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
Introduction: The optimal management of COVID-19 in transplant patients is not defined so far. The major concern is the ability of transplant patients to generate a sufficient antiviral response under immunosuppressive treatment. Methods: Here, we analysed T-cell immunity directed against Spike, Membrane and Nucleocapsid proteins of SARS-CoV-2 in a small cohort of 6 transplant patients (TP) with COVID-19 in comparison to 28 non-immunosuppressed patients (NIP). Results: The median patient age of transplant cohort (3 renal transplant, 1 lung, and 1 combined liver-kidney and 1 pancreas-kidney) as well as gender did not differ from NIP. We also did not find statistical differences for the time between the diagnosis of COVID-19 and analysis of T-cell immunity between the two cohorts. Notably, despite immunosuppressive therapy, we were able to detect a strong antiviral response in transplant patients. TP generated SARSCoV-2 reactive T-cells against all three proteins with predominance of CD4 + T cells with pro-inflammatory Th1 phenotype. Moreover, SARS-CoV-2 reactive CD4 + and CD8 + T cells were able to produce multiple pro-inflammatory cytokines demonstrating their potential protective capacity. Of interest, the frequencies and cytokine production patterns of SARS-CoV-2 reactive T-cells did not show any differences between TP and NIP. Conclusion: A strong polyfunctional T-cell response directed against all three SARS-CoV-2 proteins can be generated in transplant despite immunosuppressive treatment. In comparison to non-immunosuppressed patients, the antiviral immunity is non-inferior. Since the dosage of immunosuppression in analysed patients was reduced, further studies are required to assess the antiviral immunity under standard immunosuppression.
ABSTRACT
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused unprecedented public health and economical challenges worldwide. Cellular immunity is known to be crucial for the virus clearance. Recent data demonstrate pre-existing SARS-CoV-2-reactive T cells in samples of healthy blood donors collected before SARS-CoV-2 pandemics. The presence of these potentially protective T cells in SARS-CoV-2 naive population can be explained by cross-reactivity to the endemic common cold coronavirus. Whether such cells are also detectable in immunosuppressed patients is not known so far. Methods: We analysed the presence of SARS-CoV-2-cross-reactive T cell immunity in samples of 10 renal transplant patients (RTX) collected in 2019 before the onset of SARS-CoV-2 pandemics. Samples of 10 non-immunosuppressed/ immune competent SARS-CoV-2 naive patients matched to transplant patients were analysed as controls. T-cell reactivity against Spike-, Nucleocapsid-, and Membrane-SARS-CoV-2 proteins were analysed by multiparameter flow cytometry. Results: 50% of analysed RTX showed CD4 + T-cells reactive against at least one SARS-CoV-2 protein. CD8 + T cells reactive against at least one SARSCoV2 protein were demonstrated in 30% of RTX. Notably, the detected cells were of differentiated memory phenotype producing several Th1 cytokines including IFNg, TNFa, IL-2, as well as Granzyme B. The frequencies and cytokine expression pattern of SARS-CoV-2 reactive T-cells did not differ between transplant and non-transplant cohorts. Conclusion: Despite immunosuppressive treatment and underlined renal disease, transplant patients were able to generate cellular immunity crossreactive to SARS-CoV-2. The magnitude and functionality of the pre-existing immunity was non-inferior compared to the immune competent cohort. Although several pro-inflammatory cytokines were produced by the detected T cells, further studies are required to prove their antiviral protection.