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Patients undergoing treatment for haematological malignancies have been shown to have reduced antibody responses to vaccination against SARS-COV2. This is particularly important in patients who have undergone allogeneic haemopoietic stem cell transplantation (HSCT), in whom there is limited data about vaccine efficacy. In this retrospective single-centre analysis, we present data on serologic responses following one, two, three or four doses of either Pfizer-BioNTech (PB), AstraZeneca (AZ) or Moderna (MU) SARS-CoV- 2 vaccines from a series of 75 patients who have undergone allogeneic HSCT within 2 years from the time they were revaccinated. The seroconversion rates following post-HSCT vaccination were found to be 50.7%, 78%, 79% and 83% following the first, second, third and fourth primary post -HSCT vaccine doses, respectively. The median time from allograft to first revaccination was 145 days (range 79-700). Our findings suggest that failure to respond to the first SARS-CoV- 2 vaccine post-HSCT was associated with the presence of acute GVHD (p = 0.042) and treatment with rituximab within 12 months of vaccination (p = 0.019). A statistical trend was observed with the presence of chronic GVHD and failure to seroconvert following the second (p = 0.07) and third (p = 0.09) post-HSCT vaccine doses. Patients who had received one or more SARS-CoV- 2 vaccines prior to having an allogeneic stem cell transplant were more likely to demonstrate a positive antibody response following the first dose of revaccination against Sars-CoV- 2 (p = 0.019) and retained this seropositivity following subsequent doses. The incidence of confirmed COVID-19 diagnosis among this cohort at the time of analysis was 16%. 17% of these were hospitalised and there was one recorded death (8%) secondary to COVID-19 in a patient who was 15.7 months post allogeneic transplant. In summary, this study suggests that despite the initial low seroconversion rates observed postallogeneic transplant, increasing levels of antibody response are seen post the second primary vaccine dose. In addition, there seems to be lower risk of mortality secondary to COVID-19 in this vaccinated population, compared to what was reported in the earlier phases of the pandemic prior to use of SARS-COV2 vaccination. This adds support to the widely adopted policy of early full revaccination with repeat of primary vaccine doses and boosters post-HSCT to reduce mortality in this population. Finally, we have identified rituximab use and active GVHD as potential risk factors influencing serological responses to SARS-COV2 vaccination and further work should focus on further characterising this risk and optimum dosing schedule both pre-and post-transplant.
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This study compares the serological antibody level post-COVID-19 vaccine among healthy subjects and psychiatric patients on antidepressant therapy. It also examines the difference in antidepressants' side effects experienced by psychiatric patients following the completion of two vaccine doses. A comparative posttest quasi-experimental study was conducted among healthy subjects and psychiatric patients on antidepressant medication in a teaching hospital in Malaysia. Elecsys Anti-SARS-CoV-2 assay was used to detect the antibody titre between weeks 4 and 12 post vaccination. The antidepressant side-effect checklist (ASEC) was used to monitor the occurrence of antidepressant-related side effects pre-and post-vaccination. 24 psychiatric patients and 26 healthy subjects were included. There was no significant difference in the antibody level between the patients (median = 1509 u/ml) and the healthy subjects (median = 995 u/ml). There was no significant worsening in the antidepressant-related side effects. The antibody level post-COVID-19 vaccine did not differ significantly between patients on antidepressant therapy and healthy subjects. Additionally, there was no change in the antidepressant side effects experienced by the patients following the completion of the vaccine.Copyright © 2022, Research Trends (P) LTD.. All rights reserved.
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Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.
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BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022;33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRA APAP – n = 37RA APAP + n = 36p-valueHC APAP – n = 8HC APAP + n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07 (NS)45 (12)44 (14)0.90 (NS)Female sex, n (%)24 (65)19 (53)0.29 (NS)2 (25)5 (38)0.53 (NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19 (NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19 (NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56 (NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67 (NS)NANANADMARD therapycsDMARD-mono, n (%)13/37 (35)9/36 (25)0.35 (NS)NANANAbDMARD-mono/combo, n (%)16/37 (43)16/36 (44)0.92 (NS)NANANAtsDMARDs-mono/combo, n (%)8/37 (22)11/36 (31)0.38 (NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52 (NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39 (NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundUnderstanding the dynamics of humoral immunity after COVID-19 vaccination is crucial in developing vaccination strategies. Antibody response patterns are more complex in patients with rheumatoid arthritis (RA) because of their underlying autoimmunity and immunosuppressive medications. The kinetics of vaccine response in RA patients are not well understood.ObjectivesTo construct a model of antibody response to COVID-19 vaccination in patients with RA.MethodsTwo patient groups were included for the study. The first group was composed of RA patients who were enrolled for influenza vaccination study between Oct 6, 2021 and November 3, 2021, in whom serial serum samples were obtained 0, 4, 16 weeks after vaccination. The second group was consecutively enrolled from outpatient clinic between October 6, 2021 and June 3, 2022, in whom serum sample was obtained once. After collecting data on demographics, vaccination and infection history of COVID-19 were obtained by self-report via questionnaire and data from Korean center for disease control. We then measured antibody titers against receptor binding domain of spike protein (anti-RBD) and nucleocapsid (anti-N), using Chemiluminescence microparticle immunosaasy (Abbott, USA) and Electrochemiluminescence immunoassay (Roche, Germany) respectively. The anti-RBD titer was log-transformed to improve normality. Time from vaccination and log of anti-RBD titer was modeled using fractional polynomial. Covariates including age, sex, BMI, underlying disease and immunosuppressive drugs were analyzed using Generalized Estimating Equations to account for repeated measured from a subject.ResultsA total of 736 patients (1042 samples) were enrolled. After excluding patients who experienced COVID-19 infection before sampling (n=84), those unvaccinated (n=44) and uncertain COVID-19 infection history (n=59), the data on 778 samples from 549 patients were analyzed (Group 1: 125, Group 2: 424). Antibody titer reached peak at 12 days after vaccination and decreased exponentially (Figure 1) which fell to 36.5% from peak after 2 months. Compared to the first vaccination, the 3rd and 4th vaccination significantly shifted anti-RBD antibody response curve (28 times, 95% CI 4~195;32 times 95% CI 4~234, respectively). However, there was no significant shift after the 4th vaccination from the 3rd vaccination (p=0.6405). Multivariable analysis showed that number of vaccinations and sulfasalazine (coefficient: 0.40, 95% CI 0.12~0.68) increased vaccine response but age (coefficient: -0.03, 95% CI -0.04~-0.02), abatacept (coefficient: -2.07, 95% CI -3.30~-0.84) and, JAK inhibitor (coefficient: -0.82, 95% CI -1.34~-0.31) decreased vaccine response.ConclusionAnti-RBD response to COVID-19 vaccination showed a peak at 12 days after vaccination and then exponentially decreased in patient with RA. The antibody response is affected by age and medications used for the treatment of RA.Table 1.ln[RBD (U/ml)]coefficient (univariable)95% CIp-valuecoefficient (multivariable)95% CIp-valuesex (female)0.17-0.22, 0.550.393---age-0.02-0.03, -0.01<.001**-0.03-0.04, -0.02<.001**DM0.11-0.27, 0.500.568---HTN-0.38-0.69, -0.070.018*---CKD0.680.07, 1.290.030*---RA duration (yr)-0.04-0.06, -0.010.001**---Pd (mg/d)-0.06-0.11, 0.000.035*---MTX use-0.23-0.52, 0.050.105---HCQ use0.01-0.28, 0.290.965---SSZ use0.450.07, 0.840.022*0.400.12,0.680.005**LEF use0.00-0.37, 0.370.988---TNF inhibitors use0.29-0.16, 0.730.208---Abatacept use-2.07-3.14, -0.99<.001**-2.07-3.30, -0.840.001**JAK inhibitors use-0.88-1.52, -0.240.007**-0.82-1.34, -0.310.002**Time (months)log(t)-1.96-2.37, -1.54<.001**-1.90-2.29, -1.50<.001**t
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BACKGROUND: The coronavirus disease 2019 (COVID-2019) causes the severe contagious acute respiratory syndrome. Therefore, massive vaccination campaign is mandatory to control the spread. Sputnik COVID-19 vaccines induce immunity through different mechanisms involving antibody response that bind to the spike protein to neutralize the viral entry into the cells. AIM: This study aims to compare the titers of specific antibodies in the pre-and post-vaccination sera in the vaccinated Egyptian population to evaluate the efficacy of the sputnik vaccine. METHOD(S): Samples were collected from 205 adult volunteers receiving the Sputnik vaccine in the Reference Laboratory of Egyptian University Hospitals. Samples were collected before vaccination and within 1, 2, or 3 months after receiving two doses of Sputnik SARS-CoV-2 vaccines from August to October 2021, serum samples collected were tested by quantitative chemiluminescent immunoassay using (Mindray CL-960i chemiluminescence analyzer, India) at the Reference laboratory of Egyptian University Hospitals for neutralizing antibodies, anti-spike antibodies, and total antibody levels before and after vaccination. RESULT(S): The results of the 205 paired samples illustrated that there was a statistically significant difference between pre-and post-vaccination antibody levels with a p-value of (< 0.001) indicating that the vaccine produced significantly high levels of antibodies. CONCLUSION(S): COVID-19 Sputnik vaccines induce immunity through an antibody response that binds to the virus to neutralize its entry into cells. Our study showed a significant increase in the measured post-vaccination levels of the three antibodies among the enrolled volunteers compared to the basal pre-vaccination level and thus sputnik vaccine protects against SARS-CoV-2 infections.Copyright © 2023 Ghada Ismail, Dalia Abdelhamid, Marwa Salah Mostafa, Noha Alaa Eldin Fahim, Ahmed Elshafei, Hossam Abdelghaffar, Nashwa Naguib, Omnia Taher, Menna Asker.
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We conducted a retrospective study in the adult primary immunodeficiency clinic at UAB examining COVID-19 infection and COVID-19 antibody response from vaccination, natural infection, and immunoglobulin replacement from February 2021 to November 2022. Our goal was to determine if nucleocapsid and spike antibodies could be found in our PID patients and if these antibodies could be derived from natural infection, vaccination, or antibody replacement exclusively or combinatory. We hypothesized that increasing antibodies would be detected in our population as the COVID period extended. Two hundred and forty-five subjects were tracked over 336 clinic visits during this period. Our PID population included subjects with CVID, XLA, thymoma, hypogammaglobulinemia, IgA deficiency, IgG subclass deficiency, specific antibody deficiency, Down syndrome, IgM deficiency, and patients with recurrent sinopulmonary infections. We had 196 females and 45 males in our study. In our patient population, 47% of our patient had known COVID-19 infection. Of those 47%, 21% of those infected patients had COVID-19 at least twice. Of those infected, three did not have COVID-19 spike antibodies and chose not to get vaccinated either. Two of those patients were not on IVIG and one was on Pangyza. Of those infected, 70% (n = 80) were on IgG infusions compared to those uninfected, 77% (n = 96) were on IgG infusions. Of interest, we had three XLA patients and all three had COVID-19 infection in the summer 2021. Two of them tested positive for nucleocapsid and spike antibodies in high titers and they were receiving Gammagard or Gamunex infusions, suggesting that these immunoglobulin preparations contain COVID-19 antibodies. We are still in the process of analyzing our data to see if diagnosis, IgG preparations, date of testing, B cell numbers, and drugs play a role in producing nucleocapsid antibodies and high spike antibody titers.Copyright © 2023 Elsevier Inc.
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BackgroundVaccine-induced immunity is very important for controlling the COVID-19 infection. The vaccination supports humoral and cellular immunity, and this is one of the main strategy for us. Various vaccines approved in the countries have been shown to reduce infection rates, severity, and mortality.ObjectivesWe aimed to compare humoral and cellular immune responses after homologous or heterologous vaccination among patients with aiRMDs at their third vaccination with BNT162b2 or with two vaccinations followed by COVID-19 infection. We detected the anti-SARS-CoV2 antibody levels and measured the SARS-CoV-2 reactive B-, or T-cell mediated immunity in aiRMDs receiving homologous (Hom.), heterologous (Het.) vaccines or became infected (Inf.).MethodsA single center observational study evaluated immunogenicity and safety of the third dose vaccines or after two-dose regimen of vaccine and COVID infection in patients with aiRMDs. Neutralizing anti-RBD antibodies and specific T-cell response were measured.ResultsWe showed that following 4 months of the booster vaccination with the third dose of mRNA-based vaccine or after COVID infection, the positive (>21.8 BAU/mL) neutralizing anti-RBD IgG antibody response was outstanding in all three patient groups, 95.5%, 100% and 100% of the homologous and heterologous as well as the SARS-CoV-2 infected groups. Taken together booster vaccinations or SARS-CoV-2 infection after completing 2 doses of the vaccination can lead to the production of neutralizing antibodies still protective in RMD cases after 4 months of the third antigen exposition. The booster vaccination reduces the frequency of hospital admissions and mortality with ai RMDs. The vaccinations are effective independently from the type of vaccine, the SARS-CoV-2 specific memory B-cell populations showed a statistically not significant but lower frequency in the infection group. Clinical activity of aiRMDs was not increased following booster vaccination.ConclusionPatients, who received a heterologous booster vaccine had a higher level of peripheral memory B-cells compared to those who had COVID-19 infection. Biologic therapy decreased the level of B-cells. Patients with a disease duration of more than 10 years had higher level of CD8+TNF-α+ and CD8+IFN-γ+ T-cells compared to patients who were diagnosed less than 10 years ago. The third booster mRNA-based vaccine was as much effective as in the homologous and heterologous patients groups compared who had COVID infection.References[1] Szebeni, G.J.;Gemes, N.;Honfi, D.;Szabo, E.;Neuperger, P.;Balog, J.A.;Nagy, L.I.;Szekanecz, Z.;Puskas, L.G.;Toldi, G.;et al. Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity and in Healthy Controls: A Single Center Study. Front. Immunol. 2022, 13, 846248.[2]Honfi, D.;Gémes, N.;Szabó, E.;Neuperger, P.;Balog, J.Á.;Nagy, L.I.;Toldi, G.;Puskás, L.G.;Szebeni, G.J.;Balog, A. Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients. Int. J. Mol. Sci. 2022, 23, 11411Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundThe COVID-19 pandemic caused concerns whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) and/or prednisolone exhibit an adequate immune response to the applied SARS-CoV2 vaccines.ObjectivesWe established the DECODIR study to assess and compare the efficacy of the SARS-CoV2 vaccines administered as part of the national vaccine roll-out: BNT162b2 vaccine (Pfizer/BioNTech) and mRNA-1273 vaccine (Moderna). The vaccines were offered as two doses four weeks apart;followed by a booster vaccination six months later. This national regimen included inflammatory rheumatic patients regardless of their respective anti-inflammatory treatment. We used patients' SARS-CoV2 IgG serum level as proxy for vaccination response (1).MethodsThe study was conducted as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg, and monitored in the Danish DANBIO registry, were included.Blood samples, Disease activity and treatment information (cs/bDMARD, prednisolone) were collected at baseline (i.e. prior to vaccination), after six weeks, six and twelve months. SARS-CoV-2 IgG levels in serum were assessed by ELISA (Thermo-Fischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as definition of sufficient IgG response. Antibody response was measured and compared at all four time points.Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment (none, cs/bDMARD or prednisolone) and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confidence interval (CI) of the median.ResultsA total of 243 patients were included at baseline and all were followed-up after six weeks;data from 233 patients were available at six months and for 229 patients at twelve months' follow-up. Those 229 patients had completed the national vaccination programme.The measurements performed 6 months after baseline demonstrated a per se decrease of IgG levels for the whole study population (median of 2.08 EliA U/mL at 6 months vs. 16 EliA U/mL at 6 weeks). The final measurements performed after twelve months demonstrated a significant increase of IgG levels. Thus, the completed vaccination programme, was followed by a significant increase in IgG levels (median of 100 EliA U/mL at twelve months vs. 16.5 EliA U/mL at six months, p < 0.001).Sufficient response rates were now recorded in all treatment scenarios, also in patients treated with prednisolone or combination of csDMARD and bDMARD. These two groups were at 6 months characterized by significant lower response rates, when compared with patients without any DMARD treatment.ConclusionCompleted vaccination programme defined as two doses plus booster vaccination resulted in a sufficient vaccination response as measured by IgG levels regardless of RA treatment.It is noteworthy that IgG levels increased markedly in patients treated with a combination of cs/bDMARD or oral prednisolone, who had low IgG levels (below manufacturer's cut-off >=10 EliA U/mL) after 6 months. Our results strongly support the efficacy of the complete vaccination programme including the 3rd booster vaccine in patients with inflammatory rheumatic diseases.Figure 1.Serum IgG-levels at baseline, 6 weeks, 6 months and 12 months;stratified by antirheumatic treatment. (Box plot showing median and interquartile range).[Figure omitted. See PDF]Reference[1]Schreiber K. et al. Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases— an Interim Report from a Danish Prospective Cohort Study. Vaccines 2022, 10(1), 35;https://doi.org/10.3390/vaccines10010035AcknowledgementsWe acknowledge all patients contributing to the DANBIO registry.The Danish Rheumatologic Biobank is a knowledged for handling and storage of biological material.Lab chieftechnician Charlotte Drachmann is acknowledged for her assistance.Disclosure of InterestsChristine Graversgaard: None declared, Karen Schreiber Speakers bureau: Lilly, UCB, Henning Jakobsen: None declared, Randi Petersen: None declared, Anders Bo Bojesen: None declared, Niels Steen Krogh: None declared, Bente Glintborg Grant/research support from: Pfizer, AbbVie, BMS, Sandoz, Merete Lund Hetland: None declared, Oliver Hendricks Speakers bureau: Pfizer, Lilly, Novartis.
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BackgroundComplete peripheral B cell depletion has been considered as a relevant indicator of short-term response to rituximab (RTX) in rheumatoid arthritis (RA) [1,2]. However, no information is available to validate this observation in RA patients long-term treated with RTX.ObjectivesTo determine whether sustained complete B cell (BC) depletion is associated with a better clinical response in RA patients long-term treated with RTX.MethodsRetrospective routine care study conducted in the Rheumatology department of Cochin hospital. We included consecutive patients fulfilling the ACR/EULAR 2010 classification criteria for RA hospitalized in 2021 for a new RTX infusion. All recruited patients had received at least 3 prior RTX infusions and had disease activity assessment (DAS28 and DAS28-CRP) and CD19 counts (Aquios, Beckman Coulter) available during each of the 4 last infusion visits. The primary endpoint was the course of DAS28 and DAS28-CRP, calculated the day of the last 4 infusion visits according to sustained complete (mean CD19 counts <18/µL) or incomplete (mean CD19 counts ≥18/µL) BC depletion. Secondary endpoints were the frequency of end-of-dose effect and patient self-reported RA flares at each infusion visit, as well as the course of pain/fatigue VAS, CRP and gammaglobulin levels according to complete or incomplete B cell depletion.ResultsWe included 126 patients (105 women, 83%) with a mean age of 64±12 years and a mean disease duration of 22± 5 years. Only 43 patients (34%) had maintained complete BC depletion during the last 4 infusions (mean CD19 counts 13±4/µL) (Figure 1A-B). Patients with incomplete BC depletion (n=83, mean CD19 counts: 77±73/µL, p<0.001) did not differ from those who maintained complete BC depletion in terms of age, gender, disease duration, structural damages and concomitant treatment.Patients with incomplete BC depletion had a higher frequency of rheumatoid factor (92% vs. 77%, p=0.018) and ACPA (84% vs. 72%, p=0.11);these patients had received RTX for a longer period (99±57 months vs. 69±47 months, p=0.003), with significantly higher number of infusions (14±7 vs. 12±6 infusions, p=0.037) and increased cumulative dose (10±6 g vs. 8±5 g, p=0.10) compared to patients with sustained complete BC depletion. On the other hand, their interval between 2 infusions was significantly longer (8±3 months vs. 6±1 months, p<0.001).The course of DAS28 and DAS28-CRP during the last 4 infusions was not different between the 2 groups (Figures 1C-D). The mean DAS28 and DAS28-CRP calculated at the time of last 4 infusion visits did not differ between patients with incomplete or sustained complete BC depletion (DAS28: 2.71±1.06 vs. 3.01±1.10, p=0.33 and DAS28-CRP: 2.53±0.88 vs. 2.88±0.84, p=0.095). The frequency of an end-of-dose effect and self-reported flares was similar between the 2 groups, as well as the evaluation of pain VAS, asthenia VAS, CRP and gammaglobulin levels (Figures 1E-H).ConclusionMaintaining complete BC depletion is not a therapeutic target to achieve in RA patients in long-term maintenance therapy with RTX. These results show that it is possible to space out RTX infusions to 8 months without loss of clinical benefit, which remains identical to that of patients treated every 6 months with sustained BC depletion. This result may have clinical implications during the COVID-19 pandemic since the antibody response to SARS-CoV-2 vaccination is preferentially obtained in patients with detectable B cells [3].References[1]Vital EM et al. Arthritis Rheum 2011;63:603–8.[2]Dass S et al. Arthritis Rheum 2008;58(10):2993–2999.[3]Avouac et al, Rheumatology 2022Figure 1.Course of mean (±SD) CD19, DAS28, DAS28-CRP, pain and fatigue VAS, CRP and gammaglobulins at the last 4 RTX infusion visits according to sustained complete or incomplete B cell depletion (CBCD and IBCD respectively).[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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BackgroundData on serological immunity after three doses and the long-term immunogenicity (persistence) of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with different immunomodulating drugs are still limited.ObjectivesTo elucidate if 1) a third dose COVID-19 vaccine improves antibody responses, compared to two doses, in patients with IRD treated with biologic or targeted synthetic DMARD (b/tsDMARDs) treatment given as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) compared to controls, and 2) the persistence of antibody response after two doses of COVID-19 vaccine in IRD patients.MethodsAntibody levels to two antigens representing Spike full length protein and Spike S1 and a Nucleocapsid C-terminal fragment (used to confirm previous COVID-19 infection) were measured in serum samples collected 2-12 and 21-40 weeks after the second vaccine dose and 2-12 weeks after the third dose using a multiplex bead-based serology assay. A sufficient antibody response (seropositivity) was defined as having antibodies over the cut-off level for both spike antigens (1). WT (wild type) anti-Spike IgG and omicron BA.1 and BA.2 variants were measured. Patients with IRD receiving immunomodulating treatment, regularly followed at a rheumatology department and a group of controls were recruited from five Swedish region.ResultsIn total, 323 of 414 patients with IRD and 36 controls who received three vaccine doses participated in this part of the study. Following treatment groups were included: rituximab (n=118;68% female;mean age 67 years), abatacept (n=18;72% female;mean age 64 years), IL6r inhibitors (n=60;73% female;mean age 64 years), JAK-inhibitors (n=44;80% female, mean age 52 years), TNF-inhibitors (n=59;70% female;mean age 47 years;), IL12/23/17 inhibitors (n=24;46% female;mean age 54 years) and controls (n=36;75% female, mean age 51 years). b/ts DMARD treatment was given as monotherapy or in combination with csDMARD, methotrexate (MTX) being the most frequently used csDMARD (32.5%). Compared to results after two vaccine doses, proportion (%) of seropositivity after three vaccine doses increased significantly in groups rituximab +/- DMARD (p=0.003 and p=0.004, respectively), IL6r inhibitors +DMARD (p=0.02), and abatacept+DMARD (p=0.01). However, the proportion of seropositivity after three vaccine doses was still significantly lower in rituximab treated patients (52%) compared to other treatment groups or controls (p<0.001) (Figure 1A/B). Antibody response to WT, omicron sBA.1 and sBA.2 showed similar pattern with the lowest levels among patients treated with rituximab.When antibody response was compared between 2-12 weeks and 21-40 weeks after second dose, the proportion of seropositive rituximab treated patients decreased from 34.9 % to 32.6%. All patients with JAK inhibitors and with JAK-inhibitors and IL6r-inhibitors seropositive 21-40 weeks after the second vaccine dose. Patients treated with other bDMARDs were not included in this analysis due to limited number participants.ConclusionIn this Swedish study including IRD patients receiving different b/t DMARDs, a sufficient immunogenicity of the third dose of COVID-19 vaccine was observed in all treatments with exception for rituximab. However, the increased proportion of seropositivity after the third COVID-19 vaccine doses in rituximab and other patients with insufficient response to two doses including response to the omicron variants, supports the current recommendations on additional booster doses. The immunogenicity of two vaccine doses was preserved to 40 weeks in majority of patients treated with different immunomodulating treatment with exception for rituximab.Figure 1.AcknowledgementsThe study has been supported by the independent research grants from Roche.Disclosure of InterestsMartina Frodlund: None declared, Per Nived: None declared, Katerina Chatzidionysiou Consultant of: consultancy fees from Eli Lilly, AbbVie and Pfizer., Grant/research support from: Research grand from Galapagos, Anna ödergren: None declared, Eva Klingberg: None declared, Monika Hansson: None declared, Elisa Pin: None declared, Lars Klareskog: None declared, Meliha C Kapetanovic Grant/research support from: independent research grants från Pfizer and Roche.
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Antibody production in response to infection or vaccination is a crucial process to combat and prevent infectious diseases. Regarding SARS-CoV-2, different features have been observed and literature still lacks consensus about it. Here, we discuss the production of antibodies during SARS-CoV-2 infection and its therapeutic relevance. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Worldwide, infectious diseases have contributed significantly to morbidity and mortality;among the leading causes of death are pneumonia, respiratory infections and Covid-19. Stem cell therapy will be used to treat virus-infected patients in an effective and safe manner. A cross-sectional questionnaire was used to collect data from doctors. Most doctors are aware of the applications of stem cells, but they do not confirm their usage because clinical trials are ongoing. Instead, they show support for using stem cells to treat patients. Stem cells have been hoping to help repair damaged tissues in the respiratory system to promote faster recovery. Stem Cells are being studied in current clinical trials for their efficacy and safety in virus severe pneumonia and respiratory infections. The doctors suggested that stem cells have been used in infectious diseases to improve their health.Copyright © 2023 Health Biotechnology And Biopharma. All rights reserved.
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BackgroundTreatment with Rituximab (RTX) in patients with rheumatic diseases (RD) has presented a challenge during the COVID-19 pandemic, as RTX leads to markedly reduced and often undetectable antibody responses after COVID-19 vaccination (1).ObjectivesTo investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with RD who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion.MethodsFrom a RD cohort (COPANARD) vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies (abs) and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralizing abs, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. This study was funded by the Danish Rheumatism Association.ResultsPatient demographics are given in Table 1. Forty-seven percent of cases had detectable total SARS-CoV-2 abs and neutralizing abs after revaccination. However, antibody levels were significantly lower than in controls and blood donors (p<0.008), Figure 1A+B. Revaccination induced an antibody class switch in cases with a decrease in detectable IgM abs (Baseline 11/17, Followup 3/17) and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups, Figure 1C. The proportion of cases with detectable CD4+ T cells increased from 69% to 88% (p=0.25), and for CD8+ T cells, the proportion decreased from 88% to 82% (p=1.00). Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors, Figure 1D. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination, Figure 1D.Univariate logistic regression analysis was performed to analyze if active RTX treatment, the presence of B-cells, or a positive T-cell response prior to revaccination predicted seroconversion of total SARS-CoV-2-abs in the patient cohort. We did not find a significant explanatory effect of either variable in the univariate logistic models, data not shown.Table 1.DemographicsCases Revaccination, n=17Controls Boost, n=29Female sex, no(%)1482%2172%Age, median (IQR)6549 - 706762 - 72Disease duration, years1510 - 18229 - 31Rheumatoid Arthritis/SLE13/410/19None DMARD529%828%Prednisone424%13%Methotrexate741%1241%Hydroxychloroquine212%414%None biologic treatment424%931%Rituximab1271%0TNF-inhibitors16%724%JAK-inhibitors0621%IL-6-inhibitors, Abatacept, Benlysta0724%Previous rituximab treatmentAny rituximab treatment1694%13%RTX within the last 15 months, no1488%0Cumulative total dose, mg134-242Time from RTX to revaccination, months95-1249Figure 1.ConclusionIn conclusion, forty-seven percent of initial non-responders were able to seroconvert after two-dose revaccination. However, plasma concentrations of the antibodies against SARS-COV-2 and the levels of neutralizing capacity remained significantly lower than in immunocompetent blood donors. B-cell levels or T-cell responses before revaccination did not predict seroconversion. Our study suggests that patients with RDs who did not mount a detectable serological response to a COVID-19 mRNA vaccine have a T cell response similar to immunocompetent controls. Future studies should establish the antibody levels that identify RD patients without sufficient protection against SARS-CoV-2 infection.References[1]Troldborg A, et al. Time Since Rituximab Treatment Is Essential for Developing a Humoral Response to COVID-19 mRNA Vaccines in Patients With Rheumatic Diseases. J Rheumatol. 2022.AcknowledgementsThe Danish Rheumatism Association [grant number R203-A7217]. We acknowledge all patients and blood donors contributing to the stud for their invaluable participation. The authors would like to thank Sif Kaas Nielsen and Mads Engelhardt Knudsen, the Laboratory of Molecular Medicine at Rigshospitalet, for their excellent technical assistance in analyzing the samples.Disclosure of InterestsNone Declared.
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Aims/Hypothesis: Covid-19 has been associated with poorer outcomes in individuals with type 1 diabetes. Most existing data relate to hospitalised patients with few data available on seroprevalence and the effects of Covid-19 on people with diabetes in the general population. We examined antibody responses to SARS Cov-2 infection and vaccination in people with and without diabetes. Method(s): From June 2020, capillary blood samples collected remotely from 1828 individuals (type 1 diabetes n = 267) were analysed for SARS-CoV- 2 antibodies to RBD (infection pre-Jan 2021/vaccination post -Jan 21) and N (infection post Jan 21) antigens using low serum volume luciferase-based assays developed "in house". Questionnaire data recording experiences of Covid-19 and vaccinations dates were collected simultaneously with the samples. Median antibody levels were compared using Kruskal-Wallis tests. Result(s): There was evidence of SARS CoV-2 infection in 317/1828 (17%) of individuals screened with no evidence of more severe self-reported Covid-19 symptoms in those with diabetes (no participants were hospitalised) and almost a quarter of those with type 1 diabetes were asymptomatic. Although samples were collected at variable time points from vaccination, robust antibody responses to vaccination were observed (Pfizer, AstraZeneca, and Moderna) after the second vaccination with no differences in antibody levels between those with and without diabetes (p = 0.3). Conclusion(s): Hospitalised individuals with Covid-19 and type 1 diabetes were at greater risk of complications but this study shows that among the non-hospitalised population, clinical symptoms, antibody responses to infection, and vaccination in those with type 1 diabetes was similar to control subjects.
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This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2-4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4-6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.
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COVID-19 , Multiple Sclerosis , Humans , COVID-19 Vaccines , T-Lymphocytes , COVID-19/prevention & control , Multiple Sclerosis/drug therapy , SARS-CoV-2 , RNA, Messenger , Immunity , mRNA Vaccines , Immunoglobulin G , Antibodies, Viral , VaccinationABSTRACT
BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.
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COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , Antibody Formation , SARS-CoV-2 , RNA, Messenger , mRNA Vaccines , Antibodies, ViralABSTRACT
Patients with chronic liver disease (CLD) are at a greater risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. This study investigated the antibody response to inactivated SARS-CoV-2 vaccination in a long-term prospective cohort of CLD patients. The seropositivity rates and antibody concentrations of anti-SARS-CoV-2 NAbs were similar among patients with different severity of CLD 6 months after the third vaccination. In addition, older CLD patients appeared to have lower antibody responses. These data might be helpful to inform vaccine decisions for patients with chronic liver disease.