Pausing methotrexate prevents impairment of Omicron BA.1 and BA.2 neutralisation after COVID-19 booster vaccination

Abstract

ObjectiveThe level of neutralising capacity against Omicron BA.1 and BA.2 after third COVID-19 vaccination in patients on paused or continuous methotrexate (MTX) therapy is unclear.MethodsIn this observational cohort study, neutralising serum activity against SARS-CoV-2 wild-type (Wu01) and variant of concern Omicron BA.1 and BA.2 were assessed by pseudovirus neutralisation assay before, 4 and 12 weeks after mRNA booster immunisation in 50 rheumatic patients on MTX, 26 of whom paused the medication. 44 non-immunosuppressed persons (NIP) served as control group.ResultsWhile the neutralising serum activity against SARS-CoV-2 Wu01 and Omicron variants increased 67–73 fold in the NIP after booster vaccination, the serum activity in patients receiving MTX increased only 20–23 fold. Patients who continued MTX treatment during vaccination had significantly lower neutralisation against all variants at weeks 4 and 12 compared with patients who paused MTX and the control group, except for BA.2 at week 12. Patients who paused MTX reached comparably high neutralising capacities as NIP, except for Wu01 at week 12. The duration of the MTX pause after—not before—was associated with a significantly higher neutralisation capacity against all three variants, with an optimal duration at 10 days after vaccination.ConclusionPatients pausing MTX after COVID-19 booster showed a similar vaccine response to NIP. Patients who continued MTX demonstrated an impaired response indicating a potentially beneficial second booster vaccination. Our data also suggest that a 1 week MTX break is sufficient if the last administration of MTX occurs 1–3 days before vaccination.

Importance of SARS-CoV-2 Spike Antibodies and B Cell Reconstitution to Optimize the Prevention Strategy of COVID-19

“…Finally, concomitant treatment with methotrexate may further decrease the possibility of seroconversion. [5][6][7] The majority of these data were obtained from patients after 2 doses of the vaccine, whereas booster doses of the SARS-CoV-2 vaccines have since emerged as an important strategy for containing the pandemic. The majority of patients have now received 3 to 4 doses of vaccine, and a fifth dose may even be discussed in severely immunocompromised patients.…”

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients

“…The abrogated immunological response to the primary vaccination schedule results in a faster decline of post-vaccination immunity in IA patients [ 5 , 7 , 16 , 18 , 25 , 26 ], making booster vaccinations among IA patients even more important than in HC. Current studies proved that, though COVID-19 booster vaccinations are effective in IA patients [ 27 , 28 , 29 ], also the immunogenicity of the booster dose is impaired in this group of patients [ 15 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. There are only single studies evaluating the effect of immunomodulatory drugs on the immunogenicity of the booster dose against COVID-19, indicating worsen response after GCs [ 30 ], biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) [ 15 , 30 ], and MTX [ 34 , 35 ].…”

“…Current studies proved that, though COVID-19 booster vaccinations are effective in IA patients [ 27 , 28 , 29 ], also the immunogenicity of the booster dose is impaired in this group of patients [ 15 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. There are only single studies evaluating the effect of immunomodulatory drugs on the immunogenicity of the booster dose against COVID-19, indicating worsen response after GCs [ 30 ], biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) [ 15 , 30 ], and MTX [ 34 , 35 ]. In our previous study, we assessed the effect of immunomodulatory drugs on humoral and cellular responses after the booster dose [ 36 ].…”

Methotrexate inhibition of SARS-CoV-2 entry, infection and inflammation revealed by bioinformatics approach and a hamster model

“…Recent studies raised discussion on its role of COVID-19, such as whether patients receiving MTX therapy ( e.g. , RA patients) would discontinuation on immune response after COVID-19 vaccination ( 12 ), and mechanism-based hypothesis to test MTX against COVID-19 in vitro ( 13 , 14 ). While its mechanisms for treating COVID-19 are remaining unclear.…”