Post-infectious Disease Research Articles

Single Center-Based Real-World Experience on Anti-IL 1 Biological Response Modifiers: A Case Series and Literature Review.

This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children.

Molecular mimicry in multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection1,2, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of samples from patients with MIS-C to identify a distinct set of host proteins targeted by patient autoantibodies including a particular autoreactive epitope within SNX8, a protein involved in regulating an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed antibody responses from patients with MIS-C to the complete SARS-CoV-2 proteome and found enriched reactivity against a distinct domain of the SARS-CoV-2 nucleocapsid protein. The immunogenic regions of the viral nucleocapsid and host SNX8 proteins bear remarkable sequence similarity. Consequently, we found that many children with anti-SNX8 autoantibodies also have cross-reactive T cells engaging both the SNX8 and the SARS-CoV-2 nucleocapsid protein epitopes. Together, these findings suggest that patients with MIS-C develop a characteristic immune response to the SARS-CoV-2 nucleocapsid protein that is associated with cross-reactivity to the self-protein SNX8, demonstrating a mechanistic link between the infection and the inflammatory syndrome, with implications for better understanding a range of post-infectious autoinflammatory diseases.

Complex rehabilitation program for children, suffering for hypertensive vegetative-vascular dystonia and its efficiency estimation

The prevalence of vegetative-vascular (neuro-circulatory) dystonia of the hypertensive type in children has recently been observed. The so-called constitutional type of VVD can occur under hormonal changes; it also could be caused by central nervous system serious disorders, due to post-infectious diseases as well as addiction to alcohol and tonic drinks. The signs of VVD in adults and children are practically the same. The predominant symptom is vasoconstriction, whereby the body reacts with an increase in blood pressure. The aim of the study is to develop a set of rehabilitation methods using health aerobics classes for children aged 14–16 with hypertensive vegetative-vascular dystonia and to evaluate the effectiveness of a comprehensive physical rehabilitation program. The study involved 21 adolescent children. In the course of study there were applied empirical, sociological, clinical, instrumental and mathematical statistics research methods, that contributed to solving the problem through the development of an integrated program of physical rehabilitation for children aged 14–16 with hypertensive vegetative-vascular dystonia using recreational aerobics. There was also studied the effect of this program on the cardiorespiratory system and physical performance on the basis of the results obtained. Outcomes. The results of the study made it possible to ascertain that children who underwent a rehabilitation course in accordance with the program developed, recorded significant positive changes in the cardiorespiratory system, which was determined in terms of heart rate and blood pressure measurement, and the general adaptive capacity of the body, which was estimated using the Rufier functional test and step test.

Chimeric hepatitis B surface antigen virus-like particles expressing the strep A epitope p*17 elicit a humoral immune response in mice

To optimize immunogenicity, bacterial epitopes in putative vaccine constructs can be presented to immune cells as multiple repeated structures on a defined nanoparticle. Virus-like particles (VLPs) are viral capsid proteins that self-assemble to form compact and highly ordered nanoparticles that are within the optimal size range for uptake by dendritic cells. VLPs mimic the live virus in size and form but contain no viral genetic material, are therefore noninfective and are the basis of safe and effective vaccines against hepatitis B virus (HBV) and human papillomavirus (HPV). Due to their particulate nature, molecular stability, and expression of high density and repetitive antigen displays, recombinant cell culture-derived VLPs are ideal platforms for the delivery of small molecules, including bacterial epitopes. We developed a putative vaccine by expressing a minimal epitope from the bacterium Streptococcus pyogenes (Strep A) on the surface of a recombinant VLP comprising multiple copies of HBV small envelope protein (HBsAg-S). Strep A is responsible for a wide spectrum of human infections and postinfectious diseases that disproportionately affect children and young adults living in resource-poor communities. No vaccine is currently available to offer sufficiently broad protection from the numerous and diverse strains of Strep A endemic in these at-risk populations. The Strep A antigen targeted by our vaccine construct is p*17, a cryptic epitope from a highly conserved region of the Strep A M-protein with demonstrated enhanced immunogenicity and broad protective potential against Strep A. To ensure surface expression and optimal immunogenicity, we expressed p*17 within the immunodominant “a” determinant of HBsAg-S. The recombinant VLPs (VLP-p*17) expressed in HEK293T cells spontaneously formed 22 nm particles and induced the production of high titers of p*17-specific IgG in BALB/c mice immunized with three 0.5 μg doses of VLP-p*17 formulated with adjuvant.

Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults.

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.

Muscle abnormalities worsen after post-exertional malaise in long COVID

A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

Guillain – Barre syndrome associated with Helicobacter pylori isolates from rectal swabs of Four Patients: University of Benin Teaching Hospital Experience

Background: A Gram-negative bacteria known as Helicobacter pylori (H. pylori) is thought to be the cause of autoimmune gastrointestinal diseases. Additionally, this pathogen has been connected to peripheral neuropathies and extra-gastrointestinal illnesses with autoimmune sequelae. H. pylori may be involved in the 30% of GBS cases that Campylobacter jejuni is blamed for. Guillain-Barré syndrome (GBS) typically has a post-infectious aetiology. The Aim of the study is to show that rectal swabs to isolate Helicobacter pylori as a cause of Guillain - Barre syndrome should be a routine instead of gastric biopsy. Methods: The study was a Retrospective Cross Sectional Study. It involved a review of Case notes of Patients that were admitted in the Neurology Unit of UBTH from 2014-2019, been managed for Guillain-Barre syndrome associated with H. pylori infection and also a review of their Medical microbiology laboratory test records during management especially their rectal swab Microscopy, Culture and Sensitivity results. It has never been the practice of the Neurology unit to do rectal swabs for patients with Guillain - Barre syndrome, this was done by the medical microbiology unit that co-managed the patient. Patients with incomplete or missing medical data were excluded from the study. Results: Four case series of one male and three female patients, age ranged from 7 years to 23years with the mean age of 15 ± 8 years. The most common initial symptom was weakness in the extremities which was seen in all the patients. Motor deficit involved all four limbs in all the patients. The mode of onset was progressive in all the cases and ascending. History of peptic ulcer disease was present in all four patient and H. pylori was isolated from rectal swabs from all the patients. Three (75%) of the patient showed marked improvement on commencement of Omeprazole and erythromycin, while one (25%) ,did well on amoxicillin and Omeprazole. One (25%) had complications of bilateral patchy lower limb skin exfoliation and desquamation. A case of death was recorded. On discharge complete functional recovery was noted in two (50%), while one (33%) had partial recovery. Conclusion: This study of four case series highlights a relatively inexpensive and straightforward faecal specimen collection by rectal swab, and readily available faecal specimen compared with gastric biopsy specimen, in the laboratory diagnosis and isolation of Helicobacter pylori, a cause (among other causes) of Guillain-Barre Syndrome, which is a medical emergency in most cases.In addition Guillain-Barre Syndrome linked with H. pylori is not always a Post-infectious diseases because medications used to clear the gastrointestinal tract of Bacterial usually lead to recovery from the paralysis caused by Guillain-Barre Syndrome.

First insights into multidisciplinary and multispecialty long COVID networks-a SWOT analysis from the perspective of ambulatory health care professionals.

Multidisciplinary and multispecialty approaches with central integration of primary care, individualized long-term rehabilitative care, and multidisciplinary care pathways are recommended by international consortia to face the challenges of care of long COVID. Two regional long COVID networks-Rhein-Neckar (RN) and Ludwigsburg (LU) have emerged as ad hoc examples of best practice in Southern Germany. The aim of the community case study is to provide first insights into the experiences of the networks. The exploratory observational study was conducted between April and June 2023, focusing on an observation period of just under 24 months and using a document analysis supported by MAXQDA and SWOT analysis with ambulatory health care professionals in two online group discussions. The document analysis revealed that both networks have defined network participants who have agreed on common goals and patient pathways and have established ways of communicating, organizing, and collaborating. Both networks agreed on a primary care-based, multidisciplinary and multispecialty approach. The main differences in realization emerged in LU as a focus on the ambulatory setting and very concrete application to individual patients, while RN showed a focus on an intersectoral character with participation of the specialized university hospital sector, knowledge transfer and a supra-regional approach with the involvement of the meso and macro level. The SWOT analysis (n = 14 participants, n = 6 male, 7 physicians (4 disciplines), 7 therapists (5 professions)) showed strengths such as resulting collaboration, contribution to knowledge transfer, and improvement of care for individual patients. As barriers, e.g., lack of reimbursement, high efforts of care, and persistent motivation gaps became apparent. Potentials mentioned were, e.g., transferability to other diseases such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, promotion of addressing a "difficult topic" and promotion of intersectoral care concepts; risks mentioned were, e.g., limited network resources and negative effects on the development of other structures. Resulting implications for practice and research address a call to policy makers and funders to support further research to find out what generalizable results regarding usefulness, effectiveness, and efficiency including transferability to other post-infectious diseases can be derived.

Chronic overlapping pain conditions increase the risk of long COVID features, regardless of acute COVID status.

Chronic overlapping pain conditions (COPCs) refer to conditions that have similar central nervous system pathophysiologic mechanisms driving widespread pain as well as common comorbid symptoms such as fatigue and problems with sleep, memory, and mood. If COPCs predict the onset of long COVID, this could offer a valuable orientation for long COVID-related research and clinical care. This retrospective cohort study aimed to determine whether having a COPC predicts the onset of long COVID features using US electronic health records and 1:1 propensity score matching without replacement. The study cohorts included (1) people with acute COVID (n = 1,038,402), (2) people with acute influenza (n = 262,092), and (3) a noninfected cohort comprising people with a routine healthcare encounter (n = 1,081,593). Having a COPC increased the risk of long COVID features in all 3 study cohorts. Among those with COVID, having a pre-existing COPC increased the risk by 1.47 (95% CI = 1.46, 1.47). In the influenza cohort, COPCs increased the risk by 1.39 (95% CI = 1.38, 1.40). In the noninfected cohort, COPCs increased the risk by 1.57 (95% CI = 1.56, 1.59). These findings reinforce the likelihood that nociplastic mechanisms play a prominent role in long COVID. Recognizing that this ubiquitous nonspecific syndrome occurs frequently in the population can inform precision medicine therapies that avoid the pitfalls of viewing long COVID exclusively in the framework of postinfectious disease.

Nutritional status of elderly patients previously ill with COVID-19: Assessment with nutritional risk screening 2002 (NRS-2002) and mini nutritional assessment (MNA-sf)

BackgroundLong-term effects of COVID-19 showed a wide range of symptoms. Also, it was found that older patients were five times more likely than younger patients to develop long-COVID symptoms (1). This study aimed to investigate the use of Nutrition Risk Screening 2002 (NRS-2002) and the Mini Nutrition Assessment–Short Form (MNA-sf) among COVID-19 in elderly patients in Saudi Arabia. MethodsA total of (n = 159) COVID-19 elderly patients were recruited in the study; the relationship between patients' characteristics, including age, gender, Body Mass Index (BMI), infection history, vaccination and chronic disease were evaluated using NRS-2002 and MNA-sf. Multivariate logistic regression to estimate the Odd Ratio (OR) by comparing the OR of different variables between normal nutritional Status and at-risk and Cohen's kappa (κ) coefficient was assessed to analyse the agreement between both tools. ResultsMNA-sf showed a positive association between age and malnutrition risk ≥ 66 years old P = 0.035. Both tools showed a negative association between BMI (P < 0.001 and P = 0.046), respectively and vaccination (P = 0.002 and P = 0.01), respectively, with risk for malnutrition. There was no significant association between Diabetes (DM) and malnutrition risk, but elderly Cardiovascular Disease (CVD) were at malnutrition risk using the NRS- 2002 tool P = 0.003. Inversely, people infected six months or more before malnutrition assessment have a lower risk of malnutrition P = 0.05. ConclusionsBoth tools were valuable and practical tools for screening elderly people with COVID-19 who are at nutritional risk and those in need of additional nutritional intervention. Further research needed to be applied in the relationship between nutritional status during and post-infectious disease for elderly people using cross-sectional and intervention studies in order to prevent malnutrition complications in Saudi Arabia.

COVID-19 Immunization Rates in Patients with Inflammatory Bowel Disease Worldwide: A Systematic Review and Meta-Analysis.

Individuals with Inflammatory Bowel Disease (IBD) are characterized by an increased vulnerability to complications stemming from infectious diseases. While these patients do not inherently face a heightened risk of SARS-CoV-2 infection compared to the general population, their vulnerability to severe COVID-19 complications and subsequent hospitalization is notably increased. The objective of our study is to quantitatively assess the global coverage of COVID-19 vaccination among individuals with IBD, achieved through a comprehensive meta-analysis and systematic review. Thirteen studies were systematically selected from scientific articles available in the MEDLINE/PubMed, ISI Web of Knowledge, and Scopus databases, spanning from 1 January 2021 to 25 July 2023. The pooled prevalence of COVID-19 vaccine uptake was estimated at 72% (95%CI = 59-83%) for at least one dose, 81% (95%CI = 68-91%) for the complete vaccination regimen, and 71% (95%CI = 46-91%) for the third dose. Analysis of the determinants influencing vaccination uptake revealed several significant associations. These encompassed Caucasian ethnicity, female sex, absence of immunosuppressive therapy, advanced age, prior receipt of the anti-influenza vaccine, absence of a history of COVID-19 infection, and the provision of advice from gastroenterologists, all linked to improved compliance. Our study underscores a noteworthy yet not entirely optimal COVID-19 vaccination coverage among individuals with IBD. A multifaceted approach is warranted to enhance vaccination rates. Within this context, the role of gastroenterologists extends beyond direct patient care, encompassing a pivotal responsibility in preventing complications stemming from post-infectious diseases.

Body mass index and fitness in late adolescence and risk of cardiovascular disease, respiratory disease, and overall death after COVID-19.

Since obesity and poor fitness appear to be unfavorable for both cardiovascular health and coping with viral infections such as COVID-19, they are of specific interest in light of the increased risk of cardiovascular and respiratory events now seen after infection with SARS-CoV-2. Therefore, the aim of the present study was to investigate how body mass index (BMI) and cardiorespiratory fitness (CRF) in late adolescence are associated with the risk of cardiovascular disease (CVD), respiratory disease, and mortality after COVID-19. In this study, 1.5 million 18-year-old Swedish men with BMI and CRF measured during enlistment for military service 1968-2005 were included. Hospitalized and non-hospitalized COVID-19 cases were identified through the Patient Register or positive polymerase chain reaction tests, and age-matched with non-infected controls. CVD, respiratory disease, and mortality after COVID-19 were divided into <60days, 60-180days, >180days post-infection. Cox regression models were used. Hospitalized COVID-19 cases (n=9839), compared to controls, had >10-fold, 50 to 70-fold, and >70-fold hazards of CVD, respiratory disease, and mortality over the initial 60days post-infection with little variation across BMI or CRF categories. The elevated risks persisted at declining levels >180days. For non-hospitalized COVID-19 cases (n=181,822), there was a 4- to 7-fold increased acute mortality risk, and high CRF was associated with lower risk of post-infectious respiratory disease. The high hazards of adverse outcomes during the first two months after COVID-19 hospitalization, and across BMI and CRF categories, declined rapidly but were still elevated after six months. Adolescent CRF was associated with respiratory disease after COVID-19 without hospitalization, which gives further support to the health benefits of physical activity.

Reality of drug-induced erythema multiforme: A French pharmacovigilance study

Since the 2002 SCAR study, erythema multiforme (EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). To describe EM reported in the FPDB and to compare the quality and the characteristics of the reports. This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. Among 182 selected reports, 140 (77%) were analyzed. Of these, 67 (48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36 (49%) had a probable non-drug cause and 28 (38%) were associated with only drugs with an onset time ≤4 days and/or ≥29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Etiological work-up was more often performed in period 2 than 1 (53.1% vs 29.3%, P=0.04), and the time to onset from 5 to 28 days was more frequent in period 2 (59.2% vs 40%, P=0.04). This study suggests that possible drug-induced EM is rare. Many reports describe "polymorphic" rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

A Rare Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis in an Infant Presenting with Regression and Movement Disorder.

A Rare Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis in an Infant Presenting with Regression and Movement Disorder.

Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity.

New drugs that precisely target the immune mechanisms critical for cytotoxic T lymphocyte (CTL) and natural killer (NK) cell driven pathologies are desperately needed. In this perspective, we explore the cytolytic protein perforin as a target for therapeutic intervention. Perforin plays an indispensable role in CTL/NK killing and controls a range of immune pathologies, while being encoded by a single copy gene with no redundancy of function. An immunosuppressant targeting this protein would provide the first-ever therapy focused specifically on one of the principal cell death pathways contributing to allotransplant rejection and underpinning multiple autoimmune and postinfectious diseases. No drugs that selectively block perforin-dependent cell death are currently in clinical use, so this perspective will review published novel small molecule inhibitors, concluding with in vivo proof-of-concept experiments performed in mouse models of perforin-mediated immune pathologies that provide a potential pathway toward a clinically useful therapeutic agent.

Balchaturbhadra Churna as a potential medicine for SARS-CoV2 infection in pediatric setting

Abstract Background: Balachaturbhadra Churna (BC), Ayurvedic powder dosage form, has four ingredients (Aconitum heterophyllum Wall. Ex Royle, Pistacia integerrima stew. Ex brandis, Piper longum Linn., and Cyperus rotundus linn.), which is commonly prescribed for treating fever, cough, and diarrhea in a pediatric setting. Aim: The present study evaluates the possible antiviral effect of phytochemicals from the ingredients of BC on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (MPro), Ribose Nucleic Acid (RNA) dependent RNA polymerase (RdRP), and spike-angiotensin-converting enzyme 2 (SA) complex through in silico evaluation. Materials and methods: X-ray crystal structure of MPro and Spike-Ace (SA) complex with Protein Data Bank (PDB) IDs 6LU7 and 6LZG and the SWISS model of RdRP were used as the drug targets. An enhanced docking methodology has been implemented to perform the molecular docking of these phytochemicals against the above-mentioned drug targets of SARS-CoV-2. DOCK6 was used to perform the docking of these phytochemicals. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug likeliness properties for these selected phytochemicals were performed using SWISS ADME. Results: The ensemble docking studies suggest that aconitine, lappaaconitine from Aconitum heterophyllum Wall. Ex Royle, 2’-hydroxyisorientin from Pistacia integerrima stew. Ex brandis, and guineesine, pipercide and piperoic acid from Piper longum Linn. hold the potential to bind favorably with the SARS-CoV-2 drug targets. The drug-likeliness and ADMET properties were calculated for these phytochemicals indicating that all three phytochemicals from Piper longum were observed to have considerate drug-likeliness and ADMET properties. Aconitine has a molecular weight slightly higher than 500 kDA and has more than 10 hydrogen bond acceptors. Conclusion: The in silico study demonstrates that phytochemicals present in BC viz., aconitine, lappaaconitine from Aconitum heterophyllum, 2’-hydroxyisorientin from Pistacia intergerrima and guineesine, pipercide, and piperoic acid from Piper longum hold the potential to bind favourably with the SARS-CoV-2 drug targets. The study also provides evidence for drug likeliness and ADMET properties for these phytochemicals suggesting that BC can be further studied as a potential drug of choice for treating SARS-CoV-2 infection to avert post-infectious disease, characterized by multisystem inflammatory syndrome in children in rare cases and other similar conditions in the pediatric setting.

Two pediatric cases of multisystem inflammatory-like syndrome following COVID-19 vaccination

Multisystem inflammatory syndrome in children (MIS-C) is a novel post-infectious disease occurring in the context of SARS-CoV2 infection. COVID-19 vaccines have been authorized since December 2020, and adverse events including myocarditis have been reported following vaccination. We describe the cases of two pediatric patients presenting with clinical and laboratory features suggestive of MIS-C a few days after receiving their first dose of the Pfizer BNT162b2 vaccine. The outcome was favorable for both patients (after corticosteroid and immunoglobulin administration for one patient). These cases suggest an association between the COVID-19 vaccine and the occurrence of MIS-C.

The Role of Infection and Inflammation in the Pathogenesis of Pediatric Arterial Ischemic Stroke

Infections play an important role in the pathogenesis of acute ischemic stroke (AIS) in neonates and children. In neonates, chorioamnionitis or intrauterine inflammation has been implicated as a common risk factor for AIS. In infants and children, recent investigations demonstrated that even minor childhood infections are associated with subsequent increased risk for AIS. Post-infectious inflammatory mechanisms following infections with herpesviruses may lead to focal cerebral arteriopathy (FCA), one of the most common causes of AIS in a previously healthy child. Other agents such as parvovirus B19, dengue virus, and SARS-CoV-2 have recently been implicated as other potential triggers. Infections are compelling treatable stroke risk factors, with available therapies for both pathogens and downstream inflammatory effects. However, infections are common in childhood, while stroke is uncommon. The ongoing VIPS II (Vascular effects of Infection in Pediatric Stroke) study aims to identify the array of pathogens that may lead to childhood AIS and whether either unusual strains or unusual combinations of pathogens explain this paradox. Immune modulation with corticosteroids for FCA is another active area of research, with European and U.S. trials launching soon. The results of these new pediatric stroke studies combined with findings emerging from the larger field of immune-mediated post-infectious diseases will likely lead to new approaches to the prevention and treatment of pediatric stroke. This review highlights recent developments from both clinical and animal model research enhancing our understanding of this relationship between infection, inflammation, and stroke in neonates and children.

D2/D3 Receptor Agonism: Paving the Way for a New Therapeutic Target for Taste Disorders in Parkinson's Disease and Other Conditions?

Chemosensory (i.e., olfaction and taste) dysfunction is common in neurodegenerative (e.g., Parkinson's disease, Alzheimer's disease, and dementia), psychiatric (e.g., depression, bipolar disorders, other conditions), and postinfectious (i.e., long COVID) diseases and in the elderly. Despite its impact on patients' quality of life, no established treatment for taste disorders exists so far. A recent report on the effect of pramipexole, a D2/D3 agonist, on taste performance in healthy participants provides support for a new potential therapeutic target for taste dysfunction to be tested in future randomized, placebo-controlled, clinical trials across several populations reporting gustatory symptoms.

NeuroCOVID-19: a critical review.

The COVID-19 pandemic has challenged neurologists since its early days. Neurology consultation services were then overloaded by emergency department and intensive-care patients with acute neurological syndromes. These complications are better explained today, but the growing number of patients with reported longstanding neurological symptoms constitute an emerging, complex, and still poorly understood phenomenon. This review summarizes data on relevant neurological manifestations of acute SARS-CoV-2 infection and lasting post-infectious disease, also known as Long COVID. The complex history of Long COVID is examined to illustrate the upsides and challenges imposed by the active participation of patient communities in the production of medical knowledge. Narrative review. Infection with the severe acute respiratory syndrome coronavirus 2 is associated with encephalopathy/delirium, cerebrovascular disease, headache, and peripheral nervous system involvement. Long COVID is a living concept jointly defined by patient communities, physicians and scientists, including neurologists. Co-production of Long COVID knowledge between scientists and patients has initiated an era of patient-led research and evidence-based activism that acts as a two-edged sword - putting patient's suffering in the spotlight, but with a tradeoff in methodological consistency.