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Specific immunotherapy (SIT) is the first-choice treatment for allergic respiratory diseases. Over the years, the literature has demonstrated that the focus of specific allergen immunotherapy has always been on the search for a safe, easy to use treatment to ensure good patient compliance. The COVID-19 pandemic has severely put many treatment plans to the test but, in the immunotherapy sector, it has been and is still possible to adopt safe treatments that allow them to be continued even during the course of emergency vaccinations, like that of COVID-19. © 2022 TeknoScienze. All rights reserved.
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Aim/Introduction: In SARS-CoV2 outbreak scenario, many considerations about possible long-term effects of this infection can be made. Early evidences reported in literature about the relation between long-COVID disease and brain involvement in patients with persistent neurological symptoms, found brain hypometabolism on 18F-FDG PET/CT. Our study aims to evaluate the impact of SARSCoV2 infection on brain metabolism in a long-term setting, also in asymptomatic patients. Material(s) and Method(s): Brain PET scans of 48 patients with documented previous SARS-CoV2 infection (COVID-group), performed from January to December 2021, were analysed and compared with brain PET scans of 48 patients, controlled for age and sex, who didn't experience the infection (control-group) using a quantitative software-aided approach. Patients with documented brain metastases or neurodegenerative diseases were excluded. No patient had neurological symptoms at the time of PET. CortexID Suite software (GE Healthcare) was applied for a segmentation analysis reporting Z score (ZS) values for each brain area in both groups. Basing on hypometabolism severity, the sample was divided as follows: normal (>=-1 ZS), mild (between -1 and -2 ZS), severe (<=-2 ZS). For COVID-group, time intercurred from infection to PET was recorded. Differences between ZS per areas between the two groups were evaluated using Mann-Withney-U test. Considering hypometabolism severity, Chi-Square test was applied to evaluate differences between groups. Finally, Pearson's test was used to correlate COVID-group ZS and time intercurred from infection. Result(s): Mean age of patients was 63.2 and 63.6 years old in the COVID-and control-group respectively. In both groups, 22/48 were male. In COVID-group 27/48 patients have had symptoms (cough, fever, dyspnoea) during SARS-CoV2 infection. The majority of brain areas showed a statistically significant difference in ZS values between groups. According to hypometabolism severity, left pre-frontal medial (p=0.032), right sensory-motor (p=0.014), right inferior parietal (p=0.001) and right lateral temporal (p=0.002) areas showed a statistically significant difference between COVIDand control-group with a prevalence in COVID-group of mild and severe brain hypometabolism. Lower ZS values were observed in patients with a longer time intercurred from infection to PET/CT scan. Conclusion(s): Our preliminary results confirm the impact of SARS-CoV2 infection on brain metabolism, consisting mostly in a mild hypometabolism. The presence of this metabolic pattern in patients without neurological symptoms suggests a devious action of the infection. Further studies, also using serial PET, are necessary to explore whether these metabolic alterations are transient or predictive of a future clinical manifestation.
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Background: Immunosuppressive therapies may impact immune response to COVID-19 vaccines in persons with multiple sclerosis (pwMS). Accordingly, effects of vaccination in pwMS treated with disease-modifying therapies (DMTs) need further elucidation. Aim(s): To investigate COVID-19 BNT162b2 vaccine effect concerning antibody seroconversion, T cells-associated cytokines production and immunophenotype assessment in pwMS under three different DMTs: cladribine, fingolimod, ocrelizumab. Method(s): Enzyme immunoassay test was used for anti-spike IgG detection in 98 DMTs-treated pwMS completing first vaccination cycle. In a subset of patients (n=47), serum T cells-associated cytokines (GrB, IFN-gamma and TNF-alpha) were quantified using an automatic ELISA (ELLA) and blood immunophenotype was assessed by flow cytometry. ANCOVA followed by post hoc tukey's test was used to compare anti-spike IgG response in the different DMTs, Student's paired t-test was used to evaluate differences between pre- and post-vaccination in pairwise samples and Pearson's correlation was applied to evaluate association between spike-specific IgG antibody titer and lymphocytes count. Result(s): More pwMS treated with ocrelizumab (63%) lacked anti-spike IgG compared to patients treated with cladribine (14%) and fingolimod (20%) (p<0.001). When present, the anti-spike IgG titer in the ocrelizumab group was lower than in cladribine- (p<0.001) and in fingolimod-treated pwMS (p=0.003). No significant differences in lymphocytes count and T-cell associated cytokines were observed in cladribine- and in fingolimod-treated pwMS, while in pwMS on ocrelizumab a significant increase in GrB serum levels (p=0.021) and a trend of increased CD4+ T cells count were observed after vaccination. Specifically considering non-seroconverted ocrelizumab-treated pwMS, a significant increase of GrB serum levels (p=0.008) and of CD4+ T lymphocytes count (p=0.040) was foundafter vaccination and a negative correlation was observed between anti-spike IgG production and CD4+T cells count (rho=-0.452, p=0.014). Conclusion(s): Our data confirmed differences in spike-specific antibodies among different DMTs and provided evidence of T-cell immunity preservation and activations after BNT162b2 vaccination in ocrelizumab-treated pwMS, specifically in pwMS patients lacking anti-spike IgG, suggesting a protective T-cell response that might explain why the ongoing treatment with ocrelizumab is not associated with a higher risk of COVID-19 infection.
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Background Inflammatory Bowel Disease(IBD) and Irritable Bowel Syndrome(IBS) are gastrointestinal disorders which differ in pathophysiology and management. The use of immunomodulatory drugs brings concerns which increased during the pandemic. Similarly, patients with IBS may have concerns about the effect of infection and vaccine on their wellbeing. The aim of this study was to assess for any differences in swabbing, vaccine uptake, COVID-19 infection, hospitalisation rates and outcomes in patients with IBD on immunomodulatory treatment and patients with IBS. Methods Patients were recruited through the local database (March, 2020 – August, 2021). All IBD patients had a histological diagnosis while IBS patients were diagnosed according to ROME IV criteria. All patients were offered vaccination. Apart from demographic data the following was collected: number of COVID-19 swabs taken, vaccination rates, type of vaccine administered, infection secondary to COVID-19, hospitalization and outcomes. Results Overall, 250 IBD patients (43.6% female) and, 250 patients with IBS (78.4% female) were recruited. The mean patient age in the IBS cohort was, 40.6 years (SD ±, 11.99) whilst the mean patient age in the IBD cohort was, 40.7 years (SD±15.7). Patients with IBD underwent significantly more COVID-19 swab tests (n=759) than patients with IBS (n=615) (p =0.02). Patients with IBD were having the following biological therapy:, 62.8% Infliximab, 24.8% Adalimumab, 10% Vedolizumab and, 2.4% Ustekinumab. There was no significant difference in COVID-19 infection rate between the IBS cohort (8.8%;n=22 patients;, 2 patients not vaccinated) and the IBD cohort (6.4%;n=16 patients;, 3 patients not vaccinated)(p=0.3). The vaccine uptake rate was similar (IBD:, 91.2%, IBS: 90%). Table, 1 demonstrates the type of vaccine administered to both cohorts. In the IBS cohort, 1 patient was admitted to hospital in view of symptomatic hypoxaemia. The patient was treated with oxygen and dexamethasone, but did not require ventilatory support. Within the IBD cohort, 3 patients requiring admission for IBD related treatment, tested positive asymptomatically on pre-admission COVID-19 screening. All had an uneventful outcome.Table 1CohortPfizerAstraZenecaJohnson&JohnsonModernaIBD43%54%1%2%IBS57%31%7%5% Conclusion This study demonstrates that vaccine uptake, Covid-19 infection rates and outcomes were similar in patients with IBS and IBD patients on immunosuppressive therapy. However, IBD patients underwent significantly more swabbing than patients with IBS and this was generally due to patient concern of acquiring Covid-19 while being on immunosuppresive medications. This added psychological burden may further impact patients’ psychological state and thus their quality of life.
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Introduction: Pivotal anti-SARS-CoV-2 vaccines clinical trials did not include patients with immune-mediated conditions such as inflammatory bowel disease (IBD). We aimed to describe the implementation of anti-SARS-CoV-2 vaccines among IBD patients, patients' concerns before vaccination and side-effect profile of the anti-SARS-CoV-2 vaccines using real-world data. Methods: An anonymous web-based self-completed survey was distributed in 36 European countries between June and July 2021. The results of patients' characteristics, concerns, vaccination status and side-effect profile were analysed using descriptive statistics and logistic regression. Results: Among the 3272 IBD patients completing the survey (0.1% of the IBD European population), 79.6% had received at least one dose of anti-SARS-CoV- 2 vaccine, and 71.7% had completed the vaccination process. Most of the patients (70.6%) were vaccinated with the Pfizer-BioNTech (BNT162b2) vaccine. Patients over 60 years old had a significantly higher rate of vaccination (OR 2.98, 95% CI 2.20-4.03, p<0.001). Patients' main concerns before vaccination were the possibility of having worse vaccine-related adverse events due to their IBD (24.6%), having an IBD flare after vaccination (21.1%) and reduced vaccine efficacy due to IBD or associated immunosuppression (17.6%). After the first dose of the vaccine, 72.4% had local symptoms at the injection site and 51.4% had systemic symptoms (5 patients had non-specified thrombosis). Adverse events were less frequent after the second dose of the vaccine and in older patients. When comparing with previous studies from the general population, the IBD patients answering the survey did not seem to have increased side effects (table 1). Only a minority of the patients were hospitalized (0.3%), needed a consultation (3.6%) or had to change IBD therapy (13.4%) after anti- SARS-CoV-2 vaccination. Conclusion: Although IBD patients raised concerns about the safety and efficacy of anti-SARS-CoV-2 vaccines, the implementation of vaccination in those responding to our survey was high and the adverse events were comparable to the general population, with minimal impact on their IBD. (Table Presented)
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In order to fight the SARS-CoV-2 pandemic, mass-vaccination programs have been launched globally starting December 2020. The pace of COVID-19 vaccines development was impressive and although data from clinical trials and post-authorization studies showed acceptable safety profile, additional studies and long-term population-level surveillance are needed. A possible link between all type of vaccination and immunological diseases is perhaps one of the hottest topics in literature;correspondingly, there is growing concern over the small but growing number of case reports linking COVID-19 vaccines with the development of glomerular disease. Our group conducted a systematic review of such cases. Results showed that IgA nephropathy (IgAN) and Minimal Change Disease (MCD) are the most frequently associated glomerulopathies. Interestingly, IgAN cases are mostly flares occurring few hours after the second dose of RNA vaccines and have a good clinical outcome, while both de novo and recurring MCD can occur up to 28 days after the first or second dose of vaccines. RNA vaccines are the most common vaccine type to be associated with glomerulopathy. Of course, this may simply reflect the more widespread use of these vaccines. However, compared to traditional vaccines, they do seem produce a higher antibody response and a stronger CD8+ T- and CD4+ T-cell response, including higher production of chemokines and cytokines.
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Introduction: More than 2.5 million people in Europe are diagnosed with inflammatory bowel diseases (IBD). IBD affects the quality of life, but also has important consequences for health systems. It remains unknown if variations in IBD care and education differs across Europe and to help address this question, we conducted this European Variation In IBD PracticE suRvey (VIPER) to study potential differences. Aims & Methods: This trainee-initiated survey, run through SurveyMonkey ®, consisted of 47 questions inquiring basic demographics, IBD training and clinical care. The survey was distributed through social media and national GI societies from December 2020 - January 2021. Results were compared according to GDP per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). Differences between groups were calculated using the chi2 statistic. Results: The online survey was completed by 1268 participants from 39 European countries. Most of the participants are specialists (65.3 %), followed by fellows in training (>/< 3 years, 19.1%, 15.6 %). Majority of the responders are working in academic institutions (50.4 %), others in public/ district hospitals (33.3 %) or private practices (16.3 %). Despite significant differences in access to IBD-specific training between high (56.4%) and low (38.5%) GDP countries (p<0.001), majority of clinicians feels comfortable in treating IBD (77.2% vs 72.0%, p=0.04). GDP was not a factor that dictated confidence in treating patients. IBD patients seen per week, IBD boards and especially IBD specific training were factors increasing confidence in managing IBD patients. Interestingly, a difference in availability of dedicated IBD units could be observed (58.5% vs 39.7%, p<0.001), as well as an inequality in multidisciplinary meetings (72.6% vs 40.2%, p<0.001), which often take place on a weekly basis (53.0%). In high GDP countries, IBD nurses are more common (86.2%) than in low GDP countries (36.0%, p<0.001), which is mirrored by differences in nurse-led IBD clinics (40.6% vs 13.8%, p<0.001). IBD dieticians (32.4% vs 16.6%) and psychologists (16.7% vs 7.5%) are mainly present in high GDP countries (p<0.001). In the current COVID era, telemedicine is available in 58.4% vs 21.4% of the high/low GDP countries respectively (p<0.001), as well as urgent flare clinics (58.6% vs 38.7%, p<0.001) and endoscopy within 24 hours if needed (83.0% vs 86.7% p=0.1). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. Almost all (94.7%) use faecal calprotectin for routine monitoring, whereas half also use intestinal ultrasound (47.9%). Conclusion: A lot of variability in IBD practice exists across Europe, with marked differences between high vs low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardise IBD care across Europe.
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BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.
Subject(s)
Anosmia/etiology , COVID-19/complications , Headache/etiology , Myalgia/etiology , Psychomotor Agitation/etiology , Europe , Health Surveys , Humans , NeurologyABSTRACT
BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.
Subject(s)
COVID-19 , Nervous System Diseases/therapy , Pandemics , Patient Care Management , Consensus , Delphi Technique , Guidelines as Topic , Humans , NeurologyABSTRACT
The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.