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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-338401

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, with the exception of BA.2 at week 12. Patients who paused MTX reached comparably high neutralization titres as the NIP, with the exception of 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.

2.
J Clin Med ; 11(6)2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1760679

ABSTRACT

Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.

3.
Ann Rheum Dis ; 81(6): 881-888, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1741593

ABSTRACT

OBJECTIVE: To study the effect of methotrexate (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 patients with AIRD on MTX therapy, 31 of whom temporarily paused medication without a fixed regimen. The control group consisted of 21 patients with AIRD without immunosuppressive medication. RESULTS: Patients on MTX showed a significantly lower mean antibody response compared with patients with AIRD 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 cut-off were older than 60 years. Patients who held MTX during at least one vaccination showed significantly higher mean neutralising antibody levels after second vaccination, compared with 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 significantly improves the antibody response in patients over 60 years of age.


Subject(s)
Autoimmune Diseases , COVID-19 , Rheumatic Diseases , Aged , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunogenicity, Vaccine , Methotrexate/therapeutic use , Middle Aged , Retrospective Studies , Rheumatic Diseases/drug therapy , SARS-CoV-2 , Vaccination
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