Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies

Grammatikos, Alexandros P.; Donati, Matthew; Johnston, Sarah; Gompels, Mark

doi:10.3389/fimmu.2021.731643

Cited by 26 publications

(20 citation statements)

References 175 publications

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“…Within SARS-CoV-2 infected patients with inborn errors of immunity, CVID patients represent the largest proportion since CVID is the most commonly diagnosed/reported IEI ( 5 ), have more comorbidities and older age ( 5 ). Moreover, CVID patients have an increased risk for prolonged infections and a low probability to clear viruses as it has been demonstrated for SARS-CoV-2 ( 6 ) as well as for the poliovirus, in particular when the number of peripheral blood B lymphocytes is low ( 7 ). Genetic differences contribute to individual variations in the immune response to pathogens and in the response to immunization.…”

Section: Susceptibility To Vaccine-preventable Infectionsmentioning

confidence: 99%

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

2022

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CVID patients have an increased susceptibility to vaccine-preventable infections. The question on the potential benefits of immunization of CVID patients against SARS-CoV-2 offered the possibility to analyze the defective mechanisms of immune responses to a novel antigen. In CVID, as in immunocompetent subjects, the role of B and T cells is different between infected and vaccinated individuals. Upon vaccination, variable anti-Spike IgG responses have been found in different CVID cohorts. Immunization with two doses of mRNA vaccine did not generate Spike-specific classical memory B cells (MBCs) but atypical memory B cells (ATM) with low binding capacity to Spike protein. Spike-specific T-cells responses were also induced in CVID patients with a variable frequency, differently from specific T cells produced after multiple exposures to viral antigens following influenza virus immunization and infection. The immune response elicited by SARS-CoV-2 infection was enhanced by subsequent immunization underlying the need to immunize convalescent COVID-19 CVID patients after recovery. In particular, immunization after SARS-Cov-2 infection generated Spike-specific classical memory B cells (MBCs) with low binding capacity to Spike protein and Spike-specific antibodies in a high percentage of CVID patients. The search for a strategy to elicit an adequate immune response post-vaccination in CVID patients is necessary. Since reinfection with SARS-CoV-2 has been documented, at present SARS-CoV-2 positive CVID patients might benefit from new preventing strategy based on administration of anti-SARS-CoV-2 monoclonal antibodies.

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Section: Susceptibility To Vaccine-preventable Infectionsmentioning

confidence: 99%

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

2022

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“…In contrast, most studies indicate patients with X-linked agammaglobulinemia (XLA) without comorbidities appear to be at lower risk, inferring antibodies can in some circumstances be detrimental (17)(18)(19)(20). Some authors are however less certain about the protective effect of XLA in COVID-19 outcomes (21,22).…”

Section: Patients At Increased Riskmentioning

confidence: 99%

Common Variable Immunodeficiency Disorders as a Model for Assessing COVID-19 Vaccine Responses in Immunocompromised Patients

et al. 2022

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“…In one of the first published reports of 7 Italian cases of COVID-19 in patients affected by primary antibody deficiency (PAD) described a more severe clinical course of COVID-19 in common variable immunodeficiency than in X-linked agammaglobulinemia patients, suggesting that a B cell dysfunction may be more dangerous than the complete lack of antibody production ( 8 ). It is indeed broadly recognized that a profound interplay exists between the host immune response and the COVID-19 course both in terms of susceptibility and clinical outcome ( 9 ). As a result, different published cohorts of patients with inborn errors of immunity (IEIs) reported mixed results depending on the underlying immunological defect ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study

et al. 2022

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BackgroundSeverity and mortality of COVID-19 largely depends on the ability of the immune system to clear the virus. Among various comorbidities potentially impacting on this process, the weight and the consequences of an antibody deficiency have not yet been clarified.MethodsWe used serum protein electrophoresis to screen for hypogammaglobulinemia in a cohort of consecutive adult patients with COVID-19 pneumonia, hospitalized in non-intensive care setting between December 2020 and January 2021. The disease severity, measured by a validated score and by the need for semi intensive (sICU) or intensive care unit (ICU) admission, and the 30-day mortality was compared between patients presenting hypogammaglobulinemia (HYPO) and without hypogammaglobulinemia (no-HYPO). Demographics, comorbidities, COVID-19 specific treatment during the hospital stay, disease duration, complications and laboratory parameters were also evaluated in both groups.ResultsWe enrolled 374 patients, of which 39 represented the HYPO cohort (10.4%). In 10/39 the condition was previously neglected, while in the other 29/39 hematologic malignancies were common (61.5%); 2/39 were on regular immunoglobulin replacement therapy (IgRT). Patients belonging to the HYPO group more frequently developed a severe COVID-19 and more often required sICU/ICU admission than no-HYPO patients. IgRT were administered in 8/39 during hospitalization; none of them died or needed sICU/ICU. Among HYPO cohort, we observed a significantly higher prevalence of neoplastic affections, of active oncologic treatment and bronchiectasis, together with higher prevalence of viral and bacterial superinfections, mechanical ventilation, convalescent plasma and SARS-CoV-2 monoclonal antibodies administration during hospital stay, and longer disease duration. Multivariate logistic regression analysis and Cox proportional hazard regression confirmed the impact of hypogammaglobulinemia on the COVID-19 severity and the probability of sICU/ICU admission. The analysis of the mortality rate in the whole cohort showed no significant difference between HYPO and no-HYPO.ConclusionsHypogammaglobulinemia, regardless of its cause, in COVID-19 patients hospitalized in a non-intensive care setting was associated to a more severe disease course and more frequent admission to s-ICU/ICU, particularly in absence of IgRT. Our findings emphasize the add-value of routine serum protein electrophoresis evaluation in patients admitted with COVID-19 to support clinicians in patient care and to consider IgRT initiation during hospitalization.

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Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies

Cited by 26 publications

References 175 publications

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

Common Variable Immunodeficiency Disorders as a Model for Assessing COVID-19 Vaccine Responses in Immunocompromised Patients

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study

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