Immune Response to SARS-CoV-2 Infections in Children with Secondary Immunodeficiencies.

BACKGROUND AND PURPOSE: It is a matter of research, whether children with immunodeficiencies are able to generate an effective immune response to prevent SARS-CoV-2 reinfection. This study aimed to evaluate and compare the seroconversion rates and changes of lymphocyte subsets during COVID-19 in immunocompetent children and those with secondary immunodeficiencies. METHODS: In 55 children - 28 immunocompromised and 27 immunocompetent - hospitalized with confirmed SARS-CoV-2 infection, the level of IgG antibodies against the Spike protein was determined on two to three occasions. In those children from the study group whose immunosuppressive treatment did not alter during the study (n = 13) and in selected children from the control group (n = 11), flow cytometric evaluation of lymphocyte subsets was performed twice - 2 weeks and 3 months post-infection. RESULTS: Seroconversion reached 96.3% in both studied groups; however, the immunocompromised cohort achieved lower titers of detectable anti-S antibodies. There was no correlation between seroconversion or titers of antibodies and the total number of lymphocytes or their subsets. In the immunocompetent cohort, we reported a significant decrease in NK cells during the infection. In this group and the entire study population, a positive correlation was noticed between the CD4 + /CD8 + T cell ratio and the severity of COVID-19 pneumonia. CONCLUSIONS: Children with secondary immunodeficiencies seroconvert in equal percentages but with a significantly lower titer of anti-S antibodies compared to their immunocompetent peers. The lower number of NK cells in the immunocompetent cohort may result from their participation in antiviral immunity, whereas reduced CD4 + /CD8 + T cell ratios among immunocompromised children may be a protective factor against a severe COVID-19.

Case report: Successful allogeneic stem cell transplantation in a child with novel GATA2 defect associated B-cell acute lymphoblastic leukemia.

GATA-binding protein 2 (GATA2) is a transcription factor responsible for the regulation of blood cell proliferation, differentiation, and maintenance in hematopoietic stem cells. Here, we describe successful bone marrow transplantation in a carrier of a novel GATA2 pathogenic variant who was diagnosed with immunodeficiency a few years after completion of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) treatment. At the age of 4 years, the patient was diagnosed with and treated for BCP-ALL. Antileukemic therapy was complicated by pulmonary cryptococcosis. Two years after completion of the maintenance therapy, the child was consulted by an immunologist because of recurrent respiratory tract infections and an episode of sepsis. Flow cytometry revealed deep monocytopenia, lymphopenia, absence of B lymphocytes, considerably reduced NK cells, poor thymic T lymphocyte production, minor defects in T cell maturation, and absence of TCRγδ+ T cells. The presence of the likely pathogenic, heterozygous missense variant within exon 5 of GATA2 (NM_032638.5: c.1047T>G, Cys349Trp) was identified in the proband and confirmed in the father of the patient, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor due to myelodysplastic syndrome with excess blasts at the age of 22 years. An allogeneic hematopoietic stem cell transplantation with a reduced toxicity conditioning protocol was performed using a matched sibling donor. Pre-transplant conditioning included fludarabine (5 × 30 mg/m2), treosulfan (3 × 14 g/m2), and thiotepa (10 mg/kg). Complete donor chimerism was achieved on post-transplant day 17. During the 12 months of the posttransplant observation period, she remained free from symptoms of acute or chronic graft-versus-host disease, and immunosuppressive treatment was therefore stopped. This is the second reported case of BCP-ALL in a patient with GATA2 deficiency, and the first successfully treated with a reduced-toxicity conditioning HSCT protocol. The co-occurrence of lymphoid malignancies and primary immunodeficiencies points to the role of genetic counseling and family screening for possible cancer predisposition syndromes prior to the selection of related HSCT donors.

Long-COVID in immunocompromised children.

Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child's general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children - 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%). Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%). CONCLUSIONS: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings. WHAT IS KNOWN: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 - mainly mild or asymptomatic - among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups. WHAT IS NEW: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.

Different Course of SARS-CoV-2 Infection in Two Adolescents With Other Immunosuppressive Factors.

Even after two years of the Coronavirus Disease 2019 (COVID-19) pandemic, despite known risk factors, we are still unable to predict the severity of the infection in specific patients. Due to the contradictory data, the protective role of immunosuppression in preventing the severe course of the infection remains uncertain. Therefore, we want to discuss the influence of several immunosuppressive factors on the COVID-19 pattern in children, based on two case reports regarding 17-year-old boys with other immunosuppressive factors and a completely different course of the disease. The first patient suffered from AIDS, syphilis and primary central nervous system B-cell lymphoma, treated with radiotherapy. He experienced a light path of the infection, presenting only periodically appearing cough with no X-ray inflammatory changes. Nevertheless, due to the risk of severe COVID-19 and transient hypoxia, remdesivir was administered. He remained in a generally good condition and his follow-up did not reveal any noticeable complications. The second patient was characterised by Down syndrome, obesity, polyarteritis nodosa and chronic immunosuppressive therapy. He developed massive pneumonia, required treatment in the intensive care unit with the use of mechanical ventilation, remdesivir and anakinra. Despite the initial improvement of his general condition, including the degree of lung involvement and respiratory function, he developed an intracerebral haemorrhage, leading to brain herniation and ultimately death. In conclusion, HIV infection, oncological and immunosuppressive treatment do not seem to predispose to the severe course of COVID-19, whereas Down syndrome and obesity do.

Prevalence and Course of SARS-CoV-2 Infection among Immunocompromised Children Hospitalised in the Tertiary Referral Hospital in Poland.

The aim of this retrospective study was the assessment of the prevalence, clinical characteristics, and the comparison of the course of SARS-CoV-2 infection in children with and without immunodeficiency that were admitted to the COVID-19 Subunit of the tertiary referral hospital in Warsaw, Poland. We analysed 313 children hospitalised in the COVID-19 Subunit. The analysis was performed on the total study group and subgroups of children with and without immunodeficiency. In each group, clinical data and laboratory test results were analysed. Of the 68 children with isolated fevers, only seven (11.76%) were diagnosed with COVID-19, whereas among those with the accompanying features of respiratory or gastrointestinal infection, only one (3.23%) and ten (16.95%) patients tested positive, respectively. In both groups, the course of the infection was mainly asymptomatic or mild. The children with immunodeficiencies had lower white blood cell and lymphocyte counts, lower haemoglobin levels, and higher urea levels but did not differ in other biochemical variables. To conclude, the most frequently reported symptoms of COVID-19 indicate that this disease among children is only a small percentage. In both groups, the responses to the infection were comparable in terms of the mild clinical symptoms and the laboratory test results. Therefore, SARS-CoV-2 infection should not alter the chronic treatment of underlying diseases.

Effects of Hyperbaric Oxygen Therapy in Children with Severe Atopic Dermatitis.

In the course of atopic dermatitis (AD), the overactivity of the immune system, associated with predominant Th2 lymphocyte responses, is observed, which leads to an increased inflammatory reaction. Cases of a severe course of atopic dermatitis lead to the search for new therapeutic options. The aim of this study was to assess the effects of hyperbaric oxygen therapy (HBOT) treatment for severe cases of AD in children. A total of 15 children with severe AD underwent therapy. The influence of HBOT on the clinical course of AD and immunomodulatory effect of the therapy was analyzed by the SCORAD and objective SCORAD (oSCORAD) scales and by determining the serum concentration of immunological parameters (blood: nTreg lymphocytes, CD4+CD25highCD127-FOXP3+, NKT lymphocytes CD3+, CD16/56+, and serum: total IgE, cytokines IL-4, IL-6, and IL-10, before and after the 30-day treatment cycle). The study showed a significant effect of the therapy on the improvement of the skin condition. In all children, a reduction in the extent and intensity of skin lesions, reduction of redness, swelling, oozing/crusting, scratch marks and skin lichenification after HBOT was observed. Patients also reported a reduction in the intensity of pruritus and an improvement in sleep quality after therapy. In all children, a statistically significant decrease in the serum level of IgE was observed. However, no statistically significant changes in the blood levels of IL-4, IL-6 and IL-10, as well as the percentage of CD4+CD25highCD127-FOXP3+ Treg and NKT lymphocytes, were found. In conclusion, the use of hyperbaric therapy has a positive impact on treatment results in children with a severe course of atopic dermatitis.

Secondary cervical cancer prevention in routine prenatal care - coverage, results and lessons for the future.

OBJECTIVES: Cervical cancer is the fourth most common type of cancer among women worldwide and one of the most common malignancies diagnosed in gravidas. Therefore, routine antenatal Pap smear is such an important examination. The aim of the study was to assess the prevalence of Pap smear performance during prenatal care and to determine possible factors affecting it. MATERIAL AND METHODS: A self-composed questionnaire was distributed among 638 women managed in a tertiary obstetric referral center. 33 questions regarded cervical cancer prevention and risk factors. RESULTS: 96.9% of respondents had undergone Pap smear and 80.6% had it performed during pregnancy. For 11.5% women Pap smear in pregnancy was the first one in their life. The most common reasons for lack of Pap smear performance were: no subjective need to perform it (40.9%), no doctor's recommendation (28.6%) and lack of gynecological care (16.3%). Among professionally active women the percentage of those who had not undergone Pap smear during pregnancy was statistically higher (28.5%) than among those who were on sick leave (13.5%) (p = 0.0003). Also, younger women were at risk of less frequent participation in cervical cancer screening CONCLUSIONS: Although performance of Pap smear among surveyed patients was relatively high, there was a significant group of women who had undergone their first test during pregnancy, which makes secondary cervical cancer prevention in prenatal care a useful prophylactic strategy. Special attention should be given to younger and professionally active women.