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1.
J Allergy Clin Immunol ; 149(6): 1949-1957, 2022 06.
Article in English | MEDLINE | ID: covidwho-1783444

ABSTRACT

BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. OBJECTIVES: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. METHODS: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. CONCLUSIONS: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , COVID-19 , Genetic Diseases, Inborn , Immunologic Deficiency Syndromes , 2019-nCoV Vaccine mRNA-1273/blood , 2019-nCoV Vaccine mRNA-1273/immunology , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Adult , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Common Variable Immunodeficiency/genetics , Common Variable Immunodeficiency/immunology , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/immunology , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immunologic Deficiency Syndromes/blood , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/immunology , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
Clin Immunol ; 234: 108897, 2022 01.
Article in English | MEDLINE | ID: covidwho-1606333

ABSTRACT

Rituximab (RTX), an important therapeutic option for patients with rheumatic diseases, has been shown to reduce immune responses to various vaccines. We asked whether following SARS-CoV-2 vaccination, response rates in RTX treated patients are reduced and whether specific patient characteristics influence the responses. We recruited patients on chronic RTX therapy undergoing anti-SARS-CoV2 vaccination and measured the post-vaccination anti-spike IgG antibody levels. The median time from pre-vaccination RTX infusion to vaccination and from vaccination to the post-vaccination RTX infusion was 20.5 weeks and 7.2 weeks respectively. Only 36.5% of patients developed measurable titers of IgG anti-SARS-CoV-2 spike antibody after vaccination. Hypogammaglobulinemia (IgG and/or IgM) but not timing of vaccination, B cell numbers, or concomitant immune suppressive medications, correlated with sero-negativity (p = 0.004). Our results underscore the fact that even after B cell reconstitution, RTX induced chronic hypogammaglobulinemia significantly impairs the ability of the immune system to respond to SARS-CoV-2 vaccination.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunogenicity, Vaccine/immunology , Rheumatic Diseases/drug therapy , Rituximab/therapeutic use , SARS-CoV-2/immunology , Agammaglobulinemia/immunology , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , B-Lymphocytes/immunology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Prospective Studies , Rheumatic Diseases/immunology , Vaccination/methods
3.
Curr Opin Allergy Clin Immunol ; 21(6): 525-534, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1447630

ABSTRACT

PURPOSE OF REVIEW: The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). RECENT FINDINGS: Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. SUMMARY: In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/genetics , Agammaglobulinemia/complications , COVID-19/immunology , Genetic Diseases, X-Linked/complications , SARS-CoV-2/immunology , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , COVID-19/diagnosis , COVID-19/virology , Evolution, Molecular , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Severity of Illness Index
4.
Front Immunol ; 12: 731643, 2021.
Article in English | MEDLINE | ID: covidwho-1412494

ABSTRACT

In the era of COVID-19, understanding how our immune system responds to viral infections is more pertinent than ever. Immunodeficiencies with very low or absent B cells offer a valuable model to study the role of humoral immunity against these types of infection. This review looks at the available evidence on viral infections in patients with B cell alymphocytosis, in particular those with X-linked agammaglobulinemia (XLA), Good's syndrome, post monoclonal-antibody therapy and certain patients with Common Variable Immune Deficiency (CVID). Viral infections are not as infrequent as previously thought in these conditions and individuals with very low circulating B cells seem to be predisposed to an adverse outcome. Particularly in the case of SARS-CoV2 infection, mounting evidence suggests that peripheral B cell alymphocytosis is linked to a poor prognosis.


Subject(s)
Agammaglobulinemia/immunology , B-Lymphocytes/immunology , COVID-19/pathology , Common Variable Immunodeficiency/immunology , Genetic Diseases, X-Linked/immunology , Severe Combined Immunodeficiency/immunology , Thymoma/immunology , B-Lymphocytes/cytology , COVID-19/immunology , Humans , Lymphocyte Count , SARS-CoV-2/immunology , Thymoma/therapy
6.
Front Immunol ; 12: 634181, 2021.
Article in English | MEDLINE | ID: covidwho-1177976

ABSTRACT

Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.


Subject(s)
Bacterial Infections/immunology , Immunocompromised Host , Immunoglobulins/deficiency , Primary Immunodeficiency Diseases/immunology , Respiratory Tract Infections/immunology , Agammaglobulinemia/blood , Agammaglobulinemia/immunology , Agammaglobulinemia/therapy , Animals , Bacterial Infections/blood , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Class I Phosphatidylinositol 3-Kinases/blood , Class I Phosphatidylinositol 3-Kinases/immunology , Common Variable Immunodeficiency/blood , Common Variable Immunodeficiency/immunology , Common Variable Immunodeficiency/therapy , Humans , Immunoglobulins/blood , Primary Immunodeficiency Diseases/blood , Primary Immunodeficiency Diseases/therapy , Prognosis , Respiratory Tract Infections/blood , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/prevention & control , Risk Assessment , Risk Factors
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