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

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.

Impaired humoral immune response in a COVID-19 patient with chronic lymphocytic leukemia complicated by spontaneous pneumomediastinum and hemophagocytic lymphohistiocytosis syndrome

“…An H-score calculated afterwards estimated a 95.5% probability of HLH [2]. In accordance with the available literature, B-cell depletion, dysregulated humoral immunity and a high H-score are independent predictors of mortality in COVID-19, which elucidate the unfavorable prognosis in our patient [3,4]. In contrast, the researchers have recently underlined that there is lack of association between level of SARS-CoV-2 neutralizing antibodies as a single parameter and severity of the disease [5].…”

COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry

“…[25][26][27][28][29] More recently studies have reported unfavorable prognosis particularly in those with shorter duration between last rituximab infusion and infection. [30][31][32][33] These conflicting results may reflect heterogeneity in the diseases treated with rituximab, intensity of B cell depletion and IgG levels at infection onset and number of previous treatments. Similarly, the data regarding calcineurin inhibitors has been mixed.…”

Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy

“…While patients with IMIDs on BCDTs have been recognized to be vulnerable to severe COVID-19 infections, 3,4,6,7 relatively scant data exist regarding their risks for and outcomes of breakthrough infections 2,18 . The current cohort of breakthrough patients consisted of nearly equal numbers of patients with rheumatic and neuro-inflammatory disease and most (91.9%) were either fully vaccinated or boosted, with only 6 (8.1%) with incomplete vaccination.…”

“…While there is great heterogeneity in the capacity of specific immunosuppressive agents to limit the integrated immune response to both natural infection as well as vaccines, of particular concern is the class of B cell depleting therapies (BCDTs) widely used to treat an array of IMIDs. Before the introduction of vaccines, treatment of both rheumatic and neurologic IMIDs with such BCDTs was associated with more severe COVID-19 [3][4][5][6][7][8][9] . Furthermore, numerous studies have documented the capacity for BCDTs such as rituximab and ocrelizumab to profoundly impair humoral response to numerous vaccines including SARS-CoV-2 [10][11][12][13] .…”