SARS-CoV-2 infection and treatment in a cohort of patients with inborn errors of immunity.
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ABSTRACT:
SUBMITTER: Conti F
PROVIDER: S-EPMC9538295 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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SARS-CoV-2 infection and treatment in a cohort of patients with inborn errors of immunity.
Conti Francesca F Pacillo Lucia L Amodio Donato D Rivalta Beatrice B Moratti Mattia M Campoli Caterina C Zama Daniele D Corsini Ilaria I Giancotta Carmela C Bernardi Stefania S Naviglio Samuele S Cicalese Maria Pia MP Rabusin Marco M Aiuti Alessandro A Cancrini Caterina C Lanari Marcello M Viale Pierluigi P Palma Paolo P Pession Andrea A Finocchi Andrea A
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20220801 8
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Project description:PurposeThere is still scarce data on SARS-CoV-2 infection in patients with Inborn Errors of Immunity (IEI) and many unresolved questions. We aimed to describe the clinical outcome of SARS-CoV-2 infection in Brazilian IEI patients and identify factors influencing the infection.MethodsWe did a cross-sectional, multicenter study that included patients of any age affected by IEI and SARS-CoV-2 infection. The variables studied were sex, age, type of IEI, comorbidities (number and type), treatment in use for IEI, clinical manifestations and severity of SARS-CoV-2 infection.Results121 patients were included: 55.4% female, ages from six months to 74 yo (median age = 25.1 yo). Most patients had predominantly antibody deficiency (n = 53). The infection was mostly asymptomatic (n = 21) and mild (n = 66), and one child had multisystem inflammatory syndrome (MIS-C). We could not observe sex-related susceptibility, and there was a weak correlation between age and severity of infection. The number of comorbidities was higher in severe cases, particularly bronchiectasis and cardiopathy. There were no severe cases in hereditary angioedema patients. Six patients aged 2 to 74 years died, three of them with antibody deficiency.ConclusionThe outcome was mild in most patients, but the Case Fatality Ratio was higher than in the general population. However, the type of IEI was not a determining factor for severity, except for complement deficiencies linked to milder COVID-19. The severity of SARS-CoV-2 infection seems to be more related to older age, a higher number of comorbidities and type of comorbidities (bronchiectasis and cardiopathy).
| S-EPMC8221557 | biostudies-literature
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: Not available
| S-EPMC9978277 | biostudies-literature
Project description:COVID-19 manifestations range from asymptomatic to life-threatening infections. The outcome in different inborn errors of immunity (IEI) is still a matter of debate. In this retrospective study, we describe the experience of the of the Italian Primary Immunodeficiencies Network (IPINet). Sixteen reference centers for adult or pediatric IEI were involved. One hundred fourteen patients were enrolled including 35 pediatric and 79 adult patients. Median age was 32 years, and male-to-female ratio was 1.5:1. The most common IEI were 22q11.2 deletion syndrome in children (26%) and common variable immunodeficiency (CVID) in adults (65%). Ninety-one patients did not require hospital admission, and among these, 33 were asymptomatic. Hospitalization rate was 20.17%. Older age (p 0.004) and chronic lung disease (p 0.0008) represented risk factors for hospitalization. Hospitalized patients mainly included adults suffering from humoral immunodeficiencies requiring immunoglobulin replacement therapy and as expected had lower B cell counts compared to non-hospitalized patients. Infection fatality rate in the whole cohort was 3.5%. Seroconversion was observed is 86.6% of the patients evaluated and in 83.3% of CVID patients. 16.85% of the patients reported long-lasting COVID symptoms. All but one patient with prolonged symptoms were under IgRT. The fatality rate observed in IEI was slightly similar to the general population. The age of the patients who did not survive was lower compared to the general population, and the age stratified mortality in the 50-60 age range considerable exceeded the mortality from 50 to 60 age group of the Italian population (14.3 vs 0.6%; p < 0.0001). We hypothesize that this is due to the fact that comorbidities in IEI patients are very common and usually appear early in life.
| S-EPMC9020753 | biostudies-literature
Project description: Not available
| S-EPMC8443305 | 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:Clinical disease caused by the agent of tuberculosis, Mycobacterium tuberculosis, and by less virulent mycobacteria, such as bacillus Calmette-Guérin (BCG) vaccines and environmental mycobacteria, can result from inborn errors of immunity (IEIs). IEIs underlie more than 450 conditions, each associated with an impairment of the development and/or function of hematopoietic and/or non-hematopoietic cells involved in host defense. Only a minority of IEIs confer predisposition to mycobacterial disease. The IEIs underlying susceptibility to bona fide tuberculosis are less well delineated than those responsible for susceptibility to less virulent mycobacteria. However, all these IEIs share a defining feature: the impairment of immunity mediated by interferon gamma (IFN-γ). More profound IFN-γ deficiency is associated with a greater vulnerability to weakly virulent mycobacteria, whereas more selective IFN-γ deficiency is associated with a more selective predisposition to mycobacterial disease. We review here recent progress in the study of IEIs underlying mycobacterial diseases.
| S-EPMC9172628 | biostudies-literature
Project description:BackgroundInherited genetic defects in immune system-related genes can result in Inborn Errors of Immunity (IEI), also known as Primary Immunodeficiencies (PID). Diagnosis of IEI disorders is challenging due to overlapping clinical manifestations. Accurate identification of disease-causing germline variants is crucial for appropriate treatment, prognosis, and genetic counseling. However, genetic sequencing is challenging in low-income countries like Brazil. This study aimed to perform genetic screening on patients treated within Brazil's public Unified Health System to identify candidate genetic variants associated with the patient's phenotype.MethodsThirteen singleton unrelated patients from three hospitals in Rio de Janeiro were enrolled in this study. Genomic DNA was extracted from the peripheral blood lymphocytes of each patient, and whole exome sequencing (WES) analyses were conducted using Illumina NextSeq. Germline genetic variants in IEI-related genes were prioritized using a computational framework considering their molecular consequence in coding regions; minor allele frequency ≤ 0.01; pathogenicity classification based on American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines gathered from the VarSome clinical database; and IEI-related phenotype using the Franklin tool. The genes classification into IEI categories follows internationally recognized guidelines informed by the International Union of Immunological Societies Expert Committee. Additional methods for confirmation of the variant included Sanger sequencing, phasing analysis, and splice site prediction.ResultsA total of 16 disease-causing variants in nine genes, encompassing six different IEI categories, were identified. X-Linked Agammaglobulinemia, caused by BTK variations, emerged as the most prevalent IEI disorder in the cohort. However, pathogenic and likely pathogenic variants were also reported in other known IEI-related genes, namely CD40LG, CARD11, WAS, CYBB, C6, and LRBA. Interestingly, two patients with suspected IEI exhibited pathogenic variants in non-IEI-related genes, ABCA12 and SLC25A13, potentially explaining their phenotypes.ConclusionsGenetic screening through WES enabled the detection of potentially harmful variants associated with IEI disorders. These findings contribute to a better understanding of patients' clinical manifestations by elucidating the genetic basis underlying their phenotypes.
| S-EPMC10433585 | biostudies-literature