COVID-19 in unvaccinated patients with inborn errors of immunity-polish experience.

At the beginning of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, patients with inborn errors of immunity (IEI) appeared to be particularly vulnerable to a severe course of the disease. It quickly turned out that only some IEI groups are associated with a high risk of severe infection. However, data on the course of Coronavirus Disease 2019 (COVID-19) in patients with IEI are still insufficient, especially in children; hence, further analyses are required. The retrospective study included 155 unvaccinated people with IEI: 105 children and 50 adults (67.7% and 32.3%, respectively). Male patients dominated in the study group (94 people, 60.6%). At least two comorbidities were found in 50 patients (32.3%), significantly more often in adults (56% vs. 21%). Adult patients presented significantly more COVID-19 symptoms. Asymptomatic and mildly symptomatic course of COVID-19 was demonstrated in 74.8% of the entire group, significantly more often in children (88.6% vs. 46%). Moderate and severe courses dominated in adults (54% vs. 11.4%). Systemic antibiotic therapy was used the most frequently, especially in adults (60% vs. 14.3%). COVID-19-specific therapy was used almost exclusively in adults. In the whole group, complications occurred in 14.2% of patients, significantly more often in adults (30% vs. 6.7%). In the pediatric group, there were two cases (1.9%) of multisystem inflammatory syndrome in children. Deaths were reported only in the adult population and accounted for 3.9% of the entire study group. The death rate for all adults was 12%, 15.4% for adults diagnosed with common variable immunodeficiency, 12.5% for those with X-linked agammaglobulinemia, and 21.4% for patients with comorbidity. The results of our study imply that vaccinations against COVID-19 should be recommended both for children and adults with IEI. Postexposure prophylaxis and early antiviral and anti-SARS-CoV-2 antibody-based therapies should be considered in adults with IEI, especially in those with severe humoral immune deficiencies and comorbidity.

Common variable immunodeficiency: different faces of the same disease.

INTRODUCTION: Common variable immunodeficiency (CVID) is one of the primary humoral immunodeficiencies. Despite the inborn nature, the first symptoms may appear in both children and adults. It is characterized by hypogammaglobulinaemia, severe infections, autoimmunity, allergies, and a predisposition to cancer. A delay in diagnosis is a significant problem: the time from the first symptoms of the disease to diagnosis and the implementation of proper treatment is usually very long. The consequence can be irreversible complications, which is why it is so important to promote knowledge on this immunodeficiency. AIM: To present the clinical and laboratory manifestation of primary immunodeficiencies such as common variable immunodeficiency. MATERIAL AND METHODS: The study presents the clinical and laboratory phenotype of 14 patients diagnosed with CVID, aged 5 to 58 years. A detailed medical history was taken, and clinical symptoms, immunological test results and complications were analysed in each patient. According to the ESID guidelines, in the differential diagnosis process of CVID the secondary hypogammaglobulinaemia was excluded. RESULTS: The follow-up period ranged from 39 to 133 months (median: 79 months). The median delay for the entire group was 5 years, which was shorter in children than in adults. In the presented group, the infectious phenotype (pneumonia, sinusitis) was dominant. Autoimmune and allergic diseases, malignant tumours and enteropathies have also been observed. CONCLUSIONS: The diagnostic delay is still too long, especially in adults, which can lead to serious and irreversible complications. Early diagnosis and appropriate treatment with intravenous and subcutaneous immunoglobulins reduces the frequency of infections and their potential complications.

Activated phosphoinositide 3-kinase delta syndrome 1 and 2 (APDS 1 and APDS 2): similarities and differences based on clinical presentation in two boys.

BACKGROUND: Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-of-function mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. CASE PRESENTATIONS: The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. CONCLUSIONS: Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions.

Correlation between Body Mass Index and Waist Circumference in Patients with Metabolic Syndrome.

Metabolic syndrome is defined as a group of coexisting metabolic risk factors, such as central obesity, lipid disorders, carbohydrate disorders, and arterial hypertension. According to the 2005 IDF criteria, subsequently revised in 2009, abdominal obesity is identified as the waist circumference of ≥80 cm in women and ≥94 cm in men. It is responsible for the development of insulin resistance. The aim of our study was to demonstrate a correlation between waist circumference (WC) and body mass index (BMI) in patients with metabolic syndrome in relation with hypertension, lipid disorders, and carbohydrate disorders. A cross-sectional two-site study was conducted in the Kuyavian-Pomeranian Voivodeship for 24 months. The study group consisted of 839 patients with diagnosed metabolic syndrome: 345 men (41.1%) and 494 women (58.9%) aged 32-80. In the study group, WC was found to be significantly correlated with BMI (R = 0.78, P < 0.01). The presence of overweight in men (BMI 25, 84 kg/m(2)) and even normal body weight in women (BMI 21,62 kg/m(2)) corresponds to an increased volume of visceral tissue in the abdomen. Introduction of primary prophylaxis in those people to limit the development of diabetes mellitus type 2 and cardiovascular diseases should be considered.