ABSTRACT
BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: ⢠SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. ⢠Infection of endocrine organs induces interferon response. ⢠Interferon response is observed in adipose tissue independently of virus presence. ⢠Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. ⢠Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.
ABSTRACT
This issue contains 13 articles on the use of virtual anatomy, histology and embryology in research and education;digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications;an international collaborative approach to learning histology using a virtual microscope;delivery anatomy kits to help keep practical veterinary classes during the COVID-19 pandemic;how virtual animal anatomy facilitated a successful transition to online instruction and supported student learning during the coronavirus pandemic;using videos in active learning in veterinary anatomy;dissection videos as a virtual veterinary anatomy peer learning tool at the University of Tehran during the COVID-19 pandemic;a new virtual platform for teaching comparative animal neuroanatomy based on metameric slices of the central nervous system;application of student remote and distance research in neuroanatomy by mapping Dscaml1 expression with a LacZ gene trap in mouse brain;implementing a multi-colour genetic marker analysis technique for embryology education;impact of COVID-19 on student attainment and pedagogical needs when undertaking independent scientific research;extended reality veterinary medicine case studies for diagnostic veterinary imaging instruction and assessing student perceptions and examination performance and students' performance in teaching neuroanatomy using traditional and technology-based methods. 16 proceedings from the Trans-European Pedagogic Anatomy Research Group (TEPARG) Hybrid Meeting entitled "Hybrid Anatomy Education: Barriers and Enablers for Students and Educators" held in Barcelona, Spain, during 5 March 2022, are also included.
ABSTRACT
SARS-CoV-2-mediated interactions with drug metabolizing enzymes and membrane transporters (DMETs) in different tissues, especially lung, the main affected organ may limit the clinical efficacy and safety profile of promising COVID-19 drugs. Herein, we investigated whether SARS-CoV-2 infection could dysregulate the expression of 25 clinically relevant DMETs in Vero E6 cells and postmortem lung tissues from COVID-19 patients. Also, we assessed the role of 2 inflammatory and 4 regulatory proteins in modulating the dysregulation of DMETs in human lung tissues. We showed for the first time that SARS-CoV-2 infection dysregulates CYP3A4 and UGT1A1 at the mRNA level, as well as P-gp and MRP1 at the protein level, in Vero E6 cells and postmortem human lung tissues, respectively. We observed that at the cellular level, DMETs could potentially be dysregulated by SARS-CoV-2-associated inflammatory response and lung injury. We uncovered the pulmonary cellular localization of CYP1A2, CYP2C8, CYP2C9, and CYP2D6, as well as ENT1 and ENT2 in human lung tissues, and observed that the presence of inflammatory cells is the major driving force for the discrepancy in the localization of DMETs between COVID-19 and control human lung tissues. Because alveolar epithelial cells and lymphocytes are both sites of SARS-CoV-2 infection and localization of DMETs, we recommend further investigation of the pulmonary pharmacokinetic profile of current COVID-19 drug dosing regimen to improve clinical outcomes.
ABSTRACT
The biological system of the oral cavity provides a number of protective mechanisms that fight pathogenic factors that arise due to a decrease in local immunity. This problem is found in patients after Covid-19. There is a violation of the blood supply to all organs and systems, including the mucous membrane of the oral cavity. As a result, patients have an increased risk of ulcers, plaques, fungal infections of the oral cavity, cracks, and spot hemorrhages. Due to a decrease in immune reactions in the oral cavity, the risk of caries in all groups of teeth increases, the permeability of enamel increases, and mineral substances exit from the hard tissues of the tooth.
ABSTRACT
Body fluids, cells, and tissues contain a wide variety of metabolites that consist of a mixture of various low-molecular-weight compounds, including amino acids, peptides, lipids, nucleic acids, and organic acids, which makes comprehensive analysis more difficult. Quantitative nuclear magnetic resonance (NMR) spectroscopy is a well-established analytical technique for analyzing the metabolic profiles of body fluids, cells, and tissues. It enables fast and comprehensive detection, characterization, a high level of experimental reproducibility, minimal sample preparation, and quantification of various endogenous metabolites. In recent times, NMR-based metabolomics has been appreciably utilized in diverse branches of medicine, including microbiology, toxicology, pathophysiology, pharmacology, nutritional intervention, and disease diagnosis/prognosis. In this review, the utility of NMR-based metabolomics in clinical studies is discussed. The significance of in vitro NMR-based metabolomics as an effective tool for detecting metabolites and their variations in different diseases are discussed, together with the possibility of identifying specific biomarkers that can contribute to early detection and diagnosis of disease.
ABSTRACT
Background: COVID-19 has spread rapidly around the world. It is necessary to study lung tissue of postmortem COVID19 patients to determine the molecular alteration particularly the role of IL-6 and IL-17 in causing fatality. Background: This study aims to determine the differences in the expressions of IL-6 and IL-17 in lung tissue of post-mortem COVID-19 patients compared to non-COVID-19 patients. This study also aimed to analyze the correlation between the expressions of IL-6 and IL-17 in lung tissue of post-mortem COVID-19 patients. Methods: This research is an observational analytic study with crosssectional approach. The samples were 15 paraffin blocks of post-mortem lung tissue biopsy of COVID-19 patients, and 15 paraffin blocks of inflammatory lung tissue biopsy or surgery of non-COVID-19 patients. IL-6 and IL-17 expressions were evaluated by immunohistochemical procedure. Result: There was a significant difference in the expression of IL-6 in the COVID-19 group and the non-COVID-19 group with a p-value = 0.001 (p < 0.05). There was a significant difference in the expression of IL-17 in the COVID-19 group and the non-COVID-19 group with p-value = 0.001 (p < 0.05). There was a significant correlation between the expressions of IL-6 and IL-17 in the COVID-19 group, with the Spearman coefficient value (rs) of 0.548 with p = 0.034 (p < 0.05). Conclusion: There are differences in the expression of IL-6 and IL-17 between COVID-19 and non-COVID-19 lung tissue. There is a significant correlation between the expressions of IL-6 and IL-17 in post-mortem lung tissue of COVID-19 patients.
ABSTRACT
Awareness of COVID-19 infection, as a public crisis, makes an emergency condition for survivors. Regarding the importance of early rehabilitation, we should pay particular attention to the potential risk of real-life toxicants in COVID-19 survivors. The adverse effects underlying COVID-19 infection lead to persistent sequelae in survivors. In addition, complete rehabilitation is challenging in seriously-ill patients due to cytokine storm severity, inflammation, oxidative stress, and cell death contributing to multi-organ damage. Different foods, environmental/occupational pollutants, and unhealthy lifestyles are real-life examples of toxicants that can pose redox imbalance and oxidative damage to the biological system. The key concept is that survived patients with persistent tissue damage, low-grade inflammation, oxidative stress, and fibrosis are susceptible to real-life toxic stressors, which have the potential for oxidative stress. Moreover, fibrosis are susceptible to toxic stressors, which can induce harmful effects by promoting oxidative stress and pro-inflammatory components. This paper attempted to elucidate a vital toxicological concept in which the existing sequelae of COVID-19 survivors increase the potential risk of real-life toxicants and to propose a practical strategic approach to reduce toxicant exposure.
ABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to diverse clinical manifestations and pathologies that involve multiple organs. Even though the disease severity is manifested mainly in the respiratory tract, which is the primary target of SARS-CoV-2 infection, acute kidney injury in the form of acute tubular necrosis has also been noted in some COVID-19 cases. It is not entirely clear whether renal cells can be infected by the virus that might be involved in acute kidney disorder. In a recent publication by Radovic and colleagues, that has been selected as the editor's choice paper published in the Journal of Medical Virology, the authors provided strong histopathological and immunofluorescence evidence of SARS-CoV-2 infection and tissue injury of renal parenchymal and tubular epithelial cells, which strongly suggest an active viral replication in the kidney of some severe and fatal COVID-19 cases, and to a lesser extent, a potential role for innate immune cells in viral infection and renal disease pathogenesis.
Subject(s)
Acute Kidney Injury , COVID-19 , Humans , COVID-19/pathology , SARS-CoV-2 , Kidney/pathology , Acute Kidney Injury/pathology , Epithelial CellsABSTRACT
BACKGROUND: Cross-border surrogacy and egg donor arrangements are an increasingly common means to family building. Establishing patterns of use has always been difficult in relation to Australian patients. Accurate data is stymied by lack of documentation of international third-party reproductive care available to Australian authorities. When international travel bans came into effect, it is hypothesised that those planning to use cross-border reproductive care had to rely significantly more on local in vitro fertilisation (IVF) clinics for services such as sperm freezing, embryo creation and gamete release procedures. AIM: To quantify and characterise the impact of the Covid-19-related travel ban on international and interstate gamete shipping by Australian IVF clinics. MATERIALS AND METHODS: Thirty-one Australian and New Zealand IVF clinics were invited to provide de-identified data on interstate and international gamete export applications from two 12 month time periods pre- and during Covid-19-related international travel lockdowns. Seven IVF organisations provided data on: patient age; type of gametes exported; destination country/state; and date gamete release approved. RESULTS: Most gametes (78%) were shipped to another Australian IVF clinic and 22% internationally. Patient-initiated shipping domestically and internationally both showed significant increases when comparing pre- and post-Covid datasets. Of the 21 destination countries reported for international shipments, the US was the commonest (39%), followed by Ukraine (21%) and Canada (9%). CONCLUSIONS: The inability of involuntarily infertile patients to travel internationally, rather than halt cross-border reproductive care, has led to a significant increase in the uptake of gamete shipping. The high proportion of internationally shipped gametes going to the US and Ukraine is likely a reflection of the availability of surrogates and donors and more amenable legal frameworks.
ABSTRACT
In December 2019, Coronavirus pandemic (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viruses, which affected the whole world, is emerged. The details on the epidemiology, infection source, transmission mode, and prognosis of SARS-CoV-2 gave in this review. Universal infection control standards such as hand hygiene, environmental cleanliness, use of personal protective equipment, and quarantine used to prevent the spread of COVID-19 without vaccine. However, many vaccine candidate studies carried out globally with using traditional and technological approaches. Innovations in technology allow the development of nanotechnological tools and the formation of systems that will inactivate SARS-CoV-2 in patients. It expected to include technologies that combine different disciplines, especially robotic applications, antimicrobial nanotechnology, and tissue engineering for the future treatment of COVID-19. This review-based work discusses the relationship of COVID-19 and nanotechnology based working principles. Copyright © 2023 Ayan, Aranci-Ciftci, Ciftci and Ustundag.
ABSTRACT
Background: The present study aims to evaluate how the measures to contain the SARS-CoV-2 spreading affected the surgical site infections (SSIs) rate in patients who underwent nondeferrable breast cancer surgery (BCS). Methods: This study is a retrospective analysis of prospectively collected data from a consecutive series of patients underwent nondeferrable BCS in a regional Italian Covid-free hub during two different period: March to April 2020 (pandemic cohort [PC]) and March till April 2019 (control cohort [CC]). SSIs were defined according to the criteria established by the Center for disease control and prevention (CDC) and additional treatment, serous discharge, erythema, purulent exudate, separation of deep tissues, isolation of bacteria, and stay (ASEPSIS) scoring systems. Results: One hundred ninety-nine patients were included in the present study: 100 and 99 patients who underwent nondeferrable BCS from March to April 2020 (PC) and from March to April 2019 (CC), respectively. The overall SSIs rate in this series was 9.1% according to CDC criteria and 6.5% according to ASEPSIS criteria. The SSIs incidence decreased during the pandemic period. Moreover, the SSIs rate according to ASEPSIS criteria was statistically lower in the PC than in the CC. We observed significant evidence of higher SSIs, both in terms of CDC and ASEPSIS score, in patients having undergone breast reconstruction compared with patients not undergoing immediate reconstruction. Conclusions: The restrictive measures issued during the lockdown period seemed to lower the SSIs rates in patients undergoing nondeferrable BCS.
ABSTRACT
Introduction: The SARS-CoV-2 pandemic has highlighted the need to understand the risk of infection that aerosolized particles pose to surgeons and clinical staff during otolaryngology procedures. The objective of our study is to determine whether hamster and human tissues generate similar amounts of aerosolized particles using common otolaryngology surgical techniques to establish the translational value of modeling aerosol generation in human tissue with animal models. Method(s): Drilling, electrocautery, and coblation were performed on human and hamster tissues. Particle size and concentration were measured during the surgical procedures using a scanning mobility particle sizer and an aerosol particle sizer (SMPS-APS) and GRIMM aerosol particle spectrometer. Result(s): SMPS-APS and GRIMM measurements detected at least 2-fold increases in aerosol concentrations compared with baseline during all procedures. Procedures performed on human and hamster tissues produced similar trends and order of magnitude of aerosol concentrations. Generally, hamster tissues produced higher aerosol concentrations compared with human tissues, and some of these differences were statistically significant. Mean particles sizes for all procedures were small (<200 nm), although statistically significant differences in particle size were identified between human and hamster tissues during coblation and drilling (P=.001 and P<.001, respectively). Conclusion(s): Aerosol-generating procedures performed on human and hamster tissue produce similar trends in aerosol particle concentrations and sizes, although we observed some differences between the two tissue types. Further studies should be performed to understand the clinical significance of these differences.
ABSTRACT
Background: Most neuropsychiatric disorders are moderately heritable but characterized by many genetic risk variants with weak effects. As such, it is difficult to point to direct causes or elucidate mechanisms of action. Despite the ease in gathering genetic data from humans, genetic data does not easily explain mechanistic effects. Gene expression on the other hand, which can more easily explain mechanistic effects, is harder to gather, especially in brain regions that are critical to the understanding of neuropsychiatric disease. To address this, we developed methods to impute genetically regulated gene expression (GReX) from genotypes and imputed GReX in over 440,000 European individuals in the Million Veteran Program (MVP) for a wide variety of tissues and cell types. Method(s): We use EpiXcan (based on PrediXcan) to develop machine learning models from training genotype, expression, and epigenetic data. We use custom scripts to impute individual GReX and perform a variety of downstream association analyses, including GReX Phenome Wide Association Studies (PheWAS) and Transcriptome Wide Association Studies (TWAS). Result(s): Results show an overlap in Schizophrenia genes identified by individual level TWAS and those identified by summary level TWAS informed by GWAS. TWASs for neuropsychiatric phenotypes identify genes established in the literature, but also novel targets. Inverse-variance meta-analyzed single gene imputation efforts across ancestries confirm clinical results obtained from COVID-19 positive individuals in both IL10RB and IFNAR2. GReX PheWAS for these particular genes using a novel negative binomial distribution for phecodes confirm COVID-19 related phenotypes. Finally, we describe various enriched pathways found in a COVID-19 TWAS, including immunological pathways. Discussion(s): GReX presents a unique solution to integrate effects across the genome and increase sample size in gene expression analyses. We are pursuing the creation of additional EpiXcan models, improved statistical methods for downstream association analyses, and replication efforts across biobanks. We plan to perform these analyses in all ancestries, available EpiXcan and PrediXcan models, and phenotypes. Disclosure: Nothing to disclose. Copyright © 2022
ABSTRACT
Introduction: The Portuguese government put into practice a vaccination plan soon after the approval of the first COVID-19 vaccine, prioritizing healthcare professionals (HCPs) and other population groups at risk. Objective: To characterize the case reports of adverse drug reactions (ADRs) associated with the administration of Comirnaty to HCPs in a Portuguese oncology hospital (IPO Coimbra). Methods: This study was a nine-month prospective, observational study following a cohort event monitoring approach focused on signalling ADRs associated with the administration of Comirnaty to HCP in IPO Coimbra. The case reports of ADRs were sent to the Pharmacovigilance Unit of Coimbra (UFC) between 14/01/2021 and 13/10/2021. The population of HCP was characterized according to gender and age distribution. The seriousness of ADRs was assessed for each individual case in accordance with WHO criteria [1]. ADRs were coded with MedDRA version 24.0 (System Organ Classification [SOC] and Preferred Term [PT]). ADRs were classified as expected or unexpected according to their description in the Summary of Product Characteristics (SmPC) of Comirnaty [2]. Results: A total of 816 HCPs were inoculated with at least one dose of Comirnaty. The case reports of ADRs concerned 469 (57.5%) HCPs: 386 (82.3%) females;642 (78.7%) aged 30-59 years old. Of the 469 case reports, 24 (5%) were assessed as serious, 44 (9.4%) as unexpected, and 11 (2.3%) as both serious and unexpected. The 469 case reports contained a total of 1,955 ADRs. "General disorders and administration site condition" (n = 1,075;54,9%), such as vaccination site pain, chills and vaccination site swelling;"Musculoskeletal and connective tissue disorders" (n = 373;19.1%), including myalgia and arthralgia;and "Nervous system disorders" (n = 250;12.8%), including headache, were the most frequently reported ADRs, which is in line with the SmPC of Comirnaty®. The 11 case reports classified as both serious and unexpected contained a total of 17 ADRs, including hyperhidrosis and paraesthesia. Conclusion: The results of this study bring value to the characterization of the safety profile of Comirnaty® since the use of a cohort of individuals allows to estimate frequencies of ADRs in the real-world. Further, serious, and unexpected ADRs were identified. Importantly, this type of safety data was further included in the SmPC of the vaccine. In conclusion, the results are in favour of the positive benefitrisk ratio of Comirnaty®, and reinforce the importance of post-marketing pharmacovigilance to increase knowledge on drug safety.
ABSTRACT
Introduction: European legislation on pharmacovigilance was amended with the adoption of EU Regulation 2010/1235 [1], which introduced significant changes in the active participation of patients and healthcare professionals to the Adverse Drug Reaction (ADR) reporting process. In recent years a new trend has established worldwide, allowing patients to directly report ADRs to national pharmacovigilance authorities [2]. A consumer, defined as a nonhealthcare professional, is now also considered as a source of information on the safety of a medicinal product [3]. Objective: To identify numerosity and level of the involvement of citizens in ADR reporting in Sardinia. Methods: We extracted data using Vigisegn platform from the Sardinian Region, from 2013 to 2021, for ADRs, stratified by year and qualification of the signaler. ADRs were also analyzed by severity, outcome, SOC (System Organ Classification) and ATC2 (Anatomical Therapeutic Chemical Classification System, level 2). Results: In Sardinia, from 2013 to 2021, 6.591 ADR reports were recorded, 1093 (17%) of which were by citizens. Among those reports, 75% were classified as "not serious" and 37% had resolved completely. From 2013 to 2021, citizen participation in ADR reporting changed significantly, from 1 to 26% (Table). In this period, most SOCs reported by citizens were "General pathologies and conditions related to site of administration" (596), "Pathologies of nervous system" (421), "Pathologies of musculoskeletal system and connective tissue" (328). As for SOC "Pathologies of reproductive system and breast", a significant increase in reporting was recorded: from 0% in 2013 to 73% in 2021. In this period, citizen reporting of pathologies of reproductive system and breast constituted 49% of the total reports. In absolute terms, the ATC J07 Vaccine was the most reported by citizens with 799 reports (2737 in 2021). Reports by citizens for homeostatic calcium drugs (H05) account for 81% (48 ADRs) of the total reports for this ATC. Conclusion: Increase in citizen reporting in 2017 and 2021 can be traced back to the information activities of the Regional Center following the introduction of mandatory vaccination and the awareness campaign for Covid-19 vaccines. Such increase reflects the growing importance of pharmacovigilance among citizens, meaning that an increasing number of citizens have now acquired the necessary tools to ADR reporting, thus becoming a significant source of information on the safety of drugs and vaccines.
ABSTRACT
Introduction: Dermatomyositis is an idiopathic autoimmune connective tissue disease. It is typically characterized by proximal muscle weakness and skin rashes. Dermatomyositis is associated with a higher risk of malignancy compared to the general population (1). One case in literature has reported a dermatomysitis post COVID-19 vaccination (2). Objective: Case report. Methods: We report a case of dermatomyositis following Covid-19 immunization, notified to the National Centre of Pharmacovigilance of Tunis in May 2021. Results: A 33 year old woman, with no significant past medical history. She developed in March 2021, two days after 1st dose Pfizer BioNTeh Covid-19 vaccination, a mild facial erythema and ipsilateral auxiliary adenopathy. The evolution was marked by a persistence of the erythema and a regression of the adenopathy In April 2021, 2 days following the 2nd dose, she presented an accentuation of the symptomatology: skin erythema and edema in the photo-exposed areas: face, neck and upper limbs. As well as a diffuse myalgia in upper and lower limbs. She was afebrile and didn't present itchiness. The patient received intravenous methylprednisolone 1 injection per day for 5 days, followed by 1 mg/kg prednisolone and anti histaminic drugs without amelioration. The diagnosis of dermatomyositis was suspected in view of the persistence of the symptoms 1 month after vaccination and the installation of a proximal muscular deficit. Laboratory studies revealed a high level of creatine phosphokinase (CPK) at 3800 UI/l (< 140) and Lactate dehydrogenase (LDH) at 628 UI/l (< 248). The skin biopsy showed an aspect consistent with a moderate inflammatory myopathy. Autoimmune serology revealed the presence of anti-nuclear antibodies (ANA) (1/100) and a positive anti-Mi-2 antibodies. The patient underwent thorough malignancy screening. Findings of cervico-thoraco-abdomen pelvic scan didn't reveal any evidence for solid organ malignancies or interstitial lung disease. However, the mammogram and ultrasound-guided biopsy has identified an invasive carcinoma. Conclusion: This case showed a dermatomyositis case suspected initially to be associated to mRNA COVID vaccination which was finally related to a breast cancer.
ABSTRACT
Introduction: Gastrointestinal stromal tumors (GISTs), soft tissue sarcomas of the digestive tract, are associated with oncogenic mutations that led to the approval of tyrosine kinase inhibitors (TKIs) [1-2]. Considering the increased use of TKIs in clinical practice, it may be useful to identify unexpected adverse drug reactions (ADRs). Objective: The aim of this study was to describe better ADRs and to identify unexpected potential safety signals through the analysis of individual case safety reports (ICSRs) among TKIs approved for GIST collected into the European Spontaneous Reporting System (SRS) database. Methods: All ICSRs recorded starting from the drug approval up to 31 December 2021 with one of the following TKIs reported as suspected drug were included: imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP). A descriptive analysis was conducted to assess all demographic characteristics. Moreover, a disproportionality analysis was performed using the Reporting Odds Ratio (ROR) with the corresponding 95% Confidence Interval (CI) to evaluate the frequency of ADRs for each TKI compared to all other TKIs. Results The number of analyzed ICSRs was 8,512 (Figure 1 Flowchart of ICSRs selection process): the 57.9% were related to IM, followed by SU (24.2%), AVA (13.1%), REG (2.7%), and RIP (2.1%). ICSRs were mainly serious (87.5%), related to males (51.7%), and to adults (44.7%);moreover, the 25.5% were fatal. The disproportionality analysis showed a higher reporting frequency of some unexpected ADRs for each TKI: gait disturbance (ROR 2.86;95% CI 1.90-4.29), hyperhidrosis (2.57;1.06-6.20), and hyperammonemia (3.92;1.05-14.60) for SU;cerebrovascular accident (6.23;2.18-17.84), hemoglobin decreased (2.23;1.08-4.61), and internal haemorrhage (14.44;3.94-52.92) for RIP;gastrointestinal ulcer (10.88;2.98-39.81) for REG;hepatic and lung cancer for IM (12.79;8.04-20.37 and 7.71;3.33-17.84, respectively);hallucination (24.33;9.02-65.68), mood swings (8.02;2.44-26.33), and stress (6.68;1.93-23.11), nephrolithiasis (6.69;2.15-20.77), pollakiuria (3.08;1.17-8.13), and dialysis (6.68;1.67-26.73), sinusitis (3.34;1.14-9.78), cellulitis (4.17;1.36-12.78), and COVID-19 (7.25;3.40-15.45), chills (2.36;1.22-4.58), limb fracture (3.53;1.63-7.60), hernia (9.23;3.71-23.00), diabetes mellitus (5.02;2.11-11.95), hyposideraemia (5.02;2.11-11.95), tinnitus (3.64;1.34-9.87), parosmia (5.00;1.12-22.38), Raynaud's phenomenon (5.00;1.12-22.38), and thyroid function test abnormal (8.90;1.99-39.83) for AVA. Conclusion: This study is largely consistent with results from literature but some unexpected ADRs were shown. Further studies are necessary to increase the awareness about the safety profiles of new TKIs approved for GISTs.
ABSTRACT
Introduction: The European Medicines Agency, following positive evaluation regarding the safety, quality, and efficacy of anti-COVID19 vaccines, granted conditional marketing authorization (CMA) for these drugs on the condition that the developers would continuously provide additional data on their safety and efficacy even after marketing authorization in order to confirm the risk-benefit ratio. Following the start of the vaccination campaign in December 2020, special attention was paid to the occurrence of possible adverse reactions (ADRs). The pharmacist staff of Pugliese-Ciaccio Hospital, in order to monitor the safety of the new vaccine and to promptly report suspected vaccine ADRs, prepared a short questionnaire to be administered to the employees of the hospital at the time of administration of the second dose of vaccine. Objective: Monitoring vaccine safety & promptly reporting side effects. Methods: The survey was conducted between January and April 2021. All employees were administered mRNA vaccine and, at the time of the administration of the second dose, were asked to answer the above questionnaire specifying the following information: biographical data, gender, date of administration of the two doses of vaccine, occurrence of any ADRs resulting from the first dose of vaccine, type of resolution, presence of concomitant diseases and related medication intake in the days before/following the vaccination. Results: The questionnaire was administered to 1,656 health care workers and all of them answered the questions comprehensively. Among them, 51.6 percent experienced adverse reactions after administration of the first dose of vaccine, and the predominantly noted symptoms included systemic diseases and conditions related to the site of administration, musculoskeletal and connective tissue disorders, nervous system disorders and gastrointestinal disorders. The frequency of reporting was higher among the young than the elderly population (58% vs. 38.67%). ADRs occurred approximately 1,7 times more frequently among women than men. Conclusion: The intense pharmacovigilance activity carried out by the Hospital Pharmacist was a pivotal moment during the pandemic emergency, as it allowed the safety profile of anti-COVID-19 vaccines to be readily confirmed with real-life data. Infact, it was found that the main symptoms detected were in line with what was reported in the safety data from the pre-registration studies [1], from which it was also found that the frequency of ADRs was higher among the young than the elderly, a finding that was also confirmed by our study. So, the questionnaire survey was able to substantiate the safety of vaccines, confirming that the benefits of vaccination outweigh the risks.
ABSTRACT
Introduction: As part of vaccines surveillance, a reinforced surveillance strategy for Covid-19 vaccines adverse events following immunization (AEFI) was set up in Tunisia. This strategy was conducted since the Covid-19 vaccination campaign has been started in March 2021. The safety profile of available vaccines was monitored in real time to ensure security of the population and to be able to anticipate coincidental events that might be attributed to the vaccine. Objective: to analyze the reported AEFI associated with different types of COVID-19 vaccines. Methods: A descriptive study on AEFI from Covid-19 vaccines collected at the National Chalbi Belkahia Center for Pharmacovigilance (CNPV) from March 13th 2021 to May 22, 2022. During this period, vaccines used were Pfizer BioNTech®, Vaxzevria®, Spikevax®, Janssen®, Sputnik V®, Coronavac®, and Sinopharm®. Results: We collected 3116 AEFI on 13 173 137 COVID-19 vaccines administered doses (0.02%). The mean age was 48.8 years [13-98]. The sex ratio M/F was 0.59. The vaccines mainly used were the Pfizer BioNTech® vaccine in 51.6%, Vaxzevria® in 16.1%, Spikevax® in 10.9% and Janssen® in 7.6% of cases. AEFI SOCs were general manifestations and injection site reactions (44%), nervous system disorders (27.4%), musculoskeletal and connective tissue disorders (16.4%), Skin and subcutaneous tissue disorders (16.2%), gastrointestinal disorders (12.1%), respiratory, thoracic and mediastinal disorders (6.7%), immune system disorders (5.9%), vascular disorders (5.8%), infections and infestations (5.7%), Injury, poisoning and procedural complications (5.5%), Ear and labyrinth disorders (4.9%), cardiac disorders (4.6%), and others (9.2%). The most reported MedDRA terms were fever (20.2%), asthenia (16.9%), headache (13.8%), injection site pain (9.4%), and muscle pain (8.9%). Serious AEFI were noted in 7% of AEFI. SOCs were Nervous system disorders (38.7%), Cardiac disorders (17.5%), General disorders and administration site conditions (15.2%), vascular disorders (12.9%), Infections and infestations (12.4%), Respiratory, thoracic and mediastinal disorders (7.8%), Skin and subcutaneous tissue disorders (6.5%), and others (21.2%). The most used vaccines in serious AEFI Pfizer BioNTech® in 47%, Vaxzevria® in 21.2% and Coronavac® in 11.1%. Conclusion: This study confirms clinical trials data in which the most frequent AEFIs were general and injection site disorders. Serious adverse event were rare. These results show that the benefit of vaccination outweighs the risk and encourage vaccination