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OBJECTIVES: Although reduced cognitive function has been demonstrated after liver transplantation in children, few data are available concerning motor competence. METHODS: Thirty-five children ages 4 to 12 years were tested using Movement Assessment Battery for Children (M-ABC) test at a median of 5.1 (3.9-6.9) years after liver transplantation and compared with reference material of healthy children. RESULTS: Children with transplantation had worse M-ABC score 8.0 (interquartile range 5.0-11.5), compared with healthy children 3.5 (1.0-6.0) (P < 0.0001). All of the subscores (manual dexterity [P < 0.0001], ball skills [P = 0.0037], and balance [P = 0.0032]) were significantly worse in the children with liver transplantation compared with the healthy reference group. Twenty-nine percent of the children with liver transplantation had impaired motor competence, compared with 9% of a healthy reference group. Seventeen of the patients with transplantation were retested 1 year later, and 11 were tested 4 years later with no changes in total M-ABC score. Ball skill competence was worse 4 years after first assessment (P = 0.013). For children with transplantation and cholestatic liver disease (n =26), renal function was a significant predictor for total M-ABC score (P = 0.018). CONCLUSIONS: Children with liver transplantation had impaired motor competence compared with healthy children. Ball skills developed adversely several years after liver transplantation, and motor competence did not improve with time after transplantation. Renal function was a significant predictor for motor competence in children with liver transplantation and cholestatic liver disease.
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Transplante de Fígado/efeitos adversos , Transplante de Fígado/reabilitação , Destreza Motora/fisiologia , Movimento/fisiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Fatores de Tempo , Transplantados/estatística & dados numéricos , Resultado do TratamentoRESUMO
OBJECTIVES: To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. METHODS: IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2-5 weeks post-immunisation. RESULTS: Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). CONCLUSION: Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. TRIAL REGISTRATION NUMBER: NCT04798625.
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COVID-19 , Glicoproteína da Espícula de Coronavírus , Vacinas , Humanos , Incidência , Vacinas contra COVID-19/uso terapêutico , Estudos Prospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Imunização , Terapia de Imunossupressão , Agentes de Imunomodulação , Imunidade AdaptativaRESUMO
Background: Data on response and safety of repeated vaccinations and hybrid immunity in patients with immune-mediated inflammatory diseases on immunosuppressive therapy is needed to further develop vaccination strategies in this vulnerable population. This study aimed to evaluate hybrid immunity and humoral immune response and safety of four SARS-CoV-2 vaccine doses in patients with immune-mediated inflammatory diseases on immunosuppressive therapy. Methods: This prospective observational Norwegian study of vaccine response to COVID-19 (Nor-vaC) included adult patients aged 18 years and older with immune-mediated inflammatory diseases (rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis) on immunosuppressive therapy, who had received four SARS-CoV-2 vaccine doses (vaccine group) or three vaccine doses followed by COVID-19 (hybrid group), and healthy controls receiving three vaccine doses (control group). Patients were recruited from the Division of Rheumatology at Diakonhjemmet Hospital, Oslo, and the Department of Gastroenterology at Akershus University Hospital, Lørenskog. Patients who had COVID-19 before the third vaccine dose, and patients with allergies or intolerances to elements of the vaccine were excluded. Antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD antibodies) were assessed 2-4 weeks following vaccination or COVID-19. This study is registered at Clinialtrials.gov, NCT04798625. Findings: Between Nov 12, 2021, and April 19, 2022, 1458 participants with immune-mediated inflammatory diseases provided post-vaccination samples at 2-4 weeks following a third vaccine dose. After 544 participants were excluded, 715 (78%) of the remaining 914 participants received the fourth dose of the vaccine, and of these, 536 (75%) provided post-vaccination samples 2-4 weeks after their fourth vaccination (vaccine group). 199 (22%) of the 914 had COVID-19 after their third dose of the vaccine and of these, 167 (84%) provided samples (hybrid group). 256 of the eligible 703 patients had rheumatoid arthritis, 107 had spondyloarthritis, 115 had psoriatic arthritis, 130 had Crohn's disease, and 95 had ulcerative colitis). Median age was 56 years [IQR 45-65], 398 (57%) were women, and 305 (43%) were men. Patients in the vaccine group had higher anti-RBD antibody concentrations following the fourth vaccine dose (median 6192 BAU/ml [IQR 2878-11 243]) than after the third dose (median 5087 BAU/ml [1250-9081]; p< 0·0001), but lower antibody concentrations than the control group following the third dose (median 7595 BAU/ml [5916-12 001]; p< 0·0001). Antibody concentrations were higher in the patients in the hybrid group (23 548 BAU/ml [IQR 11 440-35 935]) than in the vaccine group (p<0·0001). No difference was found in antibody concentrations between the fourth dose of BNT162b2 (full-dose) and mRNA-1273 (half-dose). Patients and controls had a comparable safety profile after both three and four vaccine doses. Interpretation: Vaccine boosters improve humoral immune responses and are safe in patients with immune-mediated inflammatory diseases on immunosuppressive therapy, and administration should be considered regularly in this patient group. Hybrid immunity with omicron induces a strong humoral response suggesting longer intervals between booster doses in this patient group. Funding: The South-Eastern Norway Regional Health Authority, The Coalition for Epidemic Preparedness Innovations, Akershus University Hospital.
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BACKGROUND: In rituximab-treated patients with rheumatoid arthritis, humoral and cellular immune responses after two or three doses of SARS-CoV-2 vaccines are not well characterised. We aimed to address this knowledge gap. METHODS: This prospective, cohort study (Nor-vaC) was done at two hospitals in Norway. For this sub-study, we enrolled patients with rheumatoid arthritis on rituximab treatment and healthy controls who received SARS-CoV-2 vaccines according to the Norwegian national vaccination programme. Patients with insufficient serological responses to two doses (antibody to the receptor-binding domain [RBD] of the SARS-CoV-2 spike protein concentration <100 arbitrary units [AU]/mL) were allotted a third vaccine dose. Antibodies to the RBD of the SARS-CoV-2 spike protein were measured in serum 2-4 weeks after the second and third doses. Vaccine-elicited T-cell responses were assessed in vitro using blood samples taken before and 7-10 days after the second dose and 3 weeks after the third dose from a subset of patients by stimulating cryopreserved peripheral blood mononuclear cells with spike protein peptides. The main outcomes were the proportions of participants with serological responses (anti-RBD antibody concentrations of ≥70 AU/mL) and T-cell responses to spike peptides following two and three doses of SARS-CoV-2 vaccines. The study is registered at ClinicalTrials.gov, NCT04798625, and is ongoing. FINDINGS: Between Feb 9, 2021, and May 27, 2021, 90 patients were enrolled, 87 of whom donated serum and were included in our analyses (69 [79·3%] women and 18 [20·7%] men). 1114 healthy controls were included (854 [76·7%] women and 260 [23·3%] men). 49 patients were allotted a third vaccine dose. 19 (21·8%) of 87 patients, compared with 1096 (98·4%) of 1114 healthy controls, had a serological response after two doses (p<0·0001). Time since last rituximab infusion (median 267 days [IQR 222-324] in responders vs 107 days [80-152] in non-responders) and vaccine type (mRNA-1273 vs BNT162b2) were significantly associated with serological response (adjusting for age and sex). After two doses, 10 (53%) of 19 patients had CD4+ T-cell responses and 14 (74%) had CD8+ T-cell responses. A third vaccine dose induced serological responses in eight (16·3%) of 49 patients, but induced CD4+ and CD8+ T-cell responses in all patients assessed (n=12), including responses to the SARS-CoV-2 delta variant (B.1.617.2). Adverse events were reported in 32 (48%) of 67 patients and in 191 (78%) of 244 healthy controls after two doses, with the frequency not increasing after the third dose. There were no serious adverse events or deaths. INTERPRETATION: This study provides important insight into the divergent humoral and cellular responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis. A third vaccine dose given 6-9 months after a rituximab infusion might not induce a serological response, but could be considered to boost the cellular immune response. FUNDING: The Coalition for Epidemic Preparedness Innovations, Research Council of Norway Covid, the KG Jebsen Foundation, Oslo University Hospital, the University of Oslo, the South-Eastern Norway Regional Health Authority, Dr Trygve Gythfeldt og frues forskningsfond, the Karin Fossum Foundation, and the Research Foundation at Diakonhjemmet Hospital.
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OBJECTIVE: Immunogenicity and safety following receipt of the standard SARS-CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS-CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. METHODS: Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS-CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were performed prior to and 2-4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS-Cov-2 spike protein, were allotted a third vaccine dose. RESULTS: A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192-4,191) than in controls (median 3,355 AU/ml [IQR 896-7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA-1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. CONCLUSION: IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.
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Vacinas contra COVID-19 , COVID-19 , Vacinas Virais , Adulto , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunogenicidade da Vacina , Terapia de Imunossupressão , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Vacinas Virais/efeitos adversosRESUMO
OBJECTIVE: To compare the 6-minute walking distance (6MWD) in a population-based cohort of patients with osteoarthritis (OA) with that in matched peers from the general population, and to explore the associations between walking ability and risk of cardiovascular disease (CVD) in the OA cohort. METHODS: This cross-sectional study included individuals (ages 40-80 years) who had self-reported OA (n = 500) in a previous population-based study and age- and sex-matched peers from the general population (n = 235). Clinical examinations of the patients with OA included classification according to the American College of Rheumatology criteria, blood sampling, and measuring arterial stiffness (PWV; pulse wave velocity). Group differences in the 6MWD were calculated with t-tests. The association between walking ability and CVD risk in the OA cohort was examined using multivariate regression models. RESULTS: In the age-stratified analyses, the largest mean difference in the 6MWD was observed in the youngest age groups (40-49 years); female patients in the OA group walked 84.6 fewer meters compared with the reference group (579.4 meters and 663.9 meters, respectively; P < 0.001), and male patients walked 88.3 fewer meters compared with the reference group (619.9 meters and 708.3 meters, respectively; P = 0.001). In the OA group, the 6MWD was significantly associated with PWV in the adjusted analysis (P = 0.001); an increase in the walking distance of 100 meters corresponded to a reduction in PWV of 0.3 meters/second. CONCLUSION: Even at age 40 years, patients with OA had a significantly shorter mean walking distance compared with their matched peers, underlining the importance of an early clinical approach to OA. Furthermore, in the OA group, the 6MWD was significantly associated with arterial stiffness, suggesting that walking ability is important for the CVD risk profile in patients with OA.