ABSTRACT
BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.
Subject(s)
COVID-19 , RNA Viruses , Humans , Neutralization Tests , COVID-19 Testing , COVID-19/diagnosis , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Background: Several research groups have recently described a reduced vaccination response to COVID-19 vaccination under methotrexate (MTX) (1,2). The increase in humoral immune response when pausing MTX two weeks after vaccination has already been described for infuenza vaccination (3). However, data regarding MTX-hold during COVID-19 vaccination are still lacking. Objectives: To study the effect of MTX and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods: In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 rheumatic patients on methotrexate therapy, 31 of whom temporarily paused medication without a fxed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication. Results: MTX patients showed a signifcantly lower mean antibody response compared to AIRD patients without immunosuppressive therapy (71.8 % vs 92.4 %, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49;p<0.001). All nine patients with antibody levels below the cutoff were older than 60 years. Patients who held MTX during at least one vaccination showed signifcantly higher mean neutralising antibody levels after second vaccination, compared to patients who continued MTX therapy during both vaccinations (83.1 % vs 61.2 %, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8 % vs 51.9 %, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. Conclusion: MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination signifcantly improves the antibody response in patients over 60 years of age.