COVID-19 in Patients Receiving CD20-depleting Immunochemotherapy for B-cell Lymphoma

Abstract

The clinical and immunological impact of B-cell depletion in the context of coronavirus disease 2019 (COVID-19) is unclear. We conducted a prospectively planned analysis of COVID-19 in patients who received B-cell depleting anti-CD20 antibodies and chemotherapy for B-cell lymphomas. The control cohort consisted of age- and sex-matched patients without lymphoma who were hospitalized because of COVID-19. We performed detailed clinical analyses, in-depth cellular and molecular immune profiling, and comprehensive virological studies in 12 patients with available biospecimens. B-cell depleted lymphoma patients had more severe and protracted clinical course (median hospitalization 88 versus 17 d). All patients actively receiving immunochemotherapy (n = 5) required ICU support including long-term mechanical ventilation. Neutrophil recovery following granulocyte colony stimulating factor stimulation coincided with hyperinflammation and clinical deterioration in 4 of the 5 patients. Immune cell profiling and gene expression analysis of peripheral blood mononuclear cells revealed early activation of monocytes/macrophages, neutrophils, and the complement system in B-cell depleted lymphoma patients, with subsequent exacerbation of the inflammatory response and dysfunctional interferon signaling at the time of clinical deterioration of COVID-19. Longitudinal immune cell profiling and functional in vitro assays showed SARS-CoV-2-specific CD8 + and CD4 + T-effector cell responses. Finally, we observed long-term detection of SARS-CoV-2 in respiratory specimens (median 84 versus 12 d) and an inability to mount lasting SARS-CoV-2 antibody responses in B-cell depleted lymphoma patients. In summary, we identified clinically relevant particularities of COVID-19 in lymphoma patients receiving B-cell depleting immunochemotherapies.

SARS-CoV-2 evolution and immune escape in immunocompromised patients treated with exogenous antibodies

“…Thus, our results raise interesting questions about the role of CD8 + T cells in immunocompromised patients. First, our results confirm that patients with B cell deficiencies can elicit effector T cells 32 . Other studies have observed functional SARS-CoV-2-specific CD4 + and CD8 + T cell responses in patients with B cell deficiencies, including higher magnitude CD8 + than CD4 + T cell responses 1,32,33 .…”

“…First, our results confirm that patients with B cell deficiencies can elicit effector T cells 32 . Other studies have observed functional SARS-CoV-2-specific CD4 + and CD8 + T cell responses in patients with B cell deficiencies, including higher magnitude CD8 + than CD4 + T cell responses 1,32,33 . However, those studies were smaller or did not also examine humoral responses.…”

Successful Treatment of Persistent SARS-CoV-2 Infection in a B-Cell Depleted Patient with Activated Cytotoxic T and NK Cells: A Case Report

“…In the same study healthy age-and gender-matched individuals who recovered from COVID-19 were also characterized by increased numbers of CD8+ TEMRA cells. Interestingly, severe course of SARS-CoV-2 infection in B-cell deficient patients was associated with significantly lower proportions of TEMRA cells within T CD8+ cell subset [19]. These results suggest that CD8+ TEMRA cells may be responsible for the control of SARS-CoV-2 and simultaneously can serve as a marker of positive clinical outcome.…”

Emergence of SARS-CoV-2 resistance mutations in a patient who received anti-SARS-COV2 spike protein monoclonal antibodies: a case report

“…Despite promptly receiving anti-S protein mAbs after the SARS-CoV-2 infection diagnosis, our patient developed severe COVID-19, highlighting the therapeutic difficulties associated with COVID-19 in immunocompromised hosts. The severity of the disease in lymphoma patients receiving chemotherapy combined with anti-CD20 monoclonal antibodies has been reported [ 13 , 14 ]. The delayed onset of symptomatic disease, compared to the general population, has also been reported in this specific population [ 15 ].…”