Examining Immune Response in Patients with Hematologic Malignancy After COVID-19 Infection

Patients with a history of a hematologic malignancy who survive COVID-19 infection have similar immune responses against the virus following infection compared with people without blood cancers, according to an analysis presented at the 2020 ASH Annual Meeting. However, those diagnosed with non-Hodgkin lymphoma (NHL) who are receiving rituximab appear to have lower rates of seroconversion and anti–SARS-CoV-2 antibody levels, the authors, led by Chiara Cattaneo, MD, from ASST Spedali Civili di Brescia in Italy, reported.

To determine the long-term prognosis and persistence of specific immune responses among those who survive acute COVID-19 infection, Dr. Cattaneo and researchers monitored clinical outcomes and antibody responses to SARS-CoV-2 during convalescence in patients with hematologic diseases. The researchers also evaluated antibody levels and clinical outcomes in 14 control patients without hematologic disorders who had survived COVID-19.

The study group included 51 patients with multiple myeloma (MM), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), other chronic lymphoproliferative disorders (CLD) including chronic lymphocytic leukemia, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MDS/MPN).

Patients were followed longitudinally starting one month after the documentation of a negative SARS-CoV-2 nasal swab and immune responses were evaluated at one, three, six, nine, and 12 months. Antibodies to different conformations of the COVID-19 virus proteins nucleocapsid (N) and spike (S) were measured using a highly sensitive luciferase-immunoprecipitation system (LIPS) assay.

Of the 51 eligible patients, 41 were tested for SARS-CoV-2 antibodies at one month after a negative nasal swab, and nine patients also had testing at three months.

At the time of COVID-19 diagnosis, four patients (10%) had been newly diagnosed with a hematologic disease, 16 (39%) had disease in complete or partial remission, six (15%) had relapsed/refractory disease, and 15 (36%) had stable disease. Half of patients were on active treatment.

The median time from SARS-CoV-2 detection to swab negativity was 30 days (range = 8-63), and this was not influenced by sex, age, hematologic disease, disease status, or treatment received. However, the researchers reported that two patients remained swab-positive at 119 and 123 days – both of whom had DLBCL secondary to FL.

At one month, antibody levels were similar in hematologic patients and controls, while rates of N and S seropositivity were slightly lower in patients with blood diseases, compared with controls:

  • nucleocapsid protein seropositivity: 30/41 (73%) vs. 13/14 (93%)
  • spike protein seropositivity: 27/41 (66%) vs. 13/14 (93%)

Seven patients (17%) had discrepancies between N and S seropositivity, all of whom had lymphoid disorders.

The researchers found that seroconversion rates and antibody levels did not appear to be influenced by age, sex, or disease status. Ongoing treatment, time to swab negativity, severity of pneumonia, and steroid treatment during acute COVID-19 infection also did not affect seroconversion rates or antibody levels.

However, they observed that patients who were diagnosed with NHL had lower rates of seroconversion and antibody levels, for both N and S proteins. In the 15 patients with NHL, the N seropositivity rate was 47%, compared with 92% in the 26 other hematologic patients (p=0.002). The S seropositivity rate was 40%, compared with 85% (p=0.0053).

Thirteen of the 15 patients with NHL were treated with rituximab, and ongoing rituximab treatment had a negative effect specifically on S protein antibody production. “While N protein seroconversion and antibody levels were not influenced, none of the six patients on ongoing rituximab had S protein seroconversion, versus five of the seven patients with past rituximab use,” the study authors reported.

There was no significant variation between anti-N or anti-S antibody levels at the one- and three-month measurements. Also, at three months, seroconversion status was maintained by all study patients and controls. The only patient with antibody levels below the cutoff at one month did not show seroconversion at three months, the investigators added.

Overall, patients with hematologic malignancies who survived COVID-19 infection have COVID-19 protein antibody levels and seroconversion rates similar to controls without hematologic disorders, although time to swab negativity was more similar to that of critically ill patients than in the general population.

Study authors report no relevant conflicts of interest.

Reference

Cattaneo C, Cancelli V, Pagani C, et al. Longitudinal serological response to Sars-COV-2 in patients affected by hematologic diseases. Abstract #2651. Presented at the 2020 American Society of Hematology Annual Meeting, December 7, 2020.