Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19

Abstract

Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.

Graphical abstract

Figure 1.

Individual longitudinal evolution before and after CPT. Individual longitudinal evolution of temperature (A), inflammation biomarkers [CRP (B), ferritin (C), IL-6 (D)], and SARS-CoV-2 RT-PCR (E) and viral load assessed using ddPCR (F). (D) IL-6 was assessed in 5 patients at days −5 and +7, considering days 0 and +1 the days of CPT. (F) ddPCR was assessed in 9 patients with a sensitivity threshold of 1.17 log (copies per milliliter), represented by the dashed line. (G) Lymphocyte immunophenotyping (T, natural killer [NK], and B lymphocytes) at baseline was assessed by flow cytometric analysis. The expression of CD3, CD19, and CD16/CD56 was used to quantify T cells, B cells, and natural killer cells, respectively. (H) Quantification of peripheral SARS-CoV-2–specific T lymphocytes in 3 patients (P1, P2, and P3) prior to plasma transfusion. Results are expressed as the number of spot-forming cells (SFC) per million circulating CD3⁺ T lymphocytes. CFX1, positive control peptide pool; COV-S1, Spike glycoprotein S1; COV-S2, Spike glycoprotein S2; NCAP, nucleoprotein; PHA, phytohemagglutinin A (positive control mitogen); VME1, membrane protein.