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Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort
  1. Sakir Ahmed1,
  2. Pankti Mehta2,
  3. Aby Paul3,
  4. S Anu3,
  5. Somy Cherian3,
  6. Veena Shenoy4,
  7. Kaveri K Nalianda3,
  8. Sanjana Joseph3,
  9. Anagha Poulose3,
  10. Padmanabha Shenoy5
  1. 1 Clinical Immunology & Rheumatology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
  2. 2 Clinical Immunology and Rheumatology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
  3. 3 Centre for Arthritis and Rheumatism Excellence (CARE), Sree Sudheendra Medical Mission, Kochi, Kerala, India
  4. 4 Department of Transfusion Medicine, Amrita Institute of Medical Sciences, Cochin, Kerala, India
  5. 5 Centre for Arthritis and Rheumatism Excellence (CARE), Kochi, Kerala, India
  1. Correspondence to Dr Padmanabha Shenoy, Centre for Arthritis and Rheumatism Excellence (CARE), Cochin, Kerala, India; drdpshenoy{at}gmail.com

Abstract

Introduction To assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections.

Methods Patients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4–6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8–212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies.

Results We studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.

Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection.

Conclusion Breakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

  • Covid-19
  • vaccination
  • arthritis
  • antirheumatic agents

Data availability statement

Data are available on reasonable request. Data will be available from the corresponding author on reasonable request.

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Data availability statement

Data are available on reasonable request. Data will be available from the corresponding author on reasonable request.

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Footnotes

  • Handling editor Josef S Smolen

  • Twitter @sakir_rheum, @PanktiMehta24, @drdpshenoy

  • Contributors PS, VS and SAh designed the study . Patient enrolment and data collection was done by PS,AP, SC, SAn, SJ, VS and KKN. Manuscript was draft by SAn and PM. PS accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Competing interests SA has received honorarium as speaker from Pfizer, DrReddy’s, Cipla and Novartis (unrelated to the current work). The other authors declare no conflicts of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.