Postinfectious Disorders Research Articles

Quantitative and Computational Spinal Imaging in Neurodegenerative Conditions and Acquired Spinal Disorders: Academic Advances and Clinical Prospects.

Introduction: Quantitative spinal cord imaging has facilitated the objective appraisal of spinal cord pathology in a range of neurological conditions both in the academic and clinical setting. Diverse methodological approaches have been implemented, encompassing a range of morphometric, diffusivity, susceptibility, magnetization transfer, and spectroscopy techniques. Advances have been fueled both by new MRI platforms and acquisition protocols as well as novel analysis pipelines. The quantitative evaluation of specific spinal tracts and grey matter indices has the potential to be used in diagnostic and monitoring applications. The comprehensive characterization of spinal disease burden in pre-symptomatic cohorts, in carriers of specific genetic mutations, and in conditions primarily associated with cerebral disease, has contributed important academic insights. Methods: A narrative review was conducted to examine the clinical and academic role of quantitative spinal cord imaging in a range of neurodegenerative and acquired spinal cord disorders, including hereditary spastic paraparesis, hereditary ataxias, motor neuron diseases, Huntington's disease, and post-infectious or vascular disorders. Results: The clinical utility of specific methods, sample size considerations, academic role of spinal imaging, key radiological findings, and relevant clinical correlates are presented in each disease group. Conclusions: Quantitative spinal cord imaging studies have demonstrated the feasibility to reliably appraise structural, microstructural, diffusivity, and metabolic spinal cord alterations. Despite the notable academic advances, novel acquisition protocols and analysis pipelines are yet to be implemented in the clinical setting.

7820 Immune system adaptation during gender-affirming testosterone treatment

Abstract Disclosure: T. Lakshmikanth: None. C. Consiglio: None. F. Sardh: None. R. Forlin: None. J. Wang: None. Z. Tan: None. H. Barencilla: None. L. Rodriguez: None. J. Sugrue: None. P. Noori: None. M. Ivanchenko: None. L. Piñero Páez: None. L. Gonzalez: None. C. Habimana Mugabo: None. A. Johnsson: None. H. Ryberg: None. Å. Hallgren: None. C. Pou: None. Y. Chen: None. J. Mikeš: None. A. James: None. P.M. Dahlqvist: None. J. Wahlberg Hughes: None. A. Hagelin: None. M. Holmberg: None. M. Degerblad: None. M. Isaksson: None. D. Duffy: None. O. Kampe: None. N. Landegren: None. P. Brodin: None. Immune system adaptation during gender-affirming testosterone treatment Infectious, inflammatory and autoimmune conditions present differently in males and females. Following SARS-CoV-2 infection, male sex is associated with increased risk of death, while female sex is associated with increased risk of the postinfectious disorder, long COVID. Similar trends are seen in other infections. Female immune responses to vaccines are typically stronger, and adverse reactions are more frequent, like most autoimmune diseases. Immunological sex-differences stem from genetic, hormonal and behavioural factors but their relative importance is poorly understood. To understand the consequences of changing sex-hormones in vivo, we performed longitudinal, systems-level analyses in 22 adults, assigned female at birth, and undergoing gender-affirming testosterone treatment (trans-men). We find that sex hormones modulate a cross-regulation axis of type-I interferon (IFN-I) and TNFα in humans. This is mediated by a reduced frequency of plasmacytoid dendritic cells (pDC), and functional attenuation of IFN-I responses in both pDCs and monocytes. Conversely, testosterone potentiates monocyte responses to lipopolysaccharide (LPS) leading to increased TNFα, IL-6 and IL-15 production and downstream epigenetic opening of NFκB regulated genes and potentiation of IFNγ responses, primarily by NK cells. IFNγ in turn feeds back onto monocytes leading to upregulation of SLAMF7 and further enhanced TNFα responses by myeloid cells. These results are corroborated by sex-divergent responses in multiple public datasets and collectively illustrate the dynamic recalibration of human immune systems by sex hormones with implications for individuals undergoing gender-affirming hormone therapy, but also better understanding of divergent responses to infection, vaccines and self-antigens in cisgender individuals. Presentation: 6/2/2024

7820 Immune system adaptation during gender-affirming testosterone treatment

Abstract Disclosure: T. Lakshmikanth: None. C. Consiglio: None. F. Sardh: None. R. Forlin: None. J. Wang: None. Z. Tan: None. H. Barencilla: None. L. Rodriguez: None. J. Sugrue: None. P. Noori: None. M. Ivanchenko: None. L. Piñero Páez: None. L. Gonzalez: None. C. Habimana Mugabo: None. A. Johnsson: None. H. Ryberg: None. Å. Hallgren: None. C. Pou: None. Y. Chen: None. J. Mikeš: None. A. James: None. P.M. Dahlqvist: None. J. Wahlberg Hughes: None. A. Hagelin: None. M. Holmberg: None. M. Degerblad: None. M. Isaksson: None. D. Duffy: None. O. Kampe: None. N. Landegren: None. P. Brodin: None. Infectious, inflammatory and autoimmune conditions present differently in males and females. Following SARS-CoV-2 infection, male sex is associated with increased risk of death, while female sex is associated with increased risk of the postinfectious disorder, long COVID. Similar trends are seen in other infections. Female immune responses to vaccines are typically stronger, and adverse reactions are more frequent, like most autoimmune diseases. Immunological sex-differences stem from genetic, hormonal and behavioural factors but their relative importance is poorly understood. To understand the consequences of changing sex-hormones in vivo, we performed longitudinal, systems-level analyses in 22 adults, assigned female at birth, and undergoing gender-affirming testosterone treatment (trans-men). We find that sex hormones modulate a cross-regulation axis of type-I interferon (IFN-I) and TNFα in humans. This is mediated by a reduced frequency of plasmacytoid dendritic cells (pDC), and functional attenuation of IFN-I responses in both pDCs and monocytes. Conversely, testosterone potentiates monocyte responses to lipopolysaccharide (LPS) leading to increased TNFα, IL-6 and IL-15 production and downstream epigenetic opening of NFκB regulated genes and potentiation of IFNγ responses, primarily by NK cells. IFNγ in turn feeds back onto monocytes leading to upregulation of SLAMF7 and further enhanced TNFα responses by myeloid cells. These results are corroborated by sex-divergent responses in multiple public datasets and collectively illustrate the dynamic recalibration of human immune systems by sex hormones with implications for individuals undergoing gender-affirming hormone therapy, but also better understanding of divergent responses to infection, vaccines and self-antigens in cisgender individuals. Presentation: 6/2/2024

IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a post-infectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. All ten patients included in the study were male, White, with mean age 12.4 years (range 6-16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment.

Somatic, emotional, and gastrointestinal symptom severity are increased among children and adolescents with COVID-19.

Post-infectious disorders of gut-brain interaction (PI-DGBI) have significant impact on children and adolescents. The effect of COVID-19 on PI-DGBI-associated symptoms in this population, however, is unknown. We performed electronic medical record searches to identify patients 8-17 years old with a SARS-CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April-October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms-Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID-19 test or the test result. One hundred and ninety-six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self-reported their child's COVID-19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID-19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID-19 testing that was highest among patients with a positive COVID-19 test. Abdominal pain and diarrhea prior to COVID-19 testing predicted higher NP scores. Among symptomatic COVID-19 tested children, we found increased severity of nausea-associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID-19 test.

Palmitoylethanolamide and Luteolin for Postinfectious Olfactory Disorders: How Clinically Meaningful Is Its Effect?

Introduction: The prevalence of post-viral olfactory dysfunction has increased significantly during the COVID-19 pandemic, posing a major challenge for patients and practitioners. While olfactory training (OT) is a common approach to therapy, there has been increasing interest in supplementing therapy with a combination of palmitoylethanolamide (PEA) and luteolin (LUT), which are known for their anti-inflammatory properties. In this study, their efficacy in the treatment of patients with olfactory loss following upper respiratory tract infections, mainly COVID-19, was investigated in an outpatient clinic. Methods: Fifty patients with persistent olfactory dysfunction were randomized to two groups: one receiving OT and PEA-LUT, the other OT alone. Olfactory function was evaluated before and after treatment. Results: The study group showed significant improvements in odor discrimination and overall olfactory function (TDI score) after treatment with PEA-LUT and OT, while the control group did not. However, when clinically meaningful improvements were considered, there was no significant difference between the groups. Conclusion: The present study suggests that while PEA-LUT may have the potential to improve olfactory function in post-viral dysfunction, the additional benefit over OT alone may be limited. These results contrast with some previous studies.

Critical Care in Guillain–Barré Syndrome

AbstractGuillain–Barré syndrome (GBS) is an autoimmune polyneuropathy characterized by hyporeflexic neuromuscular paralysis and albuminocytologic dissociation in the cerebrospinal fluid. It is a postinfectious disorder. The most common antecedent illnesses are respiratory tract infection and Campylobacter jejuni infection. After the antecedent infection, specific antibodies are generated that cross-react with gangliosides in the host culminating in demyelination of the peripheral nerves or nerve roots. Complement activation also contributes to nerve degeneration. Bilateral symmetrical progression of the limb weakness occurs over a period of a few days followed by a plateau phase, after which a recovery phase follows. Generalized hypotonia and hyporeflexia characterize the limb weakness. Cerebrospinal fluid analysis shows albuminocytologic dissociation. About one-third of patients develop respiratory failure. Neuropathic pain is a disturbing symptom in GBS. Dysautonomia is very characteristic of GBS. Erasmus GBS respiratory insufficiency score predicts the need for mechanical ventilation. The weaning process from mechanical ventilation mainly depends on the recovery of vital capacity and inspiratory force. The definitive treatment for GBS consists of plasma exchange or intravenous immunoglobulin therapy, both of which are equally efficacious. Seasonal variation has been observed in the occurrence and recovery of GBS. Prognosis of GBS varies widely. Erasmus GBS outcome scale scoring system predicts the ability of the patient to walk independently after 6 months. Several GBS cases have been reported globally during recent pandemic of coronavirus disease 2019. Though GBS is a self-limiting disease, there are quite a few research questions that still remain to be answered.

The relationship between infectious agents and juvenile dermatomyositis: a narrative update from the pediatric perspective.

Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy affecting children, being marked by chronic inflammation which mostly impacts on both skin and skeletal muscles; diagnostic criteria of JDM include an unforeseeable mixture of clinical features, while treatment modalities commonly require corticosteroids or immunosuppressant agents. Although the pathogenesis of JDM is not completely understood, several infectious triggers have been linked to its priming via anecdotal reports related to children. Pediatric cases of recent-onset JDM have been temporally associated to an infectious disease by the power of increased titers of circulating antibodies to a putative infectious agent, including parasites, and/or detectable viral RNA or bacterial DNA. With this narrative review we offer an update about JDM association with a host of infections, namely parvovirus B19, Epstein-Barr virus, Coxsackie virus, human immune deficiency virus, severe acute respiratory syndrome coronavirus 2, Mycoplasma pneumoniae and Toxoplasma gondii, as resulting from the medical literature. Few are the evidence-proved results addressing JDM as an unambiguous post-infectious disorder and available data specifically related to children are poor, highlighting the need of further research into the exploration between environmental cut-out factors and JDM.

257. Shared antibody sequences reveal novel public clonotypes of antibodies within and between HIV infected and healthy individuals

Abstract Background Public clonotypes, antibodies against specific antigens in unrelated individuals that have genetic similarities, have been shown in a variety of infections, including SARS-CoV-2 and HIV. These can be exploited as potential diagnostics and to identify past infections that may be related to post-infectious disorders, such as Kawasaki disease, Multiple Sclerosis or Alzheimer's disease. Methods Heavy chain variable sequences were retrieved from public biorepositories (Bioprojects PRJNA486667, PRJNA638224,PRJNA527941) from 270 subjects. These were derived from labeled cohorts: Healthy (116), HIV broadly neutralizing (46), HIV non-broadly-neutralizing (50), HIV-negative (43), and COVID-19 (15). We utilized the Immcantation package of software run on our SUNY Buffalo computational cluster. After PRESTo annotation, duplicate sequences were collapsed and sequences of only single counts were removed. Clonal groups were determined using SCOPer requiring IGHV, IGHJ, and CDR3 amino acid sequence to be perfectly matched. Figures and statistics were generated with immcantation, excel, pandas, and graphpad prism 8. Results There were 5.5 million unique heavy chain sequences from 32 million sequences. Defining public clonotypes as completely sharing CDR3 amino acid sequence and having predicted same germline variable, D, and J chains, 6861 (0.12%) shared clones were found. The distributions of CDR3 lengths showed skewing to shorter CDR3s (mean length of 10.5). There were no stringently defined clones noted in all members. Within HIV infected persons the two most shared clones both used VH1-18, JH4, had CDRaa 8, and were immature IGM/D. Three clones were used in near 10% of cases across both non-HIV and HIV datasets with prominent usage of VH 4 family members and were less mutated and IGM/D. There were eight clones solely shared &amp;gt; 10% within non-HIV/non-Covid infected individuals, with the top shared clones all consistent with matured IGG responses with prominent predicted use of VH3-7 and a number of novel CDR3s noted. Predicted CDR3 length using incantation was compared for cohort of clones that shared predicted V, D, J usage and the exact CDR3 amino acids between individuals. This distribution failed normality testing. Conclusion Identification of public clonotypes will show stochastic bias toward shorter CDR3 regions. There were differences between HIV and non-HIV cohorts and a number of novel public clonotypes were found. Disclosures Mark D. Hicar, MD/PhD, Pfizer: site investigator for 2 trial

Roles of Oxidative Injury and Nitric Oxide System Derangements in Kawasaki Disease Pathogenesis: A Systematic Review.

Kawasaki disease (KD) is an acute febrile vasculitis that occurs mostly in children younger than five years. KD involves multiple intricately connected inflammatory reactions activated by a cytokine cascade. Despite therapeutic advances, coronary artery damage may develop in some patients, who will be at risk of clinical cardiovascular events and even sudden death. The etiology of KD remains unclear; however, it may involve both genetic and environmental factors leading to aberrant inflammatory responses. Given the young age of onset, prenatal or perinatal exposure may be etiologically relevant. Multisystem inflammatory syndrome in children, a post-infectious hyper-inflammatory disorder associated with severe acute respiratory syndrome coronavirus 2, has features that overlap with those of KD. Available evidence indicates that vascular endothelial dysfunction is a critical step in the sequence of events leading to the development of cardiovascular lesions in KD. Oxidative stress and the dysregulation of the nitric oxide (NO) system contribute to the pathogenesis of inflammatory responses related to this disease. This review provides current evidence and concepts highlighting the adverse effects of oxidative injury and NO system derangements on the initiation and progression of KD and potential therapeutic strategies for cardiovascular pathologies in affected children.

COVID-19 and the gastrointestinal tract in children.

This is an overview of the effects of COVID-19 in the gastrointestinal tract in children, and current evidence of the impact of COVID-19 in pediatric patients with chronic gastrointestinal conditions, including inflammatory bowel disease (IBD), chronic liver disease, and disorders of the gut-brain interaction. Children with COVID-19 have a milder course and more favorable outcomes than adults, even in those with immunosuppression due to IBD or liver transplantation. Children with chronic gastrointestinal conditions do not have worse clinical outcomes than healthy children and infection itself has not been linked to an increased incidence of conditions such as IBD and celiac disease, but results regarding post-infectious irritable bowel syndrome are mixed. Research specific to pediatrics is needed, particularly in post-infectious disorders of the gut-brain interaction (PI-DGBIs) and long COVID-19. Data extrapolated from adult trials may not apply to children, as their clinical course is different. PI-DGBIs and long COVID-19 require special attention, as they represent a major morbidity burden in children.

COVID-19 and Risk for Mental Disorders Among Adults in Denmark

Psychiatric outcomes after COVID-19 have been of high concern during the pandemic; however, studies on a nationwide level are lacking. To estimate the risk of mental disorders and use of psychotropic medication among individuals with COVID-19 compared with individuals not tested, individuals with SARS-CoV-2-negative test results, and those hospitalized for non-COVID-19 infections. This nationwide cohort study used Danish registries to identify all individuals who were alive, 18 years or older, and residing in Denmark between January 1 and March 1, 2020 (N = 4 152 792), excluding individuals with a mental disorder history (n = 616 546), with follow-up until December 31, 2021. Results of SARS-CoV-2 polymerase chain reaction (PCR) testing (negative, positive, and never tested) and COVID-19 hospitalization. Risk of new-onset mental disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes F00-F99) and redeemed psychotropic medication (Anatomical Therapeutic Chemical classification codes N05-N06) was estimated through survival analysis using a Cox proportional hazards model, with a hierarchical time-varying exposure, reporting hazard rate ratios (HRR) with 95% CIs. All outcomes were adjusted for age, sex, parental history of mental illness, Charlson Comorbidity Index, educational level, income, and job status. A total of 526 749 individuals had positive test results for SARS-CoV-2 (50.2% men; mean [SD] age, 41.18 [17.06] years), while 3 124 933 had negative test results (50.6% women; mean [SD] age, 49.36 [19.00] years), and 501 110 had no tests performed (54.6% men; mean [SD] age, 60.71 [19.78] years). Follow-up time was 1.83 years for 93.4% of the population. The risk of mental disorders was increased in individuals with positive (HRR, 1.24 [95% CI, 1.17-1.31]) and negative (HRR, 1.42 [95% CI, 1.38-1.46]) test results for SARS-CoV-2 compared with those never tested. Compared with individuals with negative test results, the risk of new-onset mental disorders in SARS-CoV-2-positive individuals was lower in the group aged 18 to 29 years (HRR, 0.75 [95% CI, 0.69-0.81]), whereas individuals 70 years or older had an increased risk (HRR, 1.25 [95% CI, 1.05-1.50]). A similar pattern was seen regarding psychotropic medication use, with a decreased risk in the group aged 18 to 29 years (HRR, 0.81 [95% CI, 0.76-0.85]) and elevated risk in those 70 years or older (HRR, 1.57 [95% CI, 1.45-1.70]). The risk for new-onset mental disorders was substantially elevated in hospitalized patients with COVID-19 compared with the general population (HRR, 2.54 [95% CI, 2.06-3.14]); however, no significant difference in risk was seen when compared with hospitalization for non-COVID-19 respiratory tract infections (HRR, 1.03 [95% CI, 0.82-1.29]). In this Danish nationwide cohort study, overall risk of new-onset mental disorders in SARS-CoV-2-positive individuals did not exceed the risk among individuals with negative test results (except for those aged ≥70 years). However, when hospitalized, patients with COVID-19 had markedly increased risk compared with the general population, but comparable to risk among patients hospitalized for non-COVID-19 infections. Future studies should include even longer follow-up time and preferentially include immunological biomarkers to further investigate the impact of infection severity on postinfectious mental disorder sequelae.

Treatment of Olfactory Disorders After SARS - CoViD 2 Virus Infection.

The benefit of a nasal corticosteroid in the treatment of persistent post-infectious smell disorders is not as clear in previous studies as is assumed for olfactory training. This study would therefore like to describe the treatment strategies using the example of a persistent olfactory dysfunction as a result of a proven infection with SARS-CoViD-2-virus. Twenty patients (average age of 33.9 ± 11.9years) with hyposmia were included in this study from December 2020 to July 2021. Every second patient received additionally a nasal corticosteroid. The two resulting randomized groups of equal size were screened with the TDI test, a 20-item taste powder test for the assessment of retronasal olfaction and otorhinolaryngological examination. The patients were asked to train twice daily using a standardized odor training kit and followed up after 2months and 3months, respectively. We documented a significant overall improvement in olfactory ability over the investigation period in both groups. While the TDI score steadily increased on average under the combination therapy, the rise under olfactory training alone was initially steeper. This short-term interaction effect over mean two months was not statistically significant. According to Cohen, however, a moderate effect (eta2 = 0.055, Cohen`s d = 0.5) can still be assumed. This effect could be explained by a possibly higher compliance at the beginning of the sole olfactory training due to the lack of further drug treatment offers. When the training intensity decreases, the recovery of the sense of smell stagnates. Adjunctive therapy ultimately outweighs this short-term benefit. The results reinforce the recommendation of early and consistent olfactory training on patients with dysosmia due to COVID-19. For continuous improvement of the sense of smell, an accompanying topical treatment seems at least to be worth consideration. The results should be optimized with larger cohorts and using new objective olfactometric methods.

Molecular Targets in Campylobacter Infections

Human campylobacteriosis results from foodborne infections with Campylobacter bacteria such as Campylobacter jejuni and Campylobacter coli, and represents a leading cause of bacterial gastroenteritis worldwide. After consumption of contaminated poultry meat, constituting the major source of pathogenic transfer to humans, infected patients develop abdominal pain and diarrhea. Post-infectious disorders following acute enteritis may occur and affect the nervous system, the joints or the intestines. Immunocompromising comorbidities in infected patients favor bacteremia, leading to vascular inflammation and septicemia. Prevention of human infection is achieved by hygiene measures focusing on the reduction of pathogenic food contamination. Molecular targets for the treatment and prevention of campylobacteriosis include bacterial pathogenicity and virulence factors involved in motility, adhesion, invasion, oxygen detoxification, acid resistance and biofilm formation. This repertoire of intervention measures has recently been completed by drugs dampening the pro-inflammatory immune responses induced by the Campylobacter endotoxin lipo-oligosaccharide. Novel pharmaceutical strategies will combine anti-pathogenic and anti-inflammatory effects to reduce the risk of both anti-microbial resistance and post-infectious sequelae of acute enteritis. Novel strategies and actual trends in the combat of Campylobacter infections are presented in this review, alongside molecular targets applied for prevention and treatment strategies.

Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder

Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.

Частота постинфекционных функциональных нарушений желудочно-кишечного тракта у детей после кампилобактериоза

Кампилобактериоз является одной из наиболее распространенных кишечных инфекций как у взрослых, так и у детей. В нашей стране данные о заболеваемости кампилобактериозом остаются разрозненными и не позволяют в полной мере оценить распространенность данного заболевания. Помимо проблемы высокой заболеваемости детского населения, существует высокий риск развития постинфекционных функциональных гастроинтестинальных расстройств (ПФГИР). Цель исследования. Установить частоту и структуру функциональных гастроинтестинальных расстройств у реконвалесцентов кампилобактериоза. Материалы и методы. В исследование было включено 200 детей, проходивших лечение в специализированном отделении ДНКЦИБ ФМБА России в период 2018–2021 гг. в связи с кампилобактериозом. Осуществлялось клиническое наблюдение за пациентами в условиях стационара с последующим катамнестическим наблюдением в течение 12 месяцев. В процессе наблюдения детей по данным опроса и объективного обследования выявляли постинфекционную ПФГИР. Оценку результатов наблюдения осуществляли с учетом Римских критериев IV пересмотра. Определение предикторов формирования осуществляли с помощью дискриминантного анализа статистического пакета Statistica for Windows. Результаты. Полный срок наблюдения прошли 180 (90%) пациентов. На момент начала катамнестического наблюдения только у 26 (13%) детей имелись жалобы на состояние здоровья: боли в животе при приеме пищи (n=15; 7,5%), метеоризм (n=19; 9,5%), кашицеобразный стул, снижение аппетита (n=5; 2,5%), запоры (n=10; 5,0%). Наиболее часто жалобы со стороны органов пищеварения появлялись в период с 90-го по 180-й дни. Среди симптомов, выявляемых у детей после кампилобактериоза, наиболее часто отмечалось появление периодических болей, дискомфорта в животе (n=64, 32%) и запоров (n=53; 26,5%). В старшей группе диагностированы: синдром раздраженного кишечника (n=19; 51,4%), функциональная диспепсия (n=14; 37,8%) и функциональные запоры (n=4; 10,8%). В младшей возрастной группе диагностированы функциональные запоры (n=18; 60,0%) и функциональная диарея (n=12; 40,0%). Выводы. Проведенное динамическое диспансерное наблюдение за реконвалесцентами кампилобактериоза позволило диагностировать ПФГИР у 67 (33,5%) детей. На основании проведенного исследования была разработана математико-статистическая модель прогнозирования ПФГИР, позволяющая на основании оценки клинических и анамнестических признаков выделить детей, относящихся к группе риска. К предикторам ПФГИР у детей, перенесших кампилобактериоз, вошедшим в модель прогноза, можно отнести: поступление в стационар на поздних сроках болезни с тяжелой степенью кампилобактериоза по шкале Кларка, назначение нескольких курсов антибактериальных препаратов, вынужденный перевод на искусственное вскармливание, возраст, наличие гемоколита, выраженность дегидратации. Campylobacteriosis is one of the most common intestinal infections in both adults and children. In our country, data on the incidence of campylobacteriosis remain scattered and do not fully allow the prevalence of this disease. In addition to the problem of high morbidity in the child population, there is a high risk of developing post-infectious functional gastrointestinal disorders (PFGID). Theaimofthestudy.To establish the frequency and structure of functional gastrointestinal disorders in campylobacteriosis convalescents. Materials and methods. The study included 200 children who were treated in a specialized department of the DNNCIB FMBA of Russia in the period 2018–2021. associated with campylobacteriosis. Clinical observation of patients was carried out in a hospital, followed by follow-up observation for 12 months. In the process of observation of children, according to the survey and objective examination, post-infectious PFGIR was detected. The evaluation of the results of observation was carried out taking into account the Rome criteria of the IV revision. The formation predictors were determined using the discriminant analysis of the statistical package Statistica for Windows. Results. 180 (90%) patients passed the full observation period. At the time of the start of the follow-up observation, only 26 (13%) children had complaints about health conditions: abdominal pain when eating (n=15: 7.5%), flatulence (n=19; 9.5%), mushy stools, loss of appetite (n=5; 2.5%), constipation (n=10; 5.0%). Most often, the appearance of complaints from the digestive organs appeared in the period from 90 to 180 days. Among the symptoms detected in children after campylobacteriosis, the most common were the appearance of periodic pain, abdominal discomfort (n=64, 32%) and constipation (n=53; 26.5%). The older group was diagnosed with: irritable bowel syndrome (n=19; 51.4%), functional dyspepsia (n=14; 37.8%) and functional constipation (n=4; 10.8%). In the younger age group, the following were diagnosed: functional constipation (n=18; 60.0%) and functional diarrhea (n=12; 40.0%). Conclusions. Thus, the dynamic dispensary observation of campylobacteriosis convalescents made it possible to diagnose PFGIR in 67 (33.5%) children. On the basis of the study, a mathematical and statistical model for predicting PFGIR was developed, which allows, based on the assessment of clinical and anamnestic signs, to identify children at risk. The predictors of PFGIR in children who have had campylobacteriosis included in the prognosis model include: admission to the hospital at a late stage of the disease with severe severity of campylobacteriosis on the Clark scale, the appointment of several courses of antibacterial drugs, forced transfer to artificial feeding, age, the presence of hemocolitis, the severity of dehydration.

First report of a patient meeting criteria for both multisystem inflammatory syndrome in children and adult onset Still’s disease

BackgroundCOVID-19 is associated with a postinfectious hyperinflammatory disorder, multisystem inflammatory syndrome in children (MIS-C), that shares characteristics with still’s disease, known as systemic juvenile idiopathic arthritis (SJIA) in children younger than 16, and adult onset Still’s disease (AOSD) in children 16 and older. Both MIS-C and SJIA/AOSD can be complicated by macrophage activation syndrome (MAS), a potentially fatal condition of cytokine storm.Case presentationWe present a 16 year-old male who developed quotidian fever, headache, conjunctival injection, sore throat, nausea and vomiting, diarrhea, rash, and symmetrical polyarticular arthralgia/arthritis 4 weeks after exposure to SARS-CoV-2 and 2 weeks after his first vaccination against COVID-19. Our patient’s laboratory results were significant for elevated inflammatory markers and acute phase reactants. He met criteria for diagnosis with both MIS-C and AOSD. After receiving first-line treatment for both diseases, IVIG and methylprednisolone, our patient improved.ConclusionMAS is a life-threatening rheumatological emergency, and physicians must be able to identify diseases, like MIS-C and AOSD, that may be complicated by MAS. Our patient’s distinguishing feature on presentation was symmetrical polyarticular arthralgia/arthritis, which has not been associated with MIS-C. Simultaneously, AOSD—which is associated with polyarticular arthralgia/arthritis—is only now being recognized as a possible post-infectious entity in the aftermath of COVID-19 infection. In patients like our own, who meet criteria for both MIS-C and AOSD, administering first line treatment for both diseases may be best practice.

Intestinal disorders after acute diarrhea in young children and their coprological predictors

Background. After acute diarrhea in young children, intestinal disturbances and even chronic functional intestinal diseases may occur. To date, no pathogenetically based criteria have been found that would indicate the probability of chronic intestinal disorders, just as the mechanisms of their occurrence after acute diarrhea have not been fully elucidated. The objective: to evaluate the frequency and nature of bowel disorders in children of the younger age group within 6 months after a stay in hospital for acute diarrhea and to establish their relationship with coprological indicators — fecal calprotectin (FCР), the content of carbohydrates (reducing substances, RS), lactic acid (LA) and short-chain fatty acids (SCFA) — acetic, propionic and fatty (butyric). Materials and methods. The study involved 47 children aged 6–24 months who were hospitalized for acute diarrhea. Acute enterocolitis (group I) was diagnosed in 18 patients and was caused by Campylobacter jejuni in 12 cases, Escherichia coli O-18 and Escherichia coli O-44 in 3, Salmonella enteritidis in 2 and Yersinia enterocolitica in one case. Rotaviral gastroenteritis (group II) was diagnosed in 11 patients. Another 11 children had acute symptomatic (parenteral) diarrhea (group III) against the background of intestinal infection — acute otitis, pneumonia, pyelonephritis. In 7 children, diarrhea was classified as functional digestive disorder (group IV). Routine clinical tests were supplemented with an examination of feces for the presence of intestinal parasites, Clostridium difficile A/B toxins, adenoviruses, human hemoglobin, RS, FCP, SCFA and LA. Results. Six-month follow-up established that 14 of 18 children in group I had permanent or temporary loose stools. These complaints in 13 cases were combined with episodes of abdominal pain similar to intestinal colic. The same complaints were much less frequent in children of group II (6 and 3 of 11, respectively), group III (4 and 2 of 11) and group IV (only in 2 of 7 children). The rank correlation analysis did not reveal any significant relationships between the intensity and duration of complaints and FCP, RS, LA, and SCFA in patients of groups I and II. On the contrary, in group III, there were multiple correlations of complaints with FCP, RS, LA, and SCFA. In group IV, the association of loose stools with an increase in LA and acetic acid has been found. Conclusions. According to the 6-month follow-up, 57 % of young children with acute diarrhea complained of loose stools and/or recurrent abdominal pain after discharge from the hospital. Most often, intestinal disorders were detected in children who had acute bacterial enterocolitis. There were no correlations between the intensity of post-infectious (bacterial or viral) disorders with FCP, RS, LA and SCFA during hospitalization. In contrast, such associations were numerous in children with symptomatic (parenteral) and functional diarrhea. It was suggested that the studied coprological parameters can be used to predict the state of the intestine after acute diarrhea.

Chlorogenic acid exerts antibacterial effects by affecting lipid metabolism and scavenging ROS in Streptococcus pyogenes.

Chlorogenic acid (CGA), one of the most abundant polyphenols in the human diet, exhibits many biological properties, including antibacterial properties. Numerous studies have investigated the antibacterial effects of CGA, however, the molecular mechanisms governing its effects against Streptococcus pyogenes have not been fully elucidated. Streptococcus pyogenes is a Gram-positive pathogen that causes a wide range of human infections and postinfectious immune-mediated disorders. In this study, we used an isobaric tagging for relative and absolute quantitation (iTRAQ)-based proteomic technique to investigate the underlying mode of action of CGA against S. pyogenes. KEGG and GO analyses indicated that CGA affected the expression of protein alterations involved in multiple pathways, downregulating the expression of ribosomal proteins, and upregulating the expression of proteins associated with fatty acid metabolism, pyruvate metabolism, and propanoate metabolism, while activating the expression of oxidation-reduction-related proteins. Moreover, further cell-based experiments verified that CGA scavenges intracellular ROS in S. pyogenes. These results suggest that CGA may exert its antibacterial action through several actions, such as downregulating ribosomal subunits, affecting lipid metabolism, and scavenging intracellular ROS. The results of this study may help to elucidate the molecular mechanisms by which CGA combats pathogens.

Multisystem Inflammatory Syndrome in Children (MIS-C)

Purpose of ReviewThe novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic. A unique challenge of this pandemic has been the emergence of multisystem inflammatory syndrome in children (MIS-C), a rare post-infectious hyperinflammatory disorder associated with SARS-CoV-2. This syndrome is characterized by overwhelming systemic inflammation, fever, hypotension, and cardiac dysfunction. This disorder may also have features overlapping with Kawasaki disease (KD), macrophage activation syndrome (MAS), and toxic shock syndrome (TSS). The goal of this review is to outline the presenting features, presumed immunopathogenesis, management, and outcomes of patients with MIS-C.Recent FindingsPatients with MIS-C present with characteristics that fall within a wide clinical spectrum. Main features include fever, gastrointestinal symptoms such as abdominal pain and diarrhea, and cardiac complications such as myocarditis and coronary artery aneurysms, although various other features have been reported. Younger children may present with features of Kawasaki-like disease, and older children are often admitted to the intensive care unit with cardiogenic shock. Current treatment guidelines recommend intravenous immunoglobulins (IVIG) and glucocorticoids, with utilization of biologics in refractory cases. Fortunately, the majority of patients recover, with resolution of the systemic inflammation and cardiac abnormalities. Mortality from MIS-C is rare.SummaryThis review provides an overview of the presenting features, proposed pathogenesis, suggested therapies, and outcomes of MIS-C. Clinicians must have a high clinical suspicion for this disorder in children who have had recent COVID-19 infection or exposure and present with a significant inflammatory response. Understanding of this disorder continues to evolve, and prompt diagnosis and treatment allow for the best possible outcome for patients with MIS-C.