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.
【초록키워드】 COVID-19, coronavirus disease, Neutrophils, SARS-CoV-2, Hospitalized, mechanical ventilation, Hospitalization, complement, CD4, CD8, ICU, Peripheral blood, Chemotherapy, In vitro assay, Cohort, Clinical course, lymphoma, immune profiling, hyperinflammation, Gene expression analysis, Patient, interferon signaling, age, longitudinal, patients, B-cell, Anti-CD20 antibody, SARS-CoV-2 antibody response, Inflammatory response, Analysis, Immune cell, Clinical deterioration, monocytes/macrophages, granulocyte, mononuclear cell, Support, Activation, colony stimulating factor, biospecimens, responses, immunological, Cell, lymphomas, respiratory specimen, performed, subsequent, clinically, required, conducted, receiving, median, functional, virological study, cellular and molecular, analyses, depleting, COVID-19 in patient, had more, 【제목키워드】 COVID-19, B-cell, Immunochemotherapy,