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

ObjectiveTo 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. MethodsIn 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. ResultsWhile 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. ConclusionPatients 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.

Pausing methotrexate improves immunogenicity of COVID-19 vaccination in patients with rheumatic diseases

ObjectiveTo 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). MethodsIn 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 fixed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication. ResultsMTX patients showed a significantly 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 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 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. ConclusionMTX 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.

Risk stratification following complex PCI: clinical versus anatomical risk stratification including "post PCI residual SYNTAX-score" as quantification of incomplete revascularization.

BACKGROUND: EuroSCORE and completeness of revascularization predicts long-term survival after multivessel PCI (MV-PCI). The SYNTAX-Score has also been proposed to predict clinical outcome. The prognostic impact of these scores to predict long-term survival after PCI has not yet been compared. METHODS AND RESULTS: Long-term survival was assessed in 740 patients undergoing MV-PCI. We calculated EuroSCORE, SYNTAX-Score, STS-Score, the clinical SYNTAX-Score (CSS), and the "post-PCI residual SYNTAX-Score." Mean follow-up time was 4.5 ± 2.5 years. 341 patients (46%) were treated for ACS (STEMI N = 191; NSTEMI N = 150). 113 patients (15%) underwent PCI of left main coronary artery. The EuroSCORE was significantly lower for stable patients compared to patients with ACS (stable 4.1 ± 4.5, NSTEMI 13.9 ± 13.3, STEMI 18.1 ± 18.7, p < 0.001). The differences in the SYNTAX-Score were less obvious but even significant (stable 14.9 ± 8.6, NSTEMI 17.8 ± 9.9, STEMI 18.3 ± 9.0; p < 0.001). Patients in the highest tertiles of each risk score experienced a dramatically elevated mortality rate compared to the extremely low mortality rate in the lower tertiles (p log-rank <0.001). This comparison remained significant for the EuroSCORE and STS-Score but not for the SYNTAX-Score, when analysis was restricted to stable patients. The multivariate Cox-regression-analysis confirmed the logistic EuroSCORE, EuroSCORE II, and the STS-Score as independent predictors of long-term mortality, whereas the SYNTAX-Score (including residual form) and the CSS had no predictive value. CONCLUSION: The EuroSCORE and the STS-Score outperforms the SYNTAX-Score and the CSS in predicting long-term survival following MV-PCI. In addition, the residual SYNTAX-Score predicts long-term survival not independently.