How Long Does Immunity Last After SARS-CoV-2 Infection in Patients with Hematologic Malignancies?

Preliminary data presented at EHA2021 Virtual, the annual congress of the European Hematology Association, suggest that the duration of antibody-mediated protection against reinfection with SARS-CoV-2 in patients with hematologic disorders is short lived. In addition, researchers observed a low rate of seroconversion in patients treated with rituximab-based therapy at the onset of infection, compared with patients who did not receive rituximab.

Anna Candoni, MD, of the University of Udine in Italy, presented results from the first 38 COVID-19─positive patients with hematologic malignancies enrolled in the study. All patients were tested for humoral response. Participants’ median age was 61 years (range = 21-85). Of the 38 patients, 27 had symptomatic SARS-CoV-2 infection and 11 had mild symptoms. The most common symptoms were fever, sore throat, anosmia, cough, shortness of breath, and fatigue. Eight patients had pneumonia requiring hospitalization and oxygen therapy.

At onset of infection, the median immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) values were 674 mg/dl (range = 167-2,210), 53 mg/dl (range = 6-2,510), and 40 mg/dl (range = 7-605), respectively. Median lymphocytes at onset of infection were 1,100/mmc (range = 250-3,300). None of the patients died from COVID-19.

The underlying hematologic malignancies of patients in the study were:

  • lymphoma (n=14)
  • multiple myeloma (n=8)
  • chronic lymphoproliferative diseases (n=8)
  • acute leukemia (n=4)
  • myelodysplastic syndromes (n=1)
  • paroxysmal nocturnal hemoglobinuria (n=2)
  • immune thrombocytopenia (n=1)

Investigators tested IgM and IgG antibodies against SARS-CoV-2 spike protein (subunit S1 and S2) using chemiluminescence immunoassay with a positive cutoff value of 15 UA/mL. Serum IgM and IgG levels were longitudinally measured at one, two, three, and four months after first positive nasopharyngeal swab test to assess the kinetics of antibody titers.

A total of 30 patients (80%) experienced seroconversion. Seven patients (54%) with non-Hodgkin lymphoma and chronic lymphocytic leukemia had seroconversion, while 92% of patients (n=23) with other hematologic diseases experienced seroconversion. Six of the eight patients without seroconversion were receiving rituximab-based therapy. Among the seven patients who were treated with rituximab at the onset of SARS-CoV-2 infection, all but one had median IgG under the cutoff value.

After a peak of IgG and overall mild increase of IgM, the antibody titer declined from four months after disease onset under the positive cutoff value. However, the authors wrote, variation between patients was detected. Mean and median IgM (AU/mL), respectively, were:

  • month 1: 9.6 and 2.9 (n=38)
  • month 2: 4.7 and 2.4 (n=35)
  • month 3: 4.1 and 1.3 (n=30)
  • month 4: 3.6 and 1 (n=25)
  • month 6: 0.6 and 0.5 (n=24)

Mean and median IgG were:

  • month 1: 51.6 and 32.3 (n=38)
  • month 2: 57.2 and 62.1 (n=35)
  • month 3: 58.8 and 62.7 (n=30)
  • month 4: 50.5 and 54.5 (n=25)
  • month 6: 18.5 and 10.3 (n=24)

“We observed a short-lasting antibody response, which means a short duration of antibody-mediated protection against SARS-CoV-2 reinfection,” said Dr. Candoni.

These findings are limited by the study’s small sample size. “If confirmed in a larger number of cases, these results would [support] maintaining infection prevention and control measures even for hematologic patients who have recovered from COVID-19, particularly in the rituximab setting,” said Dr. Candoni, adding that this population should be vaccinated periodically.

To better understand the duration of overall immunologic response against SARS-CoV-2 in patients with hematologic disorders, “additional studies exploring both humoral and cellular immunity (T cells and memory B cells) will be required,” the authors concluded.

Reference

Candoni A, Pizzano U, Fabris M, et al. Seroconversion and longevity of anti-SARS-CoV-2 antibodies in onco-hematologic patients who experienced SARS-CoV-2 infection. Abstract #S289. Presented at the EHA2021 Virtual Congress, June 9-17, 2021.