B Cells and COVID-19: Lessons From Patients With Agammaglobulinemia and the Study of Functional B-Cell Polymorphisms

Speletas, Matthaios; Raftopoulou, Sofia; Farmaki, Evangelia; Gatselis, Nikolaos; Mouchtouri, Varvara A.; Hatzianastasiou, Sophia; Georgiadou, Sarah P.; Tsinti, Gerasimina; Tsachouridou, Οlga; Tseroni, Maria; Metallidis, Symeon; Dalekos, George Ν.; Eibel, Hermann; Hadjichristodoulou, Christos

doi:10.18176/jiaci.0726

Cited by 4 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Predominantly antibody deficiencies were the first most-common IEIs in children who experienced COVID-19 (n = 197, 27.7%) [ 8 , 19 , 27 , 28 , 34 , 36 , 40 , 42 , 45 , 46 , 49 , 50 , 52 , 55 , 62 – 66 , 71 , 73 , 74 , 80 , 81 , 83 , 85 , 91 , 92 , 95 , 97 , 105 , 108 , 114 , 117 , 120 , 122 , 124 , 125 , 129 , 130 ] (see Additional file 2 : Table S3). Among them, 53 have common variable immunodeficiency (CVID, 26.9% of all predominantly antibody deficiencies) [ 19 , 27 , 28 , 34 , 36 , 40 , 46 , 50 , 62 – 66 , 73 , 74 , 80 , 95 , 97 , 114 , 122 , 124 , 125 ], 45 have X-linked agammaglobulinemia (XLA, 22.8%) [ 8 , 19 , 34 , 40 , 42 , 46 , 49 , 50 , ...…”

Section: Resultsmentioning

confidence: 99%

“…The remaining 18 patients have other isotype, light chain, or functional deficiencies with generally normal numbers of B cells [including IgG subclass deficiency with IgA and/or IgM deficiency (n = 2) [ 108 ], IgG, IgA and IgM deficiencies (n = 2) [ 108 ], partial IgA deficiency (n = 1) [ 124 ], and low IgM level (n = 1) [ 124 ]]; selective IgM deficiencies (n = 3) [ 81 , 108 ]; specific antibody deficiency with normal immunoglobulin and B cells levels (n = 4) [ 40 , 65 ], unspecified predominantly antibody deficiency (n = 3) [ 65 , 95 ]; UNG deficiency (n = 1) [ 19 ] and APRIL deficiency (n = 1) [ 40 ]. The most frequent main genetic causes of predominantly antibody deficiencies in children infected with SARS-CoV-2 were BTK (n = 41) [ 8 , 19 , 34 , 40 , 46 , 49 , 50 , 52 , 63 , 65 , 71 , 73 , 74 , 85 , 91 , 92 , 95 , 97 , 105 , 117 , 120 , 129 ], NFKB2 (n = 4) [ 27 , 36 , 95 , 122 ], TNFRSF13B (n = 3) [ 62 , 114 , 125 ], PIK3CD (n = 3) [ 19 , 65 , 97 ], and PIK3R1 (n = 2) [ 45 , 63 ]. For patients with predominately antibody deficiencies who acquired SARS-CoV-2, the median interquartile range (IQR) age was 120 months [83–175], with a male predominance [n = 94, 47.7%] [ 8 , 19 , 27 , 28 , 34 , 40 , 42 , 45 , 46 <...…”

Section: Resultsmentioning

confidence: 99%

“…The most frequent main genetic causes of predominantly antibody deficiencies in children infected with SARS-CoV-2 were BTK (n = 41) [ 8 , 19 , 34 , 40 , 46 , 49 , 50 , 52 , 63 , 65 , 71 , 73 , 74 , 85 , 91 , 92 , 95 , 97 , 105 , 117 , 120 , 129 ], NFKB2 (n = 4) [ 27 , 36 , 95 , 122 ], TNFRSF13B (n = 3) [ 62 , 114 , 125 ], PIK3CD (n = 3) [ 19 , 65 , 97 ], and PIK3R1 (n = 2) [ 45 , 63 ]. For patients with predominately antibody deficiencies who acquired SARS-CoV-2, the median interquartile range (IQR) age was 120 months [83–175], with a male predominance [n = 94, 47.7%] [ 8 , 19 , 27 , 28 , 34 , 40 , 42 , 45 , 46 , 49 , 50 , 52 , 55 , 62 , 63 , 65 , 66 , 71 , 73 , 74 , 80 , 85 , 91 , 92 , 95 , 105 , 108 , 117 , 120 , 125 ,…”

Section: Resultsmentioning

confidence: 99%

“…For patients with predominately antibody deficiencies who acquired SARS-CoV-2, the median interquartile range (IQR) age was 120 months [83–175], with a male predominance [n = 94, 47.7%] [ 8 , 19 , 27 , 28 , 34 , 40 , 42 , 45 , 46 , 49 , 50 , 52 , 55 , 62 , 63 , 65 , 66 , 71 , 73 , 74 , 80 , 85 , 91 , 92 , 95 , 105 , 108 , 117 , 120 , 125 , 129 , 130 ], and majority of the patients belonged to White (Caucasian) (n = 144, 73.1%) [ 8 , 27 , 36 , 42 , 46 , 50 , 52 , 55 , 62 – 64 , 66 , 71 , 73 , 80 , 81 , 83 , 85 , 95 , 97 , 105 , 108 , 114 , 120 , 122 , 124 , 129 ], Hispanic (n = 30, 15.2%) [ 40 , 65 , 95 , 125 ] and Persian (n = 15, 7.6%) [ 19 , 28 , 34 , ...…”

Section: Resultsmentioning

confidence: 99%

“…In those predominantly antibody deficiencies patients, few studies reported on specific allele changes (n = 9, 4.6%) [ 27 , 36 , 49 , 62 , 114 , 120 , 122 , 125 , 129 ]. Reported modes of inheritance for the predominantly antibody deficiencies in children were autosomal recessive (n = 62, 31.5%) [ 19 , 28 , 34 , 40 , 46 , 50 , 63 , 73 ], X-linked (n = 46, 23.3%) [ 8 , 19 , 34 , 40 , 42 , 46 , 49 , 50 , 52 , 63 , 65 , 71 , 73 , 74 , 85 , 91 , 92 , 95 , 97 , 105 , 117 , 120 , 129 , 130 ], or autosomal dominant (n = 15, 7.6%) [ 19 , 27 , 36 , 45 , 52 , 62 , 63 , 65 , 83 , 95 , 97 , 114 , 122 , 125 ], however, mode of inheritance in these predominantly antibody deficiencies cases was unknown in a high percentage of patients (n = 120, 60.9%) [ 40 , 46 , 48 , 52 , 55 , 63 – 66 , 74 ,…”

Section: Resultsmentioning

confidence: 99%

See 4 more Smart Citations

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Alhumaid,

Al Mutared,

Al Alawi

et al. 2023

Allergy Asthma Clin Immunol

View full text Add to dashboard Cite

Background Inborn 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. Objectives To 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. Methods For 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. Results Of 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. Conclusion Children 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).

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Alhumaid,

Al Mutared,

Al Alawi

et al. 2023

Allergy Asthma Clin Immunol

View full text Add to dashboard Cite

show abstract

Rapid and high throughput assessment of cellular immunity against SARS-CoV-2 based on the ex vivo activation of genes in leukocyte assay with whole blood

Saito,

Couzinet,

Murakami

et al. 2024

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation

Rodríguez-Ubreva,

Calafell-Segura,

Calvillo

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency, marked by hypogammaglobulinemia, poor antibody responses, and increased infection susceptibility. The COVID-19 pandemic provided a unique opportunity to study the effects of prolonged viral infections on the immune responses of CVID patients. Here we use single-cell RNAseq and spectral flow cytometry of peripheral blood samples before, during, and after SARS-CoV-2 infection showing that COVID-19 CVID patients display a persistent type I interferon signature at convalescence across immune compartments. Alterations in adaptive immunity include sustained activation of naïve B cells, increased CD21 low B cells, impaired Th1 polarization, CD4 + T central memory exhaustion, and increased CD8 + T cell cytotoxicity. NK cell differentiation is defective, although cytotoxicity remains intact. Monocytes show persistent activation of inflammasome-related genes. These findings suggest the involvement of intact humoral immunity in regulating these processes and might indicate the need for early intervention to manage viral infections in CVID patients.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), constituted a threat to public health worldwide (https://covid19. who.int/). Although many COVID-19 patients are asymptomatic or experience mild symptoms, some patients experience hyperinflammatory responses that lead to severe disease that can evolve to severe lung dysfunction, multiorgan system failure, and death 1 . In addition, persistent and often debilitating sequelae are increasingly recognized in convalescent individuals 2 .

show abstract

B Cells and COVID-19: Lessons From Patients With Agammaglobulinemia and the Study of Functional B-Cell Polymorphisms

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 4 publications

References 11 publications

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review

Rapid and high throughput assessment of cellular immunity against SARS-CoV-2 based on the ex vivo activation of genes in leukocyte assay with whole blood

COVID-19 progression and convalescence in common variable immunodeficiency patients show dysregulated adaptive immune responses and persistent type I interferon and inflammasome activation

Contact Info

Product

Resources

About