Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort

Abstract

IntroductionTo 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.MethodsPatients 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.ResultsWe 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.ConclusionBreakthrough 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.

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune mediated inflammatory diseases

“…Although many IMID patients mount adequate serological responses to vaccination after two doses of an mRNA vaccine, a proportion of IMID patients show reduced responses compared to healthy controls (7-14), as confirmed in recent meta-analyses (15, 16). In particular, patients receiving glucocorticoids, methotrexate, mycophenolate, anti-TNF and B-cell depleting therapy may have attenuated serological responses to COVID-19 vaccines (7, 11, 13, 15, 17, 18). A small study of 23 IMID patients showed that patients on anti-TNF therapy have greater waning of humoral immunity compared to healthy controls (13), as confirmed in a larger study still in preprint (19).…”

Immunosuppression and SARS-CoV-2 breakthrough infections

“… 4 , 5 , 6 Furthermore, the absence of anti-spike antibodies 4–6 weeks after the second dose of COVID-19 vaccine is associated with a 3·6 times increase in breakthrough infection compared with presence of robust humoral responses. 7 Thus, risk of breakthrough infection after COVID-19 vaccination among people with immune-mediated inflammatory diseases could correlate with poor antibody responses from specific immunosuppressive medications.…”

Immunogenicity, breakthrough infection, and underlying disease flare after SARS-CoV-2 vaccination among individuals with systemic autoimmune rheumatic diseases

“…A large prospective cohort study in India linked humoral vaccine response to clinical outcomes for breakthrough infections among SARDs 35 . This prospective cohort study enrolled 630 patients with SARDs and measured anti-RBD antibodies 4-6 weeks after the 2nd vaccine dose 35 . They categorized patients based on the anti-RBD level as having a good response, inadequate response, or no response 35 .…”

“…This prospective cohort study enrolled 630 patients with SARDs and measured anti-RBD antibodies 4-6 weeks after the 2nd vaccine dose 35 . They categorized patients based on the anti-RBD level as having a good response, inadequate response, or no response 35 . They contacted each patient every two months to identify COVID-19 cases.…”