Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab

Abstract

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Fig. 1. Longitudinal profile of antibodies against nucleocapsid and spike protein in patients with and without hematological malignancy.

Nucleocapsid antibody (anti-N-Ab) levels and spike antibody (anti-S-Ab) levels were determined at 1 (M1), 3 (M3), and 6 (M6) months after nasal swabs became PCR-negative. The levels of Ab in light units against the nucleocapsid (top two panels) and spike protein (bottom two panels) over time were plotted on the y axis. The mean values of Ab levels are represented by the thick dotted lines. The cutoff values for determining seropositivity for anti-N-Ab and anti-S-Ab are shown by the thin dashed lines.

Fig. 2. Antibody levels against SARS-CoV-2 nucleocapsid and spike protein in hematologic patients with COVID-19.

Antibody levels against SARS-CoV-2 nucleocapsid (NAb) and spike protein (S-Ab) were determined among the follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLCL) compared with patients with other hematological malignancies. Each symbol represents an individual patient sample from 1 (M1), 3 (M3), and 6 (M6) months after nasal swabs became PCR-negative. Antibody levels are plotted in light units (LU) on the y axis and the solid horizontal line represents the mean level for each group. Statistically significant differences in antibody levels among the sample group were determined by a Student’s t test.

Fig. 3. Correlation of antibody levels against SARS-CoV-2 nucleocapsid and spike protein with patient severity.

Antibody levels against SARS-CoV-2 nucleocapsid (N-Ab) and spike protein (S-Ab) were determined in the hematological cohort based on the clinical severity scale, severe vs non-severe, based on the criteria described in the material and methods. Each symbol represents an individual patient sample from a given timepoint. Antibody levels are plotted in light units on the y axis and the solid horizontal line represents the mean level for each group. Statistically significant differences in antibody levels among the sample group were determined by a Student’s t test.

Fig. 4. Antibody levels against SARS-CoV-2 nucleocapsid and spike proteins in patients receiving prior or ongoing Rituximab treatment.

Antibody levels against SARS-CoV-2 nucleocapsid (N-Ab) and spike protein (S-Ab) were determined in hematological patients receiving prior or ongoing Rituximab treatment. Comparison of antibody levels in these two groups was determined at 1 (M1), 3 (M3), and 6 (M6) months after nasal swabs became PCR-negative. Statistically significant differences in antibody levels among the sample group were determined by a Student’s t test.

Fig. 5. Longitudinal profile of antibodies against the spike protein in hematological patients receiving prior or ongoing rituximab treatment.

Spike antibody (S-Ab) levels were determined at 1, 3, and 6 months after nasal swabs became PCR-negative in hematological patients receiving prior (a) or ongoing rituximab treatment (b). The cutoff value for determining seropositivity for S-Ab is shown by the dotted lines.