ABSTRACT
Background: The interplay between humoral and cellular response after vaccination against SARS-CoV-2 in patients (pts.) with autoimmune infammatory rheumatic diseases (AIRD) remains unknown. Objectives: To investigate the impact of different immunosuppressive therapies on the development of humoral and cellular immune responses to full 2-dose SARS-CoV-2 vaccination in AIRD pts. with stable low disease activity. Methods: The immune reactivity to COVID-19 vaccination was investigated in a prospectively recruited AIRD cohort with rheumatoid arthritis, axial spondy-loarthritis or psoriatic arthritis which received a therapy with IL-17i, TNFi, JAKi or MTX (alone or in combination). Almost all patients received mRNA-based vaccine, only 4 patients had a heterologous scheme. Anti-spike(S) antibodies(ab.) and sera neutralizing capacity (neutralization dilution 50;ND50) were measured 4 weeks after the frst (prime+4w) and 4 weeks after the second vaccination (boost+4w). Vaccine-specifc cellular immunity was evaluated by quantifying expression of activation markers on T cells as well as their production of key cytokines, at prime+4w and boost+4w. Results: Overall, a total of 92 pts. were included in the fnal cohort. 31 (33.7%) pts. were on TNFi, 24 (26.1%) on IL-17i, 24 (26.1%) on JAKi, each group encompassing pts. receiving drug inhibitors alone or in combination with MTX.13 (14.1%) were treated with MTX alone. The median time between the vaccination and blood sampling was 31 [IQR: 28-34] days after prime+4w and 28 [IRQ: 28-28] days after boost+4w. Although at prime+4w only 34/90 (37.8%) of pts. presented neutralizing ab., the majority (86/91, 94.5%), developed them at boost+4w. The highest neutralization titer developed the pts. on IL-17i both at prime+4w (74 [IQR: 13-91]) and boost+4w (798 [IQR: 511-1344]), while no statistically signifcant differences were found in the neutralization titer at boost+4w for the TNFi, JAKi, and MTX groups: 207 ND50 [IQR: 120-576], 319 [IQR: 133-461] and 749 [IQR: 264-1920], respectively. 81/90 (90.0%) pts. developed IgG ab. against SARS-CoV-2 S-protein at prime+4w and 91/92 (98.9%) at boost+4w. Pts. receiving IL-17i developed higher ab. titers (8295 U/mL [IQR: 4586-11,237]) compared to the other three groups: JAKi (4405 U/mL [IQR: 1436-7265], TNFi (2313 [IQR: 1156-3630] U/mL) and MTX (2010 U/mL [IQR: 693-9254]). Neutralization capacity correlated well with the titer of anti-S ab. at both timepoints. Co-administration of biologic/tsDMARDs and MTX led to lower titers compared to biologic/tsDMARDs mon-otherapy. All therapies left frequencies of CD154+CD137+ CD4+ T cells and CD137+ CD8+ T cells at prime+4w and boost+4w unchanged. Polyfunction-ality and T cell cytokine profiles across therapies did not signifcantly vary at boost+4w. Conclusion: Even after insufficient seroconversion for neutralizing capacity and ab. response against SARS-CoV-2 S-proteins between pts. of different mod of action agents, particularly for MTX and JAKi after frst vaccination, a second vaccination covered almost all pts. regardless of DMARDs therapy, with better outcomes in those on IL-17I. T cell immunity revealed similar frequencies of activated T cells in all modes of action after the second vaccination.
ABSTRACT
The severe acute respiratory coronavirus type 2 (SARS-CoV-2) pandemic is keeping most countries of the world in suspense. In Germany the prevalence of SARS-CoV2 infections is under 2% but for weeks the numbers in Germany have also been increasing. The care in rheumatology was temporarily impaired by the first wave of the pandemic. This article reports the infection situation in the largest specialized rheumatology clinic in Germany, the Rheumatism Center Ruhrgebiet, because recently during the second wave for the first time several SARS-CoV2 infections occurred here over one weekend, which led to considerable anxiety in many of those involved. The situation could be clarified by consistent testing of patients and personnel with the rapid antigen test and the situation could be mollified. Ultimately, only a few persons were tested positive and the courses by the patients have so far remained bland. This shows the effectiveness of the protective hygiene measures consistently implemented since April.