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Objective: Currently, there are no data available on SARS-CoV-2 vaccine responses in pediatric-onset multiple sclerosis (POMS), and little is known about the course of SARS-CoV-2 infection in this age group. We therefore investigated humoral immune responses after COVID-19 vaccination and/or infection in POMS., Methods: We retrospectively analyzed seroconversion rates and SARS-CoV-2-specific antibody levels in 30 POMS and one pediatric CIS patient treated with no disease-modifying therapy (no DMT), immunomodulatory DMT (IM-DMT), or immunosuppressive DMT (IS-DMT) from two Austrian MS centers., Results: The median age at MS onset was 15.39 years (interquartile range [IQR]: 1.97). The median age at the first COVID-19 vaccination was 17.43 years (IQR: 2.76). After two vaccine doses, seroconversion (≥0.8 BAU/ml) was reached in 25 of 28 patients (89.3%). All patients with no DMT or IM-DMT generated robust immune responses to vaccination (seroconversion: no DMT: 6/6, IM-DMT: 7/7 [100%]; median titers: no DMT: 2075 BAU [IQR: 1268.50], IM-DMT: 2500 BAU [IQR: 0]). In the IS-DMT group, seroconversion was achieved in 12 of 14 patients (80%), and median titers were 50.8 BAU (IQR 254.63). Titers were significantly higher in no DMT versus IS-DMT (P = 0.012) and in IM-DMT versus IS-DMT (P = 0.001). Infection with SARS-CoV-2 occurred in 11 of 31 patients, and symptoms were mild in all cases. One relapse occurred after infection, but no relapses were documented after vaccination., Conclusions: Generally, mRNA vaccinations were well tolerated in POMS patients with and without DMT. Immune response was significantly reduced in patients treated with IS-DMT. No unexpected adverse events or relapses related to vaccinations were observed., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A 3 rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed. Currently it remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses., Methods: 50 patients under immunosuppression and 42 healthy controls (HCs) received a 3 rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3 rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period., Results: At week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781-10,208] versus 9650 BAU/ml [6633-16,050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological disease-modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported., Conclusion: Due to a fast decline in anti-RBD antibodies in IMID patients an early 4 th vaccination should be considered in this vulnerable group of patients., Competing Interests: Declaration of competing interest DM reports support for meeting attendances from Pfizer and consultation fees from AstraZeneca; JS reports about grants, consulting and personal fees from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB and grants from Abbvie, AstraZeneca, Lilly, Novartis, and Roche; HR received speaker fees from Gilead, Merck Sharp and Pfizer and travel support from Janssen; HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis; DA received grants, speaker fees, or consultancy fees from Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi; RK reports consulting fees from AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag and speaker fees from Otsuka; ES received travel support from Pfizer, Bristol-Myers Squibb and Boehringer-Ingelheim and speaker fees from Lilly; MB reports about personal fees from Eli-Lilly. All other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Patients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development., Methods: In this open-label extension trial, 37 rituximab-treated patients who received a third dose with either a vector or mRNA-based vaccine were vaccinated a fourth time with an mRNA-based vaccine (mRNA-1273 or BNT162b2). Key endpoints included the humoral and cellular immune response as well as safety after a fourth vaccination., Results: The number of patients who seroconverted increased from 12/36 (33%) to 21/36 (58%) following the fourth COVID-19 vaccination. In patients with detectable antibodies to the spike protein's receptor-binding domain (median: 8.0 binding antibody units (BAU)/mL (quartiles: 0.4; 13.8)), elevated levels were observed after the fourth vaccination (134.0 BAU/mL (quartiles: 25.5; 1026.0)). Seroconversion and antibody increase were strongly diminished in patients who received rituximab treatment between the third and the fourth vaccination. The cellular immune response declined 12 weeks after the third vaccination, but could only be slightly enhanced by a fourth vaccination. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred., Conclusions: A fourth vaccine dose is immunogenic in a fraction of rituximab-treated patients. Continuation of rituximab treatment reduced humoral immune response, suggesting that rituximab affects a second booster vaccination. It might therefore be considered to postpone rituximab treatment in clinically stable patients., Trial Registration Number: 2021-002348-57., Competing Interests: Competing interests: PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB. MB reports about personal fees from Eli-Lilly, DA received grants and consulting fees from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz. JSS reports about grants, consulting and personal fees from AbbVie, Astra-Zeneca, Lilly, Novartis, Amgen, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung and UCB. DM received support for meeting attendances from Pfizer. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis. AK reports about speaker and consulting fees from AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis and Pfizer. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Impaired response to COVID-19 vaccination is of particular concern in immunosuppressed patients. To determine the best vaccination strategy for this vulnerable group we performed a single center, 1:1 randomized blinded clinical trial. Patients who failed to seroconvert upon two mRNA vaccinations (BNT162b2 or mRNA-1273) are randomized to receive either a third dose of the same mRNA or the vector vaccine ChAdOx1 nCoV-19. Primary endpoint is the difference in SARS-CoV-2 spike antibody seroconversion rate between vector and mRNA vaccinated patients four weeks after the third dose. Secondary outcomes include cellular immune responses. Seroconversion rates at week four are significantly higher in the mRNA (homologous vaccination, 15/24, 63%) as compared to the vector vaccine group (heterologous vaccination, 4/22, 18%). SARS-CoV-2-specific T-cell responses are reduced but could be increased after a third dose of either vector or mRNA vaccine. In a multivariable logistic regression analysis, patient age and vaccine type are associated with seroconversion. No serious adverse event is attributed to COVID-19 booster vaccination. Efficacy and safety data underline the importance of a booster vaccination and support the use of a homologous mRNA booster vaccination in immunosuppressed patients.Trial registration: EudraCT No.: 2021-002693-10., (© 2022. The Author(s).)

Patients suffering from autoimmune hepatitis, a chronic immune-mediated liver disease with an incidence of 0.9 to 2 per 100,000 population per year in Europe, are considered to have a particularly increased risk for coronavirus disease 2019 (Covid-19)-associated hospitalization and death. 1,2 Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination provides an essential tool to reduce morbidity and mortality in this cohort. However, a large multicenter study in China has shown a lower immunogenic response to inactivated whole-virion SARS-CoV-2 vaccines of chronic liver disease patients in comparison with the healthy population. 3 Furthermore, reports from inflammatory bowel diseases or rheumatic disorders showed a reduced serologic response in patients taking glucocorticoids or thiopurine. 4,5 The decrease in vaccine-induced antibodies over time, as well as the emergence of variants of concern, led to the recommendation of an additional vaccination in immunocompromised patients., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To assess the humoral response to messenger RNA (mRNA) vaccine of patients with systemic autoimmune rheumatic disease (SARD) and the effect of immunosuppressive medication in a matched cohort study., Methods: Patients with SARD were enrolled and matched 1:1 for sex and age with healthy control (HC) subjects. Differences in humoral response to two doses of an mRNA vaccine in terms of seroconversion rate (SCR) and SARS-CoV-2 antibody level between the two groups and the impact of treatment within patients with SARD were assessed., Results: We enrolled 82 patients with SARD and 82 matched HC. SCR after the first dose was lower among the patient group than that of HC (65% compared with 100% in HC, p<0.0001) but levelled up after the second dose (94% vs 100%). After the second dose, SCR was lower for patients on combination disease-modifying antirheumatic drug (DMARD) therapy compared with all other groups (81% compared with 95% for monotherapy, p=0.01; 100% for both no DMARD therapy and HC, both p<0.0001). In addition, antibody levels after both doses were lower in patients compared with HC. We found that vaccination response was determined primarily by the number of DMARDs and/or glucocorticoids received, with patients receiving combination therapy (dual and triple therapy) showing the poorest response., Conclusions: Patients with SARD showed a good response after the second vaccination with an mRNA vaccine. However, the choice of immunosuppressive medication has a marked effect on both SCR and overall antibody level, and the number of different immunomodulatory therapies determines vaccination response., Competing Interests: Competing interests: PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB, outside the submitted work. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis. JS is the President of the Austrian Society of Rheumatology and Rehabilitation (unpaid position). HB received consulting fees from MSD, Pfizer, Takeda and Gilead, speaker fees from Shionogi, Pfizer and MSD, and advisory boards for Valneva, MSD and Gilead. DA reports grants from AbbVie, Amgen, Lilly, Novartis, Roche, SoBi and Sanofi, and other from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz, outside the submitted work. SB reports personal fees from AbbVie and Novartis, outside the submitted work. ES reports support for meeting attendances from Pfizer and Bristol Myers Squibb. HR, TK, DM, TN, TP, FW, SW and ST have nothing to declare., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: SARS-CoV-2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination., Methods: In this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4., Results: Seroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed., Conclusions: This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen., Competing Interests: Competing interests: BK has received honoraria for lecturing/consulting from Biogen, BMS Celgene, Johnson & Johnson, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB. MB reports about personal fees from Eli-Lilly. DA received grants and consulting fees from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz. JSS reports about grants, consulting and personal fees from AbbVie, Astra-Zeneca, Lilly, Novartis, Amgen, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung and UCB. KS received a research grant from Pfizer. MZ received grants and consulting fees from Nabriva, AntibioTxApS, Shionogi, NovoNordisk, Merck, Infectopharm and Pfizer. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response., Methods: We enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response., Results: Samples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC., Conclusions: Patients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy., Competing Interests: Competing interests: PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis. JS is the President of the Austrian Society of Rheumatology and Rehabilitation (unpaid position). HB received consulting fees from MSD, Pfizer, Takeda and Gilead, speaker fees from Shionogi, Pfizer and MSD, advisory boards for Valneva, MSD and Gilead. DA reports grants from AbbVie, Amgen, Lilly, Novartis, Roche, SoBi and Sanofi, other from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz, outside the submitted work. SB reports personal fees from AbbVie and personal fees from Novartis, outside the submitted work. ES reports support for meeting attendances from Pfizer and Bristol Myers Squibb., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) is currently finally determined in laboratory settings by real-time reverse-transcription polymerase-chain-reaction (rt-PCR). However, simple testing with immediately available results are crucial to gain control over COVID-19. The aim was to evaluate such a point-of-care antigen rapid test (AG-rt) device in its performance compared to laboratory-based rt-PCR testing in COVID-19 suspected, symptomatic patients., Methods: For this prospective study, two specimens each of 541 symptomatic female (54.7%) and male (45.3%) patients aged between 18 and 95 years tested at five emergency departments (ED, n = 296) and four primary healthcare centres (PHC, n = 245), were compared, using AG-rt (positive/negative/invalid) and rt-PCR (positive/negative and cycle threshold, Ct) to diagnose SARS-CoV-2. Diagnostic accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive value (NPV), and likelihood ratios (LR+/-) of the AG-rt were assessed., Results: Differences between ED and PHC were detected regarding gender, age, symptoms, disease prevalence, and diagnostic performance. Overall, 174 (32.2%) were tested positive on AG-rt and 213 (39.4%) on rt-PCR. AG correctly classified 91.7% of all rt-PCR positive cases with a sensitivity of 80.3%, specificity of 99.1%, PPV of 98.3, NPV of 88.6%, LR(+) of 87.8, and LR(-) of 0.20. The highest sensitivities and specificities of AG-rt were detected in PHC (sensitivity: 84.4%, specificity: 100.0%), when using Ct of 30 as cut-off (sensitivity: 92.5%, specificity: 97.8%), and when symptom onset was within the first three days (sensitivity: 82.9%, specificity: 99.6%)., Conclusions: The highest sensitivity was detected with a high viral load. Our findings suggest that AG-rt are comparable to rt-PCR to diagnose SARS-CoV-2 in COVID-19 suspected symptomatic patients presenting both at emergency departments and primary health care centres., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Roche Diagnostics provided support for this study in the form of funds sent to the scientific association Science Center Donaustadt, which were used to cover the costs of the test materials and statistician. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation., Methods: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls., Results: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19 + peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response., Conclusions: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure ( p = 0.003), positively tested family members ( p = 0.04), and travel history ( p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose ( p = 0.002) and altered taste or smell ( p < 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.

Background and objective: This prospective cohort study analyzed the immune response to COVID-19 mRNA vaccines in lung transplant recipients (LuTRs) compared to healthy controls (HCs) at a 6-month follow-up. Methods: After the first two doses of either BNT162b2 or mRNA-1273, SARS-CoV-2 antibodies were measured in LuTRs (n = 57) and sex- and age-matched HCs (n = 57). Antibody kinetics during a 6-month follow-up and the effect of a third vaccine dose were evaluated. Humoral responses were assessed using the Elecsys® Anti-SARS-CoV-2 S immunoassay. In 16 LuTRs, SARS-CoV-2-specific T cell responses were quantified using IFN-γ ELISpot assays. Results: Seroconversion rates were 94% and 100% after the first and second vaccine dose, respectively, in HCs, while only 19% and 56% of LuTRs developed antibodies. Furthermore, 22 of 24 LuTRs who received the third vaccine dose showed seroconversion (five of seven primary non-responders and 17 of 17 primary responders). A T cell response against SARS-CoV-2-spike S1 and/or S2 was detected in 100% (16/16) of HCs and 50% (8/16) of LuTRs. Conclusions: The data suggest that LuTRs have reduced humoral and cellular immune responses after two doses of COVID-19 mRNA vaccination when compared to HCs. A third dose may be of substantial benefit. [ABSTRACT FROM AUTHOR]

Background: Two years into the pandemic, vaccination remains the most effective option to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preliminary studies suggest vaccination efficacy in patients with inflammatory bowel diseases (IBD), but little is known about its impact on chronic intestinal inflammation. Here we assessed the mucosal inflammatory activity in patients with IBD before and after immunization with the mRNA-1273 (Moderna) vaccine by measurement of fecal calprotectin (fCP). Methods: In 42 patients with IBD, the baseline fCP levels obtained prior to the first vaccine were compared with the highest levels measured during and after two doses of vaccination. Patients' sera were collected after the second dose to evaluate anti-SARS-CoV-2 antibodies' titers. Results: We observed a significant fCP elevation in 31% of patients after any dose. Vedolizumab was identified as the only agent associated with an fCP increase (OR 12.4, 95% CI [1.6; 120.2], p = 0.0171). Gastrointestinal adverse events were reported in 9.5% of all subjects and in 75% of cases accompanied by an fCP increase. Anti-SARS-CoV-2 antibodies associated only weakly with the fCP increase after the first dose (p = 0.04). Conclusions: Our findings support possible collinearity in pathways of SARS-CoV-2 antigen expression and the pathogenesis of IBD. [ABSTRACT FROM AUTHOR]

Simple Summary: Here we confirm lower humoral and cellular responses in hematological patients compared with controls and highlight the response in risk-groups such as CAR-T-cell recipients. The main risk factor for a poor humoral response was anti-CD20 therapy. CD19+ B-cell and CD4+ T-cell levels were shown to be additional predictive markers for seroconversion. Further, we demonstrate a decline in antibodies over six months in responders and controls, and question if second vaccination non-responders benefit from of a third vaccination. Here we analyzed SARS-CoV-2-specific antibodies and T-cell responses after two coronavirus disease 2019 vaccinations over a six-month period in patients with hematological malignancies and assessed the effect of a third vaccination in a subgroup. Sixty-six patients and 66 healthy controls were included. After two vaccinations seroconversion was seen in 52% and a T-cell-specific response in 59% of patients compared with 100% in controls (p = 0.001). Risk factors for a poor serological response were age (<65a), history of anti-CD20 therapy within the year preceding vaccination, CD19+ B-cells < 110/µL, and CD4+ T-cells > 310/µL. The magnitude of T-cell response was higher in patients <65a and with CD19+ B-cells < 110/µL. Patients and healthy controls demonstrated a significant decrease in SARS-CoV-2 S antibody levels over the period of six months (p < 0.001). A third vaccination demonstrated a strong serological response in patients who had responded to the previous doses (p < 0.001). The third vaccination yielded seroconversion in three out of 19 patients in those without serological response. We conclude that both humoral and cellular responses after SARS-CoV-2 immunization are impaired in patients with hematological malignancies. A third vaccination enhanced B-cell response in patients who previously responded to the second vaccination but may be of limited benefit in patients without prior seroconversion. [ABSTRACT FROM AUTHOR]

Objective: The study was undertaken to assess the impact of B cell depletion on humoral and cellular immune responses to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccination in patients with various neuroimmunologic disorders on anti‐CD20 therapy. This included an analysis of the T cell vaccine response to the SARS‐CoV‐2 Delta variant. Methods: We investigated prospectively humoral and cellular responses to SARS‐CoV‐2 mRNA vaccination in 82 patients with neuroimmunologic disorders on anti‐CD20 therapy and 82 age‐ and sex‐matched healthy controls. For quantification of antibodies, the Elecsys anti‐SARS‐CoV‐2 viral spike (S) immunoassay against the receptor‐binding domain (RBD) was used. IFN‐gamma enzyme‐linked immunosorbent spot assays were performed to assess T cell responses against the SARS‐CoV‐2 Wuhan strain and the Delta variant. Results: SARS‐CoV‐2‐specific antibodies were found less frequently in patients (70% [57/82]) compared with controls (82/82 [100%], p < 0.001). In patients without detectable B cells (<1 B cell/mcl), seroconversion rates and antibody levels were lower compared to nondepleted (≥1 B cell/mcl) patients (p < 0.001). B cell levels ≥1 cell/mcl were sufficient to induce seroconversion in our cohort of anti‐CD20 treated patients. In contrast to the antibody response, the T‐cell response against the Wuhan strain and the Delta variant was more pronounced in frequency (p < 0.05) and magnitude (p < 0.01) in B‐cell depleted compared to nondepleted patients. Interpretation: Antibody responses to SARS‐CoV‐2 mRNA vaccinnation can be attained in patients on anti‐CD20 therapy by the onset of B cell repopulation. In the absence of B cells, a strong T cell response is generated which may help to protect against severe coronavirus disease 2019 (COVID‐19) in this high‐risk population. ANN NEUROL 2022;91:342–352 [ABSTRACT FROM AUTHOR]