The interplay between viral molecular mimicry and host chromatin dynamics.

Molecular mimicry is a commonly used mechanism by viruses to manipulate host cellular machinery and coordinate their life cycles. While histone mimicry is well studied, viruses also employ other mimicry strategies to affect chromatin dynamics. However, the relationship between viral molecular mimicry and host chromatin regulation is not well understood. This review summarizes recent advances in histone mimicry and explores how viral molecular mimicry influences chromatin dynamics. We also discuss how viral proteins interact with both intact and partially unfolded nucleosomes and compare the distinct mechanisms governing chromatin tethering. Finally, we address the role of viral molecular mimicry in regulating chromatin dynamics. This review provides new insights into viral molecular mimicry and its impact on host chromatin dynamics, paving the way for the development of novel antiviral strategies.

Molecular mimicry and autoimmunity in the time of COVID-19.

Infectious diseases are commonly implicated as potential initiators of autoimmune diseases (ADs) and represent the most commonly known factor in the development of autoimmunity in susceptible individuals. Epidemiological data and animal studies on multiple ADs suggest that molecular mimicry is one of the likely mechanisms for the loss of peripheral tolerance and the development of clinical disease. Besides molecular mimicry, other mechanisms such as defects in central tolerance, nonspecific bystander activation, epitope-determinant spreading, and/or constant antigenic stimuli, may also contribute for breach of tolerance and to the development of ADs. Linear peptide homology is not the only mechanism by which molecular mimicry is established. Peptide modeling (i.e., 3D structure), molecular docking analyses, and affinity estimation for HLAs are emerging as critical strategies when studying the links of molecular mimicry in the development of autoimmunity. In the current pandemic, several reports have confirmed an influence of SARS-CoV-2 on subsequent autoimmunity. Bioinformatic and experimental evidence support the potential role of molecular mimicry. Peptide dimensional analysis requires more research and will be increasingly important for designing and distributing vaccines and better understanding the role of environmental factors related to autoimmunity.

Idiotope-Driven T-Cell/B-Cell Collaboration-Based T-Cell Epitope Prediction Using B-Cell Receptor Repertoire Sequences in Infectious Diseases.

T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore, important for understanding diverse immune responses and controlling T-cell immunity. A number of bioinformatic tools exist that predict T-cell epitopes; however, many of these methods highly rely on evaluating conventional peptide presentation by major histocompatibility complex (MHC) molecules, but they ignore epitope sequences recognized by T-cell receptor (TCR). Immunogenic determinant idiotopes are present on the variable regions of immunoglobulin molecules expressed on and secreted by B-cells. In idiotope-driven T-cell/B-cell collaboration, B-cells present the idiotopes on MHC molecules for recognition by idiotope-specific T-cells. According to the idiotype network theory formulated by Niels Jerne, such idiotopes found on anti-idiotypic antibodies exhibit molecular mimicry of antigens. Here, by combining these concepts and defining the patterns of TCR-recognized epitope motifs (TREMs), we developed a T-cell epitope prediction method that identifies T-cell epitopes derived from antigen proteins by analyzing B-cell receptor (BCR) sequences. This method allowed us to identify T-cell epitopes that contain the same TREM patterns between BCR and viral antigen sequences in two different infectious diseases caused by dengue virus and SARS-CoV-2 infection. The identified epitopes were among the T-cell epitopes detected in previous studies, and T-cell stimulatory immunogenicity was confirmed. Thus, our data support this method as a powerful tool for the discovery of T-cell epitopes from BCR sequences.

Autoimmune Peripheral Neuropathies

Autoimmune peripheral neuropathies (APNs) occur when immunological tolerance to peripheral nerve components (myelin, axon, or ganglionic neurons) is lost. The most common APNs are acute inflammatory polyneuropathies, such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), immunoglobulin M (IgM)–anti–myelin-associated glycoprotein (MAG) antibody–mediated paraproteinemic neuropathy, and those caused by vasculitis or viral infections. Both cellular and humoral factors, either independently or in concert with each other, appear to play a role, but the specific immune mechanisms have not been fully elucidated. Infectious agents, such as Campylobacter jejuni and Zika virus via molecular mimicry, and now COVID-19, are implicated in some GBS subtypes, but the factors that break tolerance in the other APNs remain unknown. In some acute or chronic APN, antibodies against peripheral nerve glycolipids or glycoproteins are pathogenic and well characterized. Pathogenic IgG4 antibodies against antigens at the nodes of Ranvier that cause disadhesion of nodal and paranodal proteins and conduction block define distinct CIDP subtypes, which respond only to rituximab. Some newly emerging, not pathogenic, autoantibodies more commonly seen in small fiber sensory neuropathies and neuropathic pains are briefly discussed. The current immunotherapies in all APNs are described based on controlled trials or clinical experience. © 2023 Elsevier Ltd. All rights reserved.

A Case of Ocular Myasthenia Gravis Seen by Rheumatology as Suspected Mononeuritis Multiplex in an Adult Male Shortly after Pfizerbiontech Sars-Cov-2 Vaccination

Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.

Structural similarity between thyroid peroxidase [Homo sapiens] and SARS-CoV-2 spike glycoprotein ­ An autoimmune thyroiditis triggering mechanism in COVID-19 carriers? / Similaridade estrutural entre a tireoperoxidase humana [Homo sapiens] e a glicoproteína de superfície do SARS-CoV-2 ­ Um mecanismo de desencadeamento da tiroidite autoimune nos portadores da COVID-19?

Introduction: there are reports of autoimmune disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such neurological syndromes and hematological syndromes, and more recently autoimmune thyroid dysfunctions have been described. These reports suggest that SARS-CoV-2 acts as a probable trigger for triggering the autoimmunity process. Aim: to evaluate structural similarity between thyroid peroxidase [Homo sapiens] (TPO) and SARS-CoV-2 spike glycoprotein (COVID-19), and to propose this similarity as a likely trigger for autoimmune thyroiditis. Methodology: using bioinformatics tools, we compare the amino acids (AA) sequences between protein structure of TPO and chain A COVID-19, chain B COVID-19, and chain C COVID-19, accessible in the National Center for Biotechnology Information database, by Basic Local Alignment Search Tool in order to locate the homologous regions between the sequences of AA. Results: the homology sequence between the TPO and COVID-19 ranged from 27.0 % (10 identical residues out of 37 AA in the sequence) to 56.0% (5 identical residues out of 9 AA in the sequence). The similar alignments demonstrated relatively high E values in function of short alignment. Conclusion: data suggest a possible pathological link between TPO and COVID-19. The structural similarity of AA sequences between TPO and COVID-19 may present a molecular mimicry suggesting the possibility of antigen crossover between TPO and COVID-19 that might represent an immunological basis for autoimmune thyroiditis associated with COVID-19.

Introdução: há relatos de doenças autoimunes relacionadas à síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2), tais como síndromes neurológicas e hematológicas, e mais recentemente disfunções autoimunes da tireoide foram descritas. Esses relatos sugerem que o SARS-CoV-2 atue como um provável gatilho para desencadear o processo de autoimunidade. Objetivo: avaliar a similaridade estrutural entre a peroxidase tireoidiana [Homo sapiens] (TPO) e a glicoproteína de superfície SARS-CoV-2 (COVID-19) e propor essa similaridade como provável gatilho para o desencadeamento da tireoidite autoimune. Metodologia: utilizando ferramentas de bioinformática, comparamos as sequências de aminoácidos (AA) entre a estrutura da TPO e a estrutura da cadeia A do COVID-19, a cadeia B do COVID-19 e a cadeia C do COVID-19, acessível no banco de dados do National Center for Biotechnology Information, através da Ferramenta Básica de Pesquisa de Alinhamento Local para localizar as regiões homólogas entre as sequências de AA. Resultados: a sequência de homologia entre o TPO e COVID-19 variou de 27,0% (10 resíduos idênticos em 37 AA nas sequências) a 56,0% (5 resíduos idênticos em 9 AA nas sequências). Os alinhamentos semelhantes demonstraram valores E relativamente altos em função do alinhamento curto. Conclusão: os dados sugerem uma possível ligação patológica entre TPO e COVID-19. A similaridade estrutural das sequências de AA entre TPO e COVID-19 pode apresentar um mimetismo molecular sugerindo a possibilidade de cruzamento de antígeno entre TPO e COVID-19 que podem representar uma base imunológica para tireoidite autoimune associada a COVID-19.

Thyroid Eye Disease Following COVID-19 Infection in a Patient with a History of Graves' Disease

Introduction: Autoimmune and inflammatory thyroid diseases have been reported following SARS-CoV-2 infection or vaccination, but thyroid eye disease (TED) post-COVID-19 infection is less common. We describe a case of TED following SAR-CoV-2 infection in a patient with a history of Graves' disease. Case Description: A 59-year-old female with history of Graves' disease status post radioiodine ablation therapy in 2002. She developed post-ablative hypothyroidism which has been stable on levothyroxine 88 mcg daily. In January 2021, the patient's husband and daughter were diagnosed with COVID-19 infection. A few days later, the patient developed an upper respiratory tract infection associated with loss of sense of smell and taste consistent with COVID-19 infection. Three days later, she developed bilateral watery eyes which progressed to eye redness, eyelid fullness, retraction, and pain with eye movement over 1-month duration. Her eye examination was significant for severe periocular soft tissue swelling, lagophthalmos and bilateral exophthalmos. The laboratory workup was consistent with normal TSH 0.388 mIU/L (0.358-3.740 mIU/L) and positive TSI 1.01 (0.0-0.55). The patient was referred to an Ophthalmologist for evaluation of TED. He noted bilateral exophthalmos, no restrictive ocular dysmotility or compressive optic neuropathy (clinical activity score 4/7 points). CT scan of orbit showed findings compatible with thyroid orbitopathy. Based on clinical activity score of 4, treatment with Teprotumumab was recommended pending insurance approval. Discussion(s): Many cases of new-onset Graves' hyperthyroidism have been reported after COVID-19, with only a few associated with TED. Our patient has been in remission for 20 years before she developed COVID-19 infection with occurence of TED.This suggests that COVID-19 infection may have played a role. SARS-CoV-2 may act through several mechanisms, including breakdown of central and peripheral tolerance, molecular mimicry between viral and self-antigens, stimulation of inflammasome with release of type I interferon. In our patient, treatment with Teprotumumab was indicated due to Graves' orbitopathy clinical activity score greater than or equal to 3. In conclusion, it is very uncommon for TED to present after COVID-19 infection. Our case reinforces the speculative hypothesis that SARS-CoV-2 virus could have triggered an autoimmune response against eye antigens. There is a need for increased awareness about the link between COVID-19 and autoimmunity to help better define the management of patients.Copyright © 2023

Silent Thyroiditis as a Complication of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine

Introduction: Silent autoimmune thyroiditis, a type of chronic autoimmune thyroiditis, as an adverse effect of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is infrequently reported in the literature. We hereby describe a case of silent thyroiditis followed by Grave's orbitopathy after vaccination against SARS-CoV2. Case Description: An 84-year-old male presented to clinic with a 10-pound weight loss with no other symptoms of hyperthyroidism, no personal history of thyroid illnesses, or recent viral infections. He had normal thyroid function 3 months prior to presentation. He had received 3 doses of SARS-CoV2 Pfizer-BioNTech vaccine with the last dose 5 months prior to presentation. Thyroid exam was normal. Laboratory testing revealed thyroid stimulating hormone (TSH) level of 0.005 IU/ml (0.45-4.5 IU/ml), total T4 14.4 g/dl (4.5-12.1 g/dl), and total T3 1.22 nmol/l (0.6-1.81 nmol/l). Thyroid Ultrasound revealed a heterogeneous atrophic thyroid gland with no nodules or hypervascularity. He was started on Methimazole by primary care provider. Four months later, he was seen in the Endocrinology clinic and reported no hyperthyroidism symptoms. His TSH level at that time was 65.9 IU/ml, free T4 0.47 ng/dl (normal: 0.82-1.77 ng/dl), total T3 level 75 ng/dl (normal: 71-180 ng/dl), thyroid stimulating immunoglobulin 2.05 IU/l (0-0.55 IU/L), thyrotropin receptor antibody level 2.8 (0-1.75). Methimazole was discontinued. At 6 months after initial presentation laboratory testing showed TSH 5.010 IU/ml, free T4 1.2 ng/dl, thyroid peroxidase antibody of 148 IU/ml (normal 0-34 IU/ml), thyroglobulin antibody 131.6 IU/ml (normal 0.0-0.9 IU/ml). He was diagnosed with silent autoimmune thyroiditis. A few weeks later, the patient presented to an ophthalmologist with bilateral eye bulging and impaired vision. He was diagnosed with acute Graves' orbitopathy and started on pulse-dose of intravenous Methylprednisolone 250 mg twice daily and urgently referred to a tertiary ophthalmology center for teprotumumab infusion. His thyroid function tests were normal at that time on no thyroid medications. Discussion(s): The underlying mechanisms of thyroid impairment following SARS-CoV2 vaccination are not completely understood. There is a role of molecular mimicry between SARS-CoV2 antigens and thyroid antigens that may help to hasten the emergence of autoimmunity in vulnerable individuals. Our patient developed multiple thyroid-related antibodies following vaccination. Silent painless thyroiditis is a self-limiting condition, characterized by temporary thyrotoxicosis, followed by a brief period of hypothyroidism and then a complete return to normal thyroid function. A radioactive iodine uptake scan can help differentiate between the different causes of thyrotoxicosis in the acute thyrotoxic phase. Development of severe Graves orbitopathy following silent autoimmune thyroiditis after SARS COV2 vaccination has not been previously reported.Copyright © 2023

New Onset of Type 1 Diabetes After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination

Introduction: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses the greatest threat of our times. SARS-CoV-2 vaccines are one of the most effective strategies against this infection. Diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, and new-onset diabetes as adverse effects of SARS-CoV-2 vaccination have been infrequently described in the literature. We hereby report a rare case of new-onset type 1 diabetes after SARS-CoV-2 vaccination. Case Description: An 18-year-old male presented to the outpatient office for evaluation of breast pain. On routine laboratory tests, he was noted to have fasting blood glucose of 200 mg/dL. On further questioning, he reported some polyuria, nocturia, and a 10-pound weight loss over the preceding month. He received the initial dose of Pfizer-BioNTech SARS-CoV-2 vaccine in May 2022 and the second dose in June 2022, approximately one month before the onset of symptoms. He denied any earlier viral infections and had no personal or family history of autoimmune conditions. On evaluation, his body mass index was 20 kg/m2, but otherwise, he had a normal physical exam, including a breast exam. Over the next few days, his blood glucose progressively increased to over 300 mg/dl. HbA1c was noted to be elevated at 8.6%, glutamic acid decarboxylase-65 (GAD-65) antibodies were remarkably high >250 IU/ml (normal 5 IU/ml), C-peptide was 1.51 ng/ml (normal 0.80 - 3.85 ng/ml), blood glucose 156 mg/dl, islet-cell antibody titer was 320 (< 1.25 JDF units) and insulin autoantibodies were negative. He was diagnosed with autoimmune Type 1 diabetes and a basal-bolus insulin regimen was initiated to improve glycemic control. On a one-month follow-up, his insulin requirements remained low but persistent and his glycemic control was acceptable. Discussion(s): Various viruses are known to play a fundamental role in the onset of type 1 diabetes via a variety of effects on pancreatic beta-cells because of either the direct lytic effects of viral replication or the inflammatory response to the virus, which is mediated by autoreactive T cells. The limited release of islet cell antigens induces molecular mimicry and paves the way for long-term autoimmunity and the development of type 1 diabetes mellitus. Our patient did not report any viral illnesses before the onset of his symptoms. He also did not have a family or personal history of autoimmune diseases. His onset of diabetic symptoms coincided temporally with receiving the SARS-CoV-2 vaccine. The detection of a considerable titer of GAD-65 antibodies proved autoimmunity. Clinicians must stay vigilant about this potential side effect of SARS-CoV2 vaccine so that a timely diagnosis can be made.Copyright © 2023

New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves' Disease Post-Radioactive Iodine Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves' Disease (GD) even after treatment with radioactive iodine (RAI). Case Description: In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. Discussion(s): GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.Copyright © 2023

Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis.

Molecular mimicry between foreign and self-antigens has been implicated as a cause of autoimmune hepatitis in experimental models and cross-reacting antibodies in patients. This review describes the experimental and clinical evidence for molecular mimicry as a cause of autoimmune hepatitis, indicates the limitations and uncertainties of this premise, and encourages investigations that assess diverse environmental antigens as sources of disease-relevant molecular mimics. Pertinent articles were identified in PubMed using multiple search phrases. Several pathogens have linear or conformational epitopes that mimic the self-antigens of autoimmune hepatitis. The occurrence of an acute immune-mediated hepatitis after vaccination for severe acute respiratory syndrome (SARS)-associated coronavirus 2 (SARS-CoV-2) has suggested that vaccine-induced peptides may mimic disease-relevant tissue antigens. The intestinal microbiome is an under-evaluated source of gut-derived antigens that could also engage in molecular mimicry. Chaperone molecules may enhance the pathogenicity of molecular mimics, and they warrant investigation. Molecular mimics of immune dominant epitopes within cytochrome P450 IID6, the autoantigen most closely associated with autoimmune hepatitis, should be sought in diverse environmental antigens and assessed for pathogenicity. Avoidance strategies, dietary adjustments, vaccine improvement, and targeted manipulation of the intestinal microbiota may emerge as therapeutic possibilities. In conclusion, molecular mimicry may be a missing causality of autoimmune hepatitis. Molecular mimics of key immune dominant epitopes of disease-specific antigens must be sought in diverse environmental antigens. The ubiquity of molecular mimicry compels rigorous assessments of peptide mimics for immunogenicity and pathogenicity in experimental models. Molecular mimicry may complement epigenetic modifications as causative mechanisms of autoimmune hepatitis.

Exposure to SARS-CoV-2 and Infantile Diseases.

Background and Aim Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can-via molecular mimicry and the consequent cross-reactivity-also hit human proteins involved in infantile diseases. Methods Human proteins that-if altered-associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena. Results Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible. Conclusion Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela.

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin.

The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by KD to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1-4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed.

Risk of autoimmune diseases in patients with COVID-19 a retrospective cohort study

Background There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.Methods This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.Findings Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjogren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behcet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24).Interpretation COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.Funding Kaohsiung Veterans General Hospital (KSVGH111-113).

New-onset Thyroid Eye Disease after COVID-19 Vaccination in a Radioactive Iodine-Treated Graves' Disease Patient: A Case Report and Literature Review.

Autoimmunity associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been well-described as the mechanism of development of thyroid dysfunction following Coronavirus Disease 19 (COVID-19) infection and SARS-CoV-2 vaccination. However, the occurrence of thyroid eye disease (TED) after SARS-CoV-2 vaccination is scarcely described. The postulated mechanisms include immune reactivation, molecular mimicry and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). We report a case of new-onset TED after receiving the SARS-CoV-2 vaccine.

Postvaccination immune-mediated hepatitis: what do we really know?

Tweetable abstract The percentage of patients with immune-mediated vaccine-associated hepatitis is minimal compared with the number of patients vaccinated worldwide.

Symptomatic Myocarditis After Pfizer Covid-19 Vaccination

Widely considered safe, effective, and essential for pathogenic immunity, vaccines have proven to be one of the most important discoveries to date in medicine. Adverse reactions to vaccines are typically trivial but there have been extremely rare reports of vaccine induced myocarditis, particularly with the Tdap vaccine. This is thought to be due to a hypersensitivity reaction. In efforts to combat the SARS-CoV-2, prompt response from Pfizer-BioNTech and Moderna lead to vaccine development with a novel method, synthesized from modified messenger RNA. Despite minimal side effects on initial trials, reports of vaccine induced myocarditis have resulted. A majority of these cases occurred following subsequent doses for those previously inoculated. A descriptive study published in JAMA in January 2022 reviewed the Vaccine Adverse Event Reporting System (VAERS) in collaboration with the CDC described only 1626 cases of myocarditis, of which the majority occurred within days of the second dose. This review was limited by reviewing a passive reporting syndrome with variable quality data and without follow up data post diagnosis of myocarditis. Here we present a case of myocarditis occurring less than 24 hours after the second dose of Pfizer-BioNTech vaccine with 3 month follow up. A 23 year old man received his second dose of the COVID-19 vaccine in the morning. Within a few hours he experienced chest pain, chills, weakness, and fatigue. These dissipated by 7pm. He is a member of the National Guard and during drills the next day experienced stabbing substernal chest pain for which he sought evaluation. The pain radiated into his left jaw, worse with deep inspiration and worse in the left lateral decubitus position. He is a 1 PPD smoker with no personal or family history or cardiac disease. A friction rub was heard on physical exam. His troponin I peaked at 2.6ng/mL. His EKG showed normal sinus rhythm, a TTE showed a normal EF with no pericardial effusion. He was given aspirin 81 mg and started on a heparin drip for possible NSTEMI. The next day his pain decreased and a cardiac MRI demonstrated no inflammation. His serum coxsackie and parvovirus titers were negative. He was instructed to continue the aspirin, limit exercise for 8 weeks, and stop smoking. Upon follow up 3 months later the patient denied any recurrent chest pain and was advised to continue the aspirin. But the original bout of myocarditis limited his participation in the National Guard. Our case illustrates that exposure to an immunological trigger, the COVID-19 vaccine, leading to myocarditis was extremely short compared to typical cases of viral induced or vaccine hypersensitivity reaction. A proposed mechanism is molecular mimicry between the spike protein and myocardial contraction proteins. It also demonstrates that the vaccine can cause morbidity in patients, especially younger males. It also exemplifies that this may be a short lived phenomenon, long term follow up is still needed. With the rate of vaccination increasing, there needs to be a low threshold to consider myocarditis in young adults who have new chest pain after receiving an mRNA based vaccine.Copyright © 2022

[Importance of autoimmunity induced by SARS-CoV-2 and development of post-vaccination autoimmune diseases]. / Importancia de la autoinmunidad inducida por SARS-CoV-2 y desarrollo de enfermedades autoinmunes post-vacunación.

SARS-CoV-2, a virus belonging to the large family of coronavirus, aroused great interest following the outbreak of this new strain reported in 2019, in Wuhan China. Its clinical spectrum is highly variable, ranging from a self-limited disease to an acute respiratory distress syndrome with systemic clinical manifestations (COVID-19), in which the immune system plays a key role in the pathophysiology of this disease and in its severity; several studies show the prevalence of some autoimmune markers suggesting that they may lead to autoimmune states. The most important strategy worldwide to protect the population was the development of vaccines to induce immunity to severe COVID-19; however, vaccines have also been shown to have the ability to produce autoimmune states in a small percentage of the world's population; nevertheless, the best strategy remains vaccination. The aim of this review is to show the current overview of the mechanisms of SARS-CoV-2-induced autoimmunity and post-vaccination for a better understanding and identification of these in the population. Publications from 2019 to 2022 were reviewed in PubMed as the primary search source.

El SARS-CoV-2, un virus perteneciente a la gran familia de los coronavirus despertó gran interés después del brote de la nueva cepa reportada en 2019, en Wuhan, China. Las manifestaciones clínicas son variables: desde enfermedad con curación espontánea hasta síndrome de dificultad respiratoria aguda, con alteraciones clínicas sistémicas (COVID-19), donde el sistema inmunitario tiene participación importante en la fi-siopatología de la enfermedad y su gravedad. Diversos estudios demuestran la prevalencia de algunos marcadores autoinmunes, lo que sugiere que pueden conducir a estados de autoinmunidad. La estrategia más importante a nivel mundial para proteger a la población fue el desarrollo de vacunas para inducir inmunidad frente al COVID-19 grave; sin embargo, se ha demostrado que tienen la capacidad de producir estados autoinmunitarios en un pequeño porcentaje de la población; no obstante, siguen siendo la mejor estrategia de tratamiento. El objetivo de esta revisión es mostrar el panorama actual de los mecanismos de autoinmunidad inducidos por SARS-CoV-2 y la post-vacunación, para una mejor comprensión e identificación en la población. Se revisaron las publicaciones de 2019 a 2022 en PubMed como fuente principal de búsqueda.

A Case of COVID-19-Induced Immune Thrombocytopenia (ITP) in an Adult Female: An Under-Recognized Emerging Phenomenon.

Coronavirus disease 2019 (COVID-19) follows a mild course in majority of cases, but some patients may develop non-pulmonary yet life-threatening complications. A Pandora's box had been opened when multisystem hyper-inflammatory syndromes and autoimmune diseases that had been described previously in children and young adults, that are associated with COVID-19, have now emerged in adults. They need to be recognized as important sequelae of severe COVID-19 disease. Immune thrombocytopenia (ITP) or thrombocytopenic purpura is an autoantibody and T-cell-mediated autoimmune disorder characterized by isolated thrombocytopenia, which can be triggered by different infections. First-line treatment of severe ITP includes platelet transfusions in life-threatening cases, followed by corticosteroids and intravenous immunoglobulins (IVIG). Since the beginning of the pandemic, more and more cases of COVID-19-associated ITP have been reported. We report a case of acquired ITP in a young woman that could only be attributed to her COVID-19 infection and was refractory to platelet transfusion, requiring further treatments. The aim of this report is to review some of the etiologies and purposed molecular mechanisms of the autoimmune nature of the disease and to focus on diagnosis and treatment. We will review the current literature surrounding this non-pulmonary manifestation of COVID-19 and current treatment options for this uncommon presentation of ITP.

Could SARS-CoV-2 Infection Be a Novel Risk Factor for Multiple Sclerosis?

The outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged the healthcare community worldwide. The SARS-CoV-2 primarily affects the respiratory system; however, strong evidence suggests that SARS-CoV-2 can be neuroinvasive, resulting in several neurological complications. It was previously assumed that some coronaviruses are involved in multiple sclerosis (MS) pathology via various mechanisms. The mechanisms involved in coronavirus-induced central demyelination are complex and largely redundant. Molecular mimicry was proposed to be one of the possible mechanisms. Disruption of the blood-brain barrier, dysregulation in several inflammatory cytokines, and upregulation of matrix metalloproteinases were also thought to induce central demyelinating pathology. This raises a question about the possible role of SARS-CoV-2 as a novel risk factor for MS.