COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those with Humoral Immunodeficiency States:  A Scoping Review

Background: The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. Methods: To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. Results: Among patients with iatrogenic B-cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous forms of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. Conclusions: Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to control for clinical and biologic confounders of disease severity.

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COVID-19 Outcomes in Patients Undergoing B Cell Depletion Therapy and Those With Humoral Immunodeficiency States: A Scoping Review

10.21203/rs.3.rs-224753/v1 ◽

2021 ◽

Author(s):

Jessica M Jones ◽

Aiman J Faruqi ◽

James K Sullivan ◽

Cassandra Calabrese ◽

Leonard H Calabrese

Keyword(s):

B Cell ◽

Humoral Immunity ◽

Scoping Review ◽

Underlying Disease ◽

Cell Depletion ◽

B Cell Depletion ◽

Inborn Errors ◽

Humoral Immunodeficiency ◽

Increased Risk ◽

Immunodeficiency States

Abstract The role of humoral immunity has been well established in reducing infection risk and facilitating viral clearance in patients with COVID-19. However, the relationship between specific antibody responses and severity of COVID-19 is less well understood. To address this question and identify gaps in knowledge, we utilized the methodology of a scoping review to interrogate risk of infection and clinical outcomes of COVID-19 in patients with iatrogenic and inborn humoral immunodeficiency states based on existing literature. Among patients with iatrogenic B cell depletion, particularly with agents targeting CD20, our analysis found increased risk of severe COVID-19 and death across a range of underlying disease states. Among patients with humoral inborn errors of immunity with COVID-19, our synthesis found that patients with dysregulated humoral immunity, predominantly common variable immunodeficiency (CVID), may be more susceptible to severe COVID-19 than patients with humoral immunodeficiency states due to X-linked agammaglobulinemia and other miscellaneous form of humoral immunodeficiency. There were insufficient data to appraise the risk of COVID-19 infection in both populations of patients. Our work identifies potentially significant predictors of COVID-19 severity in patients with humoral immunodeficiency states and highlights the need for larger studies to identify clinical and biologic confounders of disease severity.

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Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

Arthritis Research & Therapy ◽

10.1186/ar3770 ◽

2012 ◽

Vol 14 (2) ◽

pp. R57 ◽

Cited By ~ 34

Author(s):

YK Onno Teng ◽

Gillian Wheater ◽

Vanessa E Hogan ◽

Philip Stocks ◽

EW Nivine Levarht ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

B Cell ◽

Humoral Immunity ◽

Cell Depletion ◽

B Cell Depletion ◽

Refractory Rheumatoid Arthritis

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Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques

Infection and Immunity ◽

10.1128/iai.00083-16 ◽

2016 ◽

Vol 84 (5) ◽

pp. 1301-1311 ◽

Cited By ~ 47

Author(s):

Jiayao Phuah ◽

Eileen A. Wong ◽

Hannah P. Gideon ◽

Pauline Maiello ◽

M. Teresa Coleman ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

B Cells ◽

B Cell ◽

Humoral Immunity ◽

Nonhuman Primates ◽

Acute Infection ◽

Cell Depletion ◽

B Cell Depletion ◽

Content Type ◽

The Impact

Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses againstMycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model ofM. tuberculosisinfection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells inM. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response inM. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined.

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