Prolonged Fecal Shedding of SARS-CoV-2 in Asymptomatic Children with Inborn Errors of Immunity.
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SUBMITTER: Mohanty MC
PROVIDER: S-EPMC8443305 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInborn errors of immunity (IEIs) are considered significant challenges for children with IEIs, their families, and their medical providers. Infections are the most common complication of IEIs and children can acquire coronavirus disease 2019 (COVID-19) even when protective measures are taken.ObjectivesTo estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children with IEIs and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with IEIs with COVID-19 illness.MethodsFor this systematic review, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guideline for studies on the development of COVID-19 in children with IEIs, published from December 1, 2019 to February 28, 2023, with English language restriction.ResultsOf the 1095 papers that were identified, 116 articles were included in the systematic review (73 case report, 38 cohort 4 case-series and 1 case-control studies). Studies involving 710 children with IEIs with confirmed COVID-19 were analyzed. Among all 710 IEIs pediatric cases who acquired SARS-CoV-2, some children were documented to be admitted to the intensive care unit (ICU) (n = 119, 16.8%), intubated and placed on mechanical ventilation (n = 87, 12.2%), suffered acute respiratory distress syndrome (n = 98, 13.8%) or died (n = 60, 8.4%). Overall, COVID-19 in children with different IEIs patents resulted in no or low severity of disease in more than 76% of all included cases (COVID-19 severity: asymptomatic = 105, mild = 351, or moderate = 88). The majority of children with IEIs received treatment for COVID-19 (n = 579, 81.5%). Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19 in children with IEIs occurred in 103 (14.5%). Fatality in children with IEIs with COVID-19 was reported in any of the included IEIs categories for cellular and humoral immunodeficiencies (n = 19, 18.6%), immune dysregulatory diseases (n = 17, 17.9%), innate immunodeficiencies (n = 5, 10%), bone marrow failure (n = 1, 14.3%), complement deficiencies (n = 1, 9.1%), combined immunodeficiencies with associated or syndromic features (n = 7, 5.5%), phagocytic diseases (n = 3, 5.5%), autoinflammatory diseases (n = 2, 3%) and predominantly antibody deficiencies (n = 5, 2.5%). Mortality was COVID-19-related in a considerable number of children with IEIs (29/60, 48.3%). The highest ICU admission and fatality rates were observed in cases belonging to cellular and humoral immunodeficiencies (26.5% and 18.6%) and immune dysregulatory diseases (35.8% and 17.9%) groups, especially in children infected with SARS-CoV-2 who suffered severe combined immunodeficiency (28.6% and 23.8%), combined immunodeficiency (25% and 15%), familial hemophagocytic lymphohistiocytosis (40% and 20%), X-linked lymphoproliferative diseases-1 (75% and 75%) and X-linked lymphoproliferative diseases-2 (50% and 50%) compared to the other IEIs cases.ConclusionChildren with IEIs infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the immunocompetent pediatric populations. Underlying immune defects does seem to be independent risk factors for severe SARS-CoV-2 infection in children with IEIs, a number of children with SCID and CID were reported to have prolonged infections-though the number of patients is small-but especially immune dysregulation diseases (XLP1 and XLP2) and innate immunodeficiencies impairing type I interferon signalling (IFNAR1, IFNAR2 and TBK1).
| S-EPMC10413516 | biostudies-literature
Project description:Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding was observed from the upper respiratory tract of a female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days, and of genomic and subgenomic RNA up to 105 days, after initial diagnosis. The infection was not cleared after the first treatment with convalescent plasma, suggesting a limited effect on SARS-CoV-2 in the upper respiratory tract of this individual. Several weeks after a second convalescent plasma transfusion, SARS-CoV-2 RNA was no longer detected. We observed marked within-host genomic evolution of SARS-CoV-2 with continuous turnover of dominant viral variants. However, replication kinetics in Vero E6 cells and primary human alveolar epithelial tissues were not affected. Our data indicate that certain immunocompromised individuals may shed infectious virus longer than previously recognized. Detection of subgenomic RNA is recommended in persistently SARS-CoV-2-positive individuals as a proxy for shedding of infectious virus.
| S-EPMC7640888 | biostudies-literature
Project description:BackgroundSARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEIs); however, little is known about immunogenicity and safety in these patients.ObjectiveWe sought to evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse events in a cohort of patients with IEIs.MethodsPlasma was collected from 22 health care worker controls, 81 patients with IEIs, and 2 patients with thymoma; the plasma was collected before immunization, 1 to 6 days before the second dose of mRNA vaccine, and at a median of 30 days after completion of the immunization schedule with either mRNA vaccine or a single dose of Johnson & Johnson's Janssen vaccine. Anti-spike (anti-S) and anti-nucleocapsid antibody titers were measured by using a luciferase immunoprecipitation systems method. Information on T- and B-cell counts and use of immunosuppressive drugs was extracted from medical records, and information on vaccine-associated adverse events was collected after each dose.ResultsAnti-S antibodies were detected in 27 of 46 patients (58.7%) after 1 dose of mRNA vaccine and in 63 of 74 fully immunized patients (85.1%). A lower rate of seroconversion (7 of 11 [63.6%]) was observed in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Previous use of rituximab and baseline counts of less than 1000 CD3+ T cells/mL and less than 100 CD19+ B cells/mL were associated with lower anti-S IgG levels. No significant adverse events were reported.ConclusionVaccinating patients with IEIs is safe, but immunogenicity is affected by certain therapies and gene defects. These data may guide the counseling of patients with IEIs regarding prevention of SARS-CoV-2 infection and the need for subsequent boosts.
| S-EPMC8418380 | biostudies-literature
Project description:The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs.
| S-EPMC11209597 | biostudies-literature
Project description:PurposeTo describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).MethodsUnvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.ResultsTwenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG+ 58.8% (10/17) (p=0.009); IgM+ 41.2% (7/17)(p<0.001); IgA+ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM+ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 -respectively) but there were no differences at remaining time points.ConclusionsOur IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC.
| S-EPMC9896004 | biostudies-literature
Project description: Not available
| S-EPMC9978277 | biostudies-literature
Project description:Wastewater-based epidemiology (WBE) was utilized to monitor SARS-CoV-2 RNA in sewage collected from manholes specific to individual student dormitories (dorms) at the University of Arizona in the fall semester of 2020, which led to successful identification and reduction of SARS-CoV-2 transmission events. Positive wastewater samples triggered clinical testing of residents within that dorm; thus, SARS-CoV-2 infected individuals were identified regardless of symptom expression. This current study examined clinical testing data to determine the abundance of asymptomatic versus symptomatic cases in these defined communities. Nasal and nasopharyngeal swab samples processed via antigen and PCR tests indicated that 79.2% of SARS-CoV-2 infections were asymptomatic, and only 20.8% of positive cases reported COVID-19 symptoms at the time of testing. Clinical data was paired with corresponding wastewater virus concentrations, which enabled calculation of viral shedding rates in feces per infected person. Mean shedding rates averaged from positive wastewater samples across all dorms were 7.30 ± 0.67 log10 genome copies per gram of feces (gc/g-feces) based on the N1 gene. Quantification of SARS-CoV-2 fecal shedding rates from infected individuals has been the critical missing component necessary for WBE models to measure and predict SARS-CoV-2 infection prevalence in communities. The findings from this study can be utilized to create models that can be used to inform public health prevention and response actions.
| S-EPMC8378060 | biostudies-literature
Project description:Inborn errors of immunity (IEIs) are a group of conditions whereby parts of the immune system are missing or dysfunctional. Once thought to primarily be a pediatric disorder, it is now estimated that more than 50% of worldwide incident IEI cases are accounted for by adults. Delayed diagnosis, late symptom onset, and IEI phenocopies can all lead to adult-onset recognition of IEIs. Lack of awareness regarding the diversity of IEI manifestations in adults contributes to diagnostic and treatment delays. Prompt referral to immunology is critical so that patients can receive a precise molecular diagnosis and targeted therapy when available. This article serves as a primer on IEIs in adulthood, highlighting the pathophysiology, epidemiology and clinical features. We present clinical vignettes of three key IEIs to assist clinicians in building illness scripts on their presentations. We provide a framework for the laboratory evaluation of IEIs and their initial treatment, with the aim of improving recognition and management of these conditions.
| S-EPMC10792788 | biostudies-literature
Project description:Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI. In this review, we aimed to comprehensively summarize and discuss the current understanding on the clinical features and the pathophysiology of endocrine disorders in IEI. This review is composed with three parts. First, we discuss the two major pathophysiology of endocrinopathy in IEI, autoimmune response and direct effects of the responsible genes. Next, the details of each endocrinopathy, such as growth failure, hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus (DM) are specified. We also illustrated potential endocrinopathy due to hematopoietic stem cell transplantation, including hypogonadism and adrenal insufficiency due to glucocorticoid therapy.
| S-EPMC8650088 | biostudies-literature
Project description:Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterized by a defect in the function of at least one, and often more, components of the immune system. The aim of this narrative review is to discuss the epidemiology, the pathogenesis and the correct management of tumours in patients with IEI. PubMed was used to search for all of the studies published over the last 20 years using the keywords: "inborn errors of immunity" or "primary immunodeficiency" and "cancer" or "tumour" or "malignancy". Literature analysis showed that the overall risk for cancer in children with IEI ranges from 4 to 25%. Several factors, namely, age of the patient, viral infection status and IEI type can influence the development of different cancer types. The knowledge of a specific tumour risk in the presence of IEI highlights the importance of a synergistic effort by immunologists and oncologists in tracking down the potential development of cancer in known IEI patients, as well as an underlying IEI in patients with newly diagnosed cancers. In the current genomic era, the creation of an international registry of IEI cases integrated with malignancies occurrence information is fundamental to optimizing the diagnostic process and to evaluating the outcomes of new therapeutic options, with the hope to obtain a better prognosis for these patients.
| S-EPMC8069273 | biostudies-literature