COVID-19-Related Encephalitis in a Child with PIK3CD Defect

Introduction: COVID-19 related encephalitis has been reported in pediatric patients;however, there are no reports in patients with inborn errors of immunity (IEI). Activated PI3K Delta Syndrome (APDS) is a disease of immune dysregulation with immunodeficiency, autoimmunity, and abnormal lymphoproliferation resulting from autosomal dominant gain-offunction variants in PIK3CD or PIK3R1 genes. We investigate a family with APDS, one mother and three children, one of whom developed COVID-19 related encephalitis. Method(s): Patients were consented to an IRB-approved protocol at our institution. Medical records and detailed immunophenotyping were reviewed. Family members were sequenced for IEI with a targeted gene panel. Result(s): The index case is a 10-year-old female with a known pathogenic variant in PIK3CD (c.3061 G > A, p.Glu1021Lys), who contracted SARS-COV-2 despite one COVID-19 vaccination in the series. Her disease course included COVID-related encephalitis with cerebellitis and compression of the pons, resulting in lasting truncal ataxia and cerebellar mutism. At that time, the patient was not on immunoglobulin replacement therapy (IgRT), but was receiving Sirolimus. Besides the index case, 3 family members (2 brothers, 1 mother) also share the same PIK3CD variant with variable clinical and immunological phenotypes. All children exhibited high transitional B-cells, consistent with developmental block to follicular B cell stage. Increased non-class switched IgM+ memory B cells and skewing towards CD21lo B cell subset, which is considered autoreactive-like, was observed in all patients. Of note, the patient had low plasmablasts, but normal immunoglobulins. Of her family members, only one was receiving both sirolimus and IgRT. Conclusion(s): We describe a rare case of COVID-19-related encephalitis in a patient with inborn error of immunity while not on IgRT. This may indicate infection susceptibility because of a lack of sufficient immunity to SARS-CoV-2, unlike the rest of her family with the same PIK3CD variant.Copyright © 2023 Elsevier Inc.

An unexpected diagnosis: Good's syndrome

Case report Introduction: Good's syndrome (GS) represents an acquired adult-onset immunodeficiency associated with thymoma. GS affects patients over 40 yrs in form of recurrent infections especially with encapsulated bacteria, opportunistic viral and fungal invasions as a result of combined T/B cell deficiency. The imbalanced immunity may also provoke autoimmune phenomena and tumorigenesis. Case report: We present a 40-year- old male with a newly onset of dull thoracic pain and with no history of previous diseases. Chest CT revealed an anterior mediastinal mass in 2021, without lympadenopathy. A CT-guided core biopsy was suggestive for malignant thymoma, so the patient underwent total thymectomy. Histology indicated a thymoma of the AB type (WHO), and stage I. (Masaoka-Koga);(pT1a pNo). After surgery he was readmitted due to recurrent febrile respiratory tract infections, caused by Gram (-) bacteria or fungi;combination therapy of antibiotics and antifungal drugs was used. With suspicion of GS we determined immunoglobulin levels and the distribution of peripheral lymphocyte subsets. Hypogammaglobulinemia (IgG/A/M), and by flow cytometry markedly reduced peripheral B cells, and an inverse ratio of CD4+/CD8+ T cells were detected, confirming the diagnosis. Blast transformation assay indicated decreased T cell proliferation. Thus, following thymectomy, the patient exhibited severe T/B cell alterations with subsequent recurrent infections. Detailed autoantibody and complement analyses indicated no autoimmune laboratory abnormalities so far. There are still no effective protocols for GS therapy, except of antibiotic prophylaxis, preventive vaccination, and regular immunoglobulin replacement, so IVIG was introduced. As part of the follow-up repeated CT indicated no thymoma recurrence or metastasis. In December 2021 the vaccination refusing patient survived a severe bilateral organizing pneumonia secondary to SARS-CoV2. Conclusion(s): Incidence of the thymic epithelial tumor, thymoma is 0.15-0.33 cases/100.000/year. Depending on histology it could be linked to various immunological abnormalities. Appr. 0.2%-6% of thymomas corresponds to GS. GS, with a still elusive pathogenesis is considered as an uncommon combined immunodeficiency of adults with a variable phenotype and certain similarities to CVID. The prevalence is estimated appr. as 1/500.000. Combination of the high infection susceptibility and concomitant autoimmune diseases could make the diagnosis a challenging task.

Non - pharmaceutical interventions for respiratory virus infection in children and its effect.

With the emergence of new respiratory virus,it is more apparent for the vulnerability of population to respiratory viral infection. Non -pharmaceutical interventions (NPIs) for respiratory virus infection have become the main way to prevent corona virus disease 2019. Some studies had proven its effectiveness. In addition,the NPIs also significantly reduced the incidence and hospitalization rate of other respiratory disease in children. NPIs for respiratory virus infection in children have its particularity and challenge. In daily life,it is important to guide children how to do the NPIs, so as to protect susceptible children and reduce the disease burden in children's health system. Therefore, the aerosol transmission, the specificity of the NPIs in children, and the impact on childhood respiratory diseases are described in this article, to improve the prevention of common respiratory diseases in children.Copyright © 2022 Chinese Medical Journals Publishing House Co.Ltd. All Rights Reserved.

On race, human variation, and who gets and dies of sepsis

COVID-19 has highlighted a brutal reality known for decades, that Black, Indigenous, and People of Color bear a disproportionate burden of US annual sepsis cases. While plentiful research funds have been spent investigating genetic reasons for racial disparities in sepsis, an abundance of research shows that sepsis incidence and mortality maps to indicators of colonial practices including residential segregation, economic and marginalization sepsis, and denial of care. Here we argue that sepsis risk is an immunological embodiment of racism in colonial states, that the factors contributing to sepsis disparities are insidious and systemic. We show that regardless of causative pathogen, or host ancestry, racialized people get and die of sepsis most frequently in a pattern repeatedly reiterated worldwide. Lastly, we argue that while alleviation of sepsis disparities requires radical, multiscale intervention, biological anthropologists have a responsibility in this crisis. While some of us can harness our expertise to take on the ground action in sepsis prevention, all of us can leverage our positions as the first point of contact for in depth human biology instruction on most college campuses. As a leading cause of death worldwide, and a syndrome that exhibits the interplay between human physiology, race and environment, sepsis is at the nexus of major themes in biological anthropology and is a natural fit for the field's curriculum. In adopting a discussion of race and sepsis in our courses, we not only develop new research areas but increase public awareness of both sepsis and the factors contributing to uneven sepsis burden.Copyright © 2022 The Authors. American Journal of Biological Anthropology published by Wiley Periodicals LLC.

An Overview About Pediatric Type 1 Diabetes Mellitus

Background: Diabetes mellitus (DM) represents one of the most common metabolic diseases in the world, with rising prevalence in recent decades. Most cases are generally classified into two major pathophysiological categories: type 1 diabetes mellitus (DM1), which progresses with absolute insulin deficiency and can be identified by genetic and pancreatic islet autoimmunity markers, and type 2 diabetes mellitus (DM2), which is the most prevalent form and involves a combination of resistance to the action of insulin with an insufficient compensatory response of insulin secretion. In the last two decades, in parallel with the increase in childhood obesity, there has also been an increase in the incidence of DM2 in young people in some populations. Other forms of diabetes may affect children and adolescents, such as monogenic diabetes (neonatal diabetes, MODY – maturity onset diabetes of the young, mitochondrial diabetes, and lipoatrophic diabetes), diabetes secondary to other pancreatic diseases, endocrinopathies, infections and cytotoxic drugs, and diabetes related to certain genetic syndromes, which may involve different treatments and prognoses. DM1 is considered an immuno-mediated disease that develops as a result of gradual destruction of insulin-producing pancreatic beta cells that eventually results in their total loss and complete dependence on exogenous insulin. Clinical presentation can occur at any age, but most patients will be diagnosed before the age of 30 years

Age and gender differences in COVID 19 morbidity and mortality in Nepal

Background The global health community has emphasized the importance of reporting epidemiological data by age and sex groups in the COVID-19 pandemic. However, age and sex disaggregated data of COVID-19 cases and deaths are rarely reported. Such data are very crucial for public to make truly informed choices about their own diseases risk and also for governments for public policy response. Objective To assess age and gender difference among COVID-19 cases and deaths in Nepal. Method This is a retrospective study which uses public data on COVID-19 cases and deaths released by Ministry of Health and Population, Government of Nepal from January to November, 2020. The data analysis was carried out using SPPS software version 26. Result Nepal reported 233,452 confirmed cases and 1,566 deaths of COVID-19 from 23 January 2020 to 30 November 2020. We found statistically significant differences on COVID-19 cases by age and gender in Nepal with higher number of cases among males of economically active age groups (20-60 years). Similarly, we found significant difference in COVID-19 mortality with more death occurred among male group compared to female group and with highest number of deaths among the people of above 60 years. Furthermore, we found differences in cases and deaths among provinces. Conclusion The age and gender differences in COVID cases and deaths in Nepal indicates needs of considering age and sex groups seriously while planning for testing, case management and vaccination against COVID-19 infections in Nepal. Copyright © 2020, Kathmandu University. All rights reserved.

Modeling Diagnostic Testing Strategies for SARS-CoV-2 to Minimize Societal Costs and Return People to Work

Background. The shift to more transmissible but less virulent strains of SARS-CoV-2 has altered the risk calculation for infection. Particularly among young adults, the economic burden of lost work due to isolation exceeds the economic burden of morbidity due to infection. Testing strategies must adapt to these changing circumstances. Methods. We modeled six testing strategies to estimate total societal costs for symptomatic people 18-49 years old: isolation of all individuals with no testing, rapid antigen test (RAg), RAg followed by a second RAg 48h later if first negative, RAg followed by a polymerase chain reaction (PCR) if negative, RAg followed by a PCR if positive, and PCR alone. We calculated costs for hypothetical cohorts of 100 symptomatic healthcare workers tested with each strategy;we included testing costs, lost wages, and hospitalization costs for the index, secondary, and tertiary cases. Key assumptions were 5% prevalence of infection, sensitivity of first/second RAg 40/80% with 97% specificity, PCR sensitivity/specificity 95/99%, all individuals isolate at symptom onset, are tested the same day, and isolate for 5 days if positive. RAg results were available the same day, PCR results were available the next day (Figure 1). One-way sensitivity analyses were performed for RAg sensitivity (20-80%) and positivity rate (1-80%). Results. The least expensive strategy was RAg alone (Figure 2). This was primarily driven by its low sensitivity, which reduced lost wages at the expense of missing cases. At a threshold for RAg sensitivity lower than 29%, PCR testing alone became the cheapest strategy. When the positivity rate was > 6% confirming a negative RAg with a PCR became the cheapest strategy, closely followed by PCR alone. At a positivity rate of > 29%, isolation without testing was cheapest followed by confirming a negative RAg with a PCR and by the serial RAg test strategies (Figure 3). Conclusion. In relatively young, healthy populations, a single rapid test was the least expensive strategy when the positivity rate was < 6%, testing that included PCR became cheapest at intermediate positivity, and empiric isolation was cheapest at positivity > 29%. Calibrating SARS-CoV-2 test strategies based on epidemiology may save societal costs.

Incidence, Resistance Patterns, and Outcomes of Secondary Bacterial and Fungal Infections in Critically Ill ICU Patients in the 2nd Wave of the COVID-19 Pandemic

Aim and background: The COVID-19 pandemic has raised significant concerns over secondary infections because of the widespread use of steroids, immunomodulators, and empiric antimicrobials as part of the recommended treatment protocol. Various studies have shown that COVID-19 infection by itself predisposes to secondary infections. During the 2nd wave of the COVID-19 pandemic, there has been an unprecedented epidemic of secondary invasive fungal infections. This study analyses the prevalence, details, and outcomes of secondary infections in critical COVID-19 patients admitted to a tertiary intensive care unit (ICU) in India. Materials and methods: Retrospective study of secondary infections in ICU patients between April and June 2021. Demographic data, details of immunomodulator therapy, secondary bacterial and fungal infections, antimicrobial susceptibility data, and clinical outcomes of these patients were analyzed. Results: 71/238 (29.83%) ICU patients developed secondary bacterial and fungal infections. The mortality in patients with secondary infections was significantly higher [80.28% (p < 0.05)], compared to overall ICU mortality of 51.68%. In patients with secondary infections, 67.6% were referred from other hospitals after receiving initial treatment and 64.79% had received various immunomodulator therapies. Patients on prolonged mechanical ventilation (>7 days) and indwelling central venous (>7 days) and urinary catheters (>7.5 days) had higher secondary infection rates and higher mortality. There was positive significant growth in 80 respiratory samples, 34 blood samples, and 17 urine samples. Gram-negative bacteria were isolated in 85.91% and 32.39% had fungal isolates. Klebsiella pneumoniae followed by Acinetobacter baumannii were the predominant bacteria and Candida spp followed by Mucormycosis were the predominant fungal pathogens. Multi-drug resistant (MDR) infections were common among the isolates (70.59%). 49.3% of secondary infection patients had polymicrobial infections including fungal infections with higher mortality of 83%. Conclusion: There is a significantly high incidence of secondary MDR bacterial and fungal infection including Mucormycosis in critically ill COVID-19 patients, with an adverse impact on mortality. Risk factors included the use of steroids, immunomodulators, severe COVID-19 infection, empiric broad-spectrum antibiotics, invasive ventilation, and central venous and urinary catheterization, and prolonged ICU stay.

Human leukocyte antigen in COVID-19, a forgott en immune recognition mechanism: a scoping review

introduction. hla alleles play a fundamental role in the development of the immune response against viral infections. objective. Gather the information available on the association of different hla alleles with increased protection or susceptibility;furthermore, the impact on complications associated with sars-cov-2 infection. methodology. An information search was carried out in the Scopus, PubMed/Medline, lilacs and Academic Google databases that answered the research question: What is the association between hla and sars-cov-2 infection and the severity of the illness? Records of clinical trials from the databases of the who International Clinical Trials Platform were included. results. It was found that the hla-a* 25: 01, hla-b* 46: 01 and hla-c* 01: 02 alleles were associated with greater susceptibility to infection, while the hla-a* 02: 01 alleles, hla-a* 24: 02 and hla-b*27: 07 were associated with greater severity of the disease and the alleles hla-a* 02: 02, hla-b* 15: 03 and hla-c* 12: 03 as protective factor in covid-19. conclusions. The association between susceptibility, protection and severity with the different types of hla are mainly reported in silico analysis, and its precision is limited, requiring support based on in vitro and in vivo experimental studies and clinical trials in different populations. A greater focus is needed on the affinity of the various hla alleles by the sars-cov-2 proteome to elucidate the immunopathogenesis of the disease.

ABO blood grouping and COVID-19: a hospital-based study in Eastern India

Background: Blood group has been stated to be one of the risk factors associated with viral diseases like dengue, hepatitis virus, Norwalk virus and even the coronavirus associated with 2003 severe acute respiratory syndrome (SARS) outbreak. In addition, anti-A antibodies in experimental models have been shown to inhibit the interaction between coronavirus and angiotensin converting enzyme (ACE) receptor of the host target cell, the major receptor involved in viral pathogenesis. Thus, several workers propose an association between ABO blood type and coronavirus disease- 2019 (COVID-19) disease in many previous studies. The present study was undertaken in the Eastern part of India in line with these authors to study the association of ABO blood group of patients with COVID susceptibility and severity. Methods: This is a retrospective study over a period of 6 months from June 2020 to November 2020 where patients who underwent quantitative real-time polymerase chain reaction (qRT-PCR) test for SARS-COV2 and having a recorded patient blood group type were considered. The qRT-PCR positive admitted cases were considered as cases, and qRT-PCR negative cases were considered as controls. Data were entered in Microsoft Excel format and analyzed by statistical method to obtain association. Results: Consecutively obtained 5000 qRT-PCR positive patients (cases) and 11,700 (controls) were included in the present study. The mean age of cases was higher (54.24 vs. 34. 67) than the controls. Among the cases, the highest number (2379;47.6%) of samples belonged to A blood group followed by B (1278;25.6%) while among the control group O blood group had the highest prevalence (4215;36%). Blood group A had a higher odd of testing positive (Odds ratio-2.552;CI 2.381–2.734;p < 0.0001) than all other blood groups. A blood group is also associated with higher risk of ICU admission (Odds ratio- 1.699;95% CI 1.515–1.905) and 65.3% of this group is also associated with high viral load which gives an indication of higher disease severity. Conclusion: Blood group A is associated with an increased susceptibility to COVID 19 infection than other blood groups. Cases of this blood group are also associated with more critical care needs and a higher viral load on testing.