Seroconversion and longevity of anti SARSCOV- 2 antibodies in ONCO-hematologic patients WHO experienced SARS-COV-2 infection

Background: Data on the dynamics and duration of immune response to SARS-CoV-2 infection in hematologic patients are still lacking. Preliminary studies, in non immunocompromised subjects with COVID- 19, reported that seroconversion was observed 7 to 14 days following symptom onset with an increase of the IgM and IgG titers during the first month. IgM levels, after peaking by day 30, gradually decreased and can be undetectable by day 180 post-onset. The long-lasting persistence of IgG is not clearly confirmed. Aims: We evaluate the seroconversion and the kinetics of IgM and IgG against SARS-CoV-2 in hematologic patients who were followed after reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmation of SARS-CoV-2 infection. Methods: Here we report the preliminary data regarding the first 25 COVID-19 positive hematologic patients that were tested for humoral response. The median age was 59 years (range 21-85). The underling hematologic diseases were: lymphoma (10/25), myeloma (7/25), chronic lymphoproliferative diseases (5/25) and acute leukemia (3/25). SARSCoV- 2 infection was mild symptomatic in 5/25 cases and symptomatic in 20/25. Four of these 20 patients had pneumonia that required hospitalization. The median value of IgG, IgM and IgA, at onset of the SARS-CoV-2 infection, was 832 mg/dl (167-2210), 54,5 mg/dl (6-2510) and 54 mg/dl (8-605), respectively. The median value of lymphocytes was 1100/mmc (250-3300). The IgM and IgG antibodies against SARSCoV- 2 spike protein (subunity S1 and S2) were tested by chemiluminescence immunoassay (CLIA) with a positive cut-off value of 15 UA/ ml for both IgG and IgM. To assess the kinetics of antibody titers, in our convalescent COVID-19 patients, serum IgM and IgG levels were longitudinally measured at established time points: one month (T1) two months (T2), three months (T3) and four months (T4) after their first positive nasopharyngeal swab test. Results: Among these first 25 COVID-19 cases, 21/25 (84%) developed specific anti SARS-CoV-2 antibodies with a titer > 15 UA/ml in almost one of the specific time points. However, as reported in Figure A and B, after a peak of the IgG and an overall mild increase of IgM, the antibody titer declined from 4 months after the disease onset under the positive cut-off value, although variation between patients was detected. In detail the mean and median titers were: 1) at T1: 56 UA/ml and 75,5 UA/ml for IgG, 15 UA/ml and 6 UI/ml for IgM;2) at T2: 68 UA/ml and 73 UA/ ml for IgG, 7 UA/ml and 2,6 UA/ml for IgM;3) at T3: 54 UA/ml and 55 UA/ml for IgG and 5 UA/ml and 1,35 UA/ml for IgM;4) at T4: 7 UA/ml and 5,3 UA/ml for IgG and 0,2 UA/ml and 0,2 UA/ml for IgM. Summary/Conclusion: Although the number of patients is still limited, our preliminary results show a short lifespan of antibody response in hematologic patients, suggesting a short duration of antibody-mediated protection against re-infection with SARS-CoV-2. If confirmed in a larger number of cases, these results would suggest to maintain infection prevention and control measures even for hematologic patients who have recovered from COVID-19. In addition, this population should get vaccinated periodically. Additional studies, exploring both humoral and cellular immunity (T cells and memory B cells), will be require to better understand the overall immunologic response against SARS-CoV-2 (and its duration) in hematologic patients.