Impaired Neutralization of SARS-CoV-2 Including Omicron Variants after COVID-19 mRNA Booster Immunization under Methotrexate Therapy (preprint)

ABSTRACT

ABSTRACT Objective To determine the immediate need for a fourth COVID-19 vaccination based on the neutralizing capacity in patients on methotrexate (MTX) therapy after mRNA booster immunization. Methods In this observational cohort study, neutralizing serum activity against SARS-CoV-2 wildtype (Wu01) and variant of concern (VOC) Omicron BA.1 and BA.2 were assessed by pseudovirus neutralization assay before, 4 and 12 weeks after mRNA booster immunization in 50 rheumatic patients on MTX, 26 of whom paused the medication. 44 non-immunosuppressed persons (NIP) served as control group. Results While the neutralizing serum activity against SARS-CoV-2 Wu01 and Omicron variants increased 67-to 73-fold in the NIP after booster vaccination, the serum activity in patients receiving MTX increased only 20-to 23-fold. As a result, significantly lower neutralizing capacities were measured in patients on MTX compared to the NIP at week 4. Patients who continued MTX treatment during vaccination had significantly lower neutralizing serum titres against all three virus strains at week 4 and 12 compared to patients who paused MTX and the control group, except for BA.2 at week 12. Patients who paused MTX reached comparably high neutralization titres as the NIP, except for Wu01 at week 12. Neutralization of omicron variants was significantly lower in comparison to wildtype in both groups. Conclusion Patients pausing MTX showed a similar vaccine response to NIP. Patients who continued MTX demonstrated an impaired booster response indicating a potential benefit of a second booster vaccination.