Unique presentations of the post COVID-19 infection, multisystem inflammatory syndrome in children.

Introduction: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19, continuous to affect most of the world's population. In children, the respiratory and systemic involvement appears to have a much more benign course in comparison to adults, with almost no fatalities reported. However, we are encountering a post-infectious immune mediated condition, termed, multisystem inflammatory syndrome in children (MIS-C). In most cases the main features are prolonged fever and elevation of inflammatory markers, many of the patients present with abdominal pain and varying degree of myocardial involvement from mild reduction in cardiac output to the most alarming manifestation of cardiovascular shock. Results: We present two patients with unusual manifestations of MIS-C, related to post COVID-19 infection, an infant born to a mother who was severely ill at the very end of pregnancy, presenting with prolonged fever, rash, pericardial effusion, and evidence of coronary arteries wall thickening as a result of inflammation, and, a teenage girl with severe cardiac tamponade without the more common cardiac manifestations of myocardial involvement. Discussion: Post COVID-19 MIS-C can present in a wide variety of manifestations. The pathophysiologic mechanism underlying these inflammatory responses in infants are yet to be elucidated. Physicians should be aware of such presentations since rapid diagnosis and treatment are key for favorable outcome.

A case of Common Variable Immune Deficiency with Lung disease- Not Just Bronchiectasis

Introduction: Common Variable Immune Deficiency (CVID) is the most prevalent form of severe antibody deficiency in children and in adults. Most patients have recurrent infections, mainly sinopulmonary infections. Despite adequate IVIG replacement therapy chronic lung disease continues to be a main cause of morbidity and mortality. The term granulomatous-lymphocytic interstitial lung disease (GLILD) is frequently used to described the Interstitial lung disease associated with immune dysregulation in primary antibody deficiency such as CVID. Aim: To describe a 10-year-old boy with CVID who developed GLILD and his response to treatment with Rituximab. Discussion: Although GLILD is a well described condition that accompanies CVID as a manifestation of immune dysregulation, it is still under recognized, especially in the pediatric population. Among experts, there is little uniformity when it comes to diagnostic and treatment approaches. Recent studies showed improved outcomes when using combination therapy with Rituximab, such as in our case presentation. Statement of Novelty: This report discusses a case of CVID in a 10-year-old boy, with no genetic diagnosis, whose lung functions and general condition continued to deteriorate despite adequate IGRT and MMF treatment. After the diagnosis of GLILD we initiated treatment with a 4-dose weekly course of Rituximab with prompt resolution of his interstitial disease. In our case we shed light on GLILD, an important condition that accompanies CVID and demonstrate an excellent response to Rituximab-a steroid sparing agent, which is a crucial aspect when considering therapeutic choices for the pediatric population.

Elevated serum gamma globulins in apparently healthy Nigerians living in Ogbomoso: A possible manifestation of phagocytic dysfunction

Background: Serum protein electrophoresis abnormalities, particularly elevated gamma globulins (hypergammaglobulinemia), have been reported in apparently healthy Nigerians living in Ogbomoso and elsewhere. Since the mechanisms for this phenomenon have not been fully substantiated, we hypothesized that impaired neutrophil phagocytosis could contribute to this condition. Methods: Healthy humans exhibiting hypergammaglobulinemia (HGG) were identified using serum protein electrophoresis (SPE) performed on cellulose acetate gel in barbital buffer (pH 8.6). GelQuant image analysis and quantitation software were further employed to quantify gamma globulin fraction. Neutrophils were isolated from K3EDTA anticoagulated peripheral blood using neutrophil isolation histopaque of Kayman Chemical, USA. Neutrophil phagocytic activity was analyzed using a non-subjective commercial colorimetric phagocytosis assay kit obtained from Cell-Biolab Inc, USA. Results: The purity and viability of isolated neutrophils were approximately 94 % and 92 %, respectively. Ex-vivo phagocytic activity of neutrophils isolated from apparently healthy subjects exhibiting HGG, expressed in absorbance unit (AU), was 48.1±8.6 % which was significantly lower (p<0.05); compared to the controls (98.9±14.3 %). Conclusion: Since neutrophils play crucial roles in innate immune responses, impairment of neutrophil phagocytic activity may lead to persistent antigenic stimulations of the adaptive immune system. This could in turn orchestrate γ-globulins expression leading to HGG. Statement of novelty: We demonstrated a reduced neutrophil phagocytic activity as a possible basis for hypergammaglobulinemia in healthy Nigerians, perhaps for the first time.

Children should be offered vaccination against COVID-19

Since the start of the COVID-19 pandemic, there has been conflicting evidence on SARS-CoV-2 infection and transmission in children. Early studies reported only anecdotal outbreaks in school settings and low case numbers in children, driving speculation that the virus may not be as easily spread in this age group. However, these reports are unlikely to have represented the true frequency of infections, given the widespread school closures implemented to cut transmission opportunities and limitations of swab testing in children (lower uptake, swab volumes) resulting in missed cases. Indeed, subsequent studies measuring viral load in children reveal similar levels and trajectories as adults, indicating that children can readily transmit the virus and can accelerate infections throughout communities. In the midst of a fourth COVID-19 wave and a resurgence of cases in Canada, the majority with the highly transmissible and virulent B.1.617.2 (delta) variant, we discuss the pressing need for vaccination of children.

Wiskott Aldrich syndrome caused by a novel mutation in WASP gene presenting with a mild phenotype

Background: Wiskott–Aldrich syndrome (WAS) is X-linked recessive disorder associated with combined immunodeficiency, microthrombocytopenia, eczema, and an increased risk of autoimmunity and cancer. Aim: To report the clinical presentation, immune features, and genetic mutation in a patient with a novel mutation in the WASP gene causing a mild phenotype of Wiskott Aldrich syndrome Methods: Patient’s chart was reviewed. We report the phenotypical and laboratory characteristics of a patient with a mild phenotype of Wiskott Aldrich syndrome with a novel mutation found by WASP gene sequence analysis. Results: This patient presented with thrombocytopenia and 3 episodes of otitis media at 24 months of age, with no other significant manifestations suggestive of immunodeficiency or immune dysregulation. A missense mutation was found in exon 12 of WASP gene, C1498>T, leading to a Trp500Arg amino acid change. Currently he is 15 years old and remained in good health, free of infections or other complication to date. Conclusion: Genetic analysis is helpful for the diagnosis of WAS patients; our patient’s mutation was found to cause a mild phenotype of WAS. Statement of Novelty: We describe a patient with a mild phenotype of WAS with a novel mutation in the WASP gene, thus, expanding the spectrum of WASP gene mutations.

COVID-19 post-vaccination recommendations in primary immunodeficiency

The COVID-19 pandemic has proven a very difficult and challenging time for humanity to combat. Science stood up to the challenge in the most admirable manner by producing an unprecedented vaccine against SARS-COV-2. This highly effective vaccine was also recommended and administered to individuals with inborn errors of immunity that lead to primary immunodeficiency. While multiple studies have confirmed the efficacy of the vaccine in preventing significant disease in the general public, this protective effect has not been thoroughly evaluated in immune compromised hosts. Here, we provide post-vaccination recommendations for individuals with primary immunodeficiency, including the need for a third booster shot and considerations for antibody titre testing.

Diversity and Inclusion in Science

The complexity of most primary immunodeficiencies together with the increasingly complicated treatment regimens require a working partnership between the patient, their families, and the medical team. As a woman in medicine in general, and in clinical immunology and allergy in particular, I find it very important to work as a respected, valued, and equal part of a team, with a dedicated contribution to improve patient care and partake in research. Equally important is having the safety of a balanced family life and physical/mental health and wellness. I find myself very lucky at this point in my life, being part of a great physician team and having full support from my spouse

Chronic mucocutaneous Candidiasis caused by a novel STAT1 mutation: a report of 4 patients

Background: Chronic mucocutaneous Candidiasis (CMCC) is characterized by recurrent or persistent fungal infections of the skin, nails, and oral and genital mucosae. There are several underlying genetic causes for CMCC, with mutations in Signal Transducer and Activator of Transcription-1 (STAT1) accounting for the majority of cases. Aim: To broaden the genotypic spectrum of CMCC caused by STAT1 mutations. Methods: We evaluated a young patient and her family with CMCC. Immune workup and targeted gene sequencing were performed. Results: The proband presented at 7 years of age with persistent oral thrush. Immune evaluation revealed her cellular and humoral immunity to be within normal range. Given that her family history was significant for oral lesions in father, siblings, and paternal family members, STAT1 gene sequencing was performed. A novel heterozygous missense c.G799A, predicting a p.Ala267Thr amino acid change within the coiled-coil domain, was identified in our patient and 3 of her family members. Conclusion: Gain-of-function mutations in STAT1 have been associated with a variety of phenotypes, ranging from isolated CMCC to severe fatal combined immunodeficiency, mycobacterial infections, autoimmune disorders, as well as malignancy and aneurysms. Here, we describe a novel STAT1 mutation, c.G799A, resulting in a very mild phenotype of isolated CMCC in 4 members of one kindred. Statement of Novelty: We describe 4 patients with a mild phenotype of CMCC caused by a novel STAT1 heterozygous mutation.

COVID-19 vaccination for patients with primary immunodeficiency

The worldwide tally of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, causing novel coronavirus disease 2019 (COVID-19), currently approaches 149.7 million (as of April 30, 2021). Canada’s cases amount to 1,211,083 confirmed infections and 24,169 deaths. In the midst of the pandemic and a third wave of infections, programs aimed at widespread vaccination against COVID-19 remain an essential stop-gap to slow the spread of infection and help achieve protective herd immunity. Patients with primary immunodeficiency (PID) have impaired immune responses and may be at greater risk of severe illness due to COVID-19, thus, are strongly recommended to avoid interactions with those outside of their immediate household “bubble”, practice hand hygiene, and wear masks when spending time outside or in enclosed spaces where close contact with other people cannot be avoided. With the ongoing rollout of COVID-19 vaccinations, we provide here recommendations for patients with PID. It is important to note that individuals who are immunocompromised should always consult their immunologist for additional considerations/contraindications when reviewing their suitability for vaccination.