From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry , 2020, Antibodies.

[39]  C. Gazzaruso,et al.  High prevalence of antinuclear antibodies and lupus anticoagulant in patients hospitalized for SARS-CoV2 pneumonia , 2020, Clinical Rheumatology.

[40]  Hanxiong Guan,et al.  Clinical features of rheumatic patients infected with COVID-19 in Wuhan, China , 2020, Annals of the Rheumatic Diseases.

[41]  R. Woods,et al.  Neutrophil extracellular traps in COVID-19. , 2020, JCI insight.

[42]  Can Hou,et al.  Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID‐19 , 2020, Clinical and translational science.

[43]  M. Dougados,et al.  2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases , 2019, Annals of the rheumatic diseases.

[44]  P. Albers,et al.  Experience of a tertiary referral center: Multivisceral approach and complications for post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in advanced germ cell tumors , 2018 .

[45]  D. Hébert,et al.  Childhood Takayasu arteritis: disease course and response to therapy , 2017, Arthritis Research & Therapy.

[46]  A. Ravelli,et al.  Clinical outcome measures in juvenile idiopathic arthritis , 2016, Pediatric Rheumatology.

[47]  S. Özen,et al.  Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS) , 2012, Annals of the rheumatic diseases.

[48]  N. Wulffraat,et al.  The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis , 2012, Annals of the rheumatic diseases.

[49]  Bin Huang,et al.  American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis , 2011, Arthritis care & research.

[50]  Y. Shoenfeld,et al.  Vaccines and Autoimmunity , 2013, International journal of immunopathology and pharmacology.

[51]  Y. Shoenfeld,et al.  Infections and autoimmunity--friends or foes? , 2009, Trends in immunology.

[52]  D. Gladman,et al.  Systemic lupus erythematosus disease activity index 2000. , 2002, The Journal of rheumatology.

[53]  R. Inman,et al.  Molecular mimicry and autoimmunity. , 1999, The New England journal of medicine.

[54]  OUP accepted manuscript , 2022, Rheumatology.

[55]  John D Lambris,et al.  Crossroads Between Innate and Adaptive Immunity V , 2015, Advances in Experimental Medicine and Biology.

[56]  J. R. Scotti,et al.  Available From , 1973 .

[57]  Robert C. Wolpert,et al.  A Review of the , 1985 .