Hyperinflammatory syndrome in a paediatric patient with a recent diagnosis of HIV/AIDS infection: hemophagocytic lymphohistiocytosis or immune reconstitution syndrome?

INTRODUCTION: Haemophagocytic lymphohistiocytosis is a rare and life-threatening condition caused by uncontrolled immune activation leading to excessive inflammation and tissue destruction. It could either be due to a primary genetic defect or be triggered by secondary causes such as infections, autoimmune diseases, rheumatological diseases or post-transplant immunosuppression. We here report the case of a 4-year-old child with a recent AIDS diagnosis who developed a severe systemic inflammation. CASE REPORT: We here report the case of a 4-year-old child with a recent AIDS diagnosis who was admitted to the ER with acute respiratory failure due to Pneumocystis jiroveci infection and Aspergillosis; the following microbiological assessment also showed a CMV, HSV, EBV and HHV-7 coinfection. On the 51st day after she'd started antiretroviral therapy, 39th after she'd followed a course of Bactrim and Caspofungin for PJI and Ambisome for pulmonary Aspergillosis, she started presenting fever, unresponsive to broad-spectrum antibiotic therapy. She also presented worsening of her clinical conditions, with evidence at the laboratory assessments of progressive raise in inflammatory indexes, coagulopathy, trilinear cytopenia and hyperferritinemia. To perform the differential diagnosis between IRIS and HLH, HLA-DR on T cells was studied, turning out negative for IRIS. Therefore, in the suspicion of HLH, a bone marrow aspirate and biopsy were performed with evidence of trilinear cytopenia, prevalence of T-cells and macrophages with signs of phagocytosis. She was started on high-dose steroids and Anakinra for a total of 29 days, resulting in prompt apyrexia and progressive improvement of her clinical conditions and laboratory results. CONCLUSION: To the best of our knowledge there is poor literature available about the differential diagnosis of HLH and IRIS, therefore medical management in the concurrence of these two conditions needs to be further investigated, especially in a setting where immunological testing is not quickly available. The clinical differences between these pathologies are blurred and the bone marrow biopsy within marker for IRIS helped us to distinguish these two entities.

Pediatric COVID-TB: A Clinical Perspective Based on the Analysis of Three Cases.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are currently two major causes of death among infectious diseases. Active tuberculosis and a history of tuberculosis appear to be associated with an increased risk of COVID-19. This coinfection, named COVID-TB, was never described in previously healthy children. We report three cases of pediatric COVID-TB. We describe three girls affected by tuberculosis, who tested positive for SARS-CoV-2. The first patient is a 5-year-old girl who was hospitalized for recurrent TB lymphadenopathy. As she never had any complications related to the concomitant infection with SARS-CoV-2, she received TB treatment. The second case is a 13-year-old patient with a history of pulmonary and splenic tuberculosis. She was admitted to the hospital due to deteriorating respiratory dynamics. She was already undergoing treatment for TB, but in the absence of improvement, she also required treatment for COVID-19. Slowly, the general condition improved until discharge. The last patient, a 10-year-old girl, was hospitalized for supraclavicular swelling. The investigations showed disseminated TB characterized by lung and bone involvement without COVID-19-related complications. She was treated with antitubercular and supportive therapy. Based on the data obtained from the adult population and our small experience, a pediatric patient with COVID-TB infection should be considered potentially at risk of worse clinical outcomes; for this reason, we suggest close observation, careful clinical management, and consideration of targeted anti-SARS-CoV-2 therapies.

Case report: A new pathogenic variant of LRBA deficiency with a complex phenotype and Rosai-Dorfman disease.

We reported a new pathogenic variant of LRBA deficiency with a complex phenotype-neonatal diabetes, very early-onset inflammatory bowel disease, and polyarthritis-who presented with lymph node enlargement. A case of Rosai-Dorfman's disease (RDD) was confirmed. The occurrence of an RDD lesion in LRBA-deficiency has never been reported so far.

Host Defenses to Viruses: Lessons from Inborn Errors of Immunity.

The constant battle between viruses and their hosts leads to their reciprocal evolution. Viruses regularly develop survival strategies against host immunity, while their ability to replicate and disseminate is countered by the antiviral defense mechanisms that host mount. Although most viral infections are generally controlled by the host's immune system, some viruses do cause overt damage to the host. The outcome can vary widely depending on the properties of the infecting virus and the circumstances of infection but also depends on several factors controlled by the host, including host genetic susceptibility to viral infections. In this narrative review, we provide a brief overview of host immunity to viruses and immune-evasion strategies developed by viruses. Moreover, we focus on inborn errors of immunity, these being considered a model for studying host response mechanisms to viruses. We finally report exemplary inborn errors of both the innate and adaptive immune systems that highlight the role of proteins involved in the control of viral infections.

COVID-19-Related Anosmia: The Olfactory Pathway Hypothesis and Early Intervention.

Anosmia is a well-described symptom of Corona Virus Disease 2019 (COVID-19). Several respiratory viruses are able to cause post-viral olfactory dysfunction, suggesting a sensorineural damage. Since the olfactory bulb is considered an immunological organ contributing to prevent the invasion of viruses, it could have a role in host defense. The inflammatory products locally released in COVID-19, leading to a local damage and causing olfactory loss, simultaneously may interfere with the viral spread into the central nervous system. In this context, olfactory receptors could play a role as an alternative way of SARS-CoV-2 entry into cells locally, in the central nervous system, and systemically. Differences in olfactory bulb due to sex and age may contribute to clarify the different susceptibility to infection and understand the role of age in transmission and disease severity. Finally, evaluation of the degree of functional impairment (grading), central/peripheral anosmia (localization), and the temporal course (evolution) may be useful tools to counteract COVID-19.

Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.

OBJECTIVE: Persistent inflammation and higher risk to develop cardiovascular diseases still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART. DESIGN: Cross-sectional study including 61 ART-treated PHIV (age range 3-30 years old) and 71 age-matched healthy controls. Blood and stool sample were collected at the same time and analyzed for gut microbiota composition and plasma biomarkers. METHODS: Gut microbiota composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, inflammation and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4 and CD8T cells. RESULTS: We identified two distinct gut microbiota profiles (groups A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila, whereas gut microbiota of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of soluble E-selectine (P = 0.0296), intercellular adhesion molecule-1 (P = 0.0028), vascular adhesion molecule-1 (P = 0.0230), IL-6 (P = 0.0247) and soluble CD14 (P = 0.0142) in group A compared with group B. CONCLUSION: Distinctive gut microbiota profiles are differently associated with inflammation, microbial translocation and VEA. Future studies are needed to understand the role of A. muciniphila and risk to develop cardiovascular diseases in PHIV.