key: cord-0729078-ke3z221h authors: Tadmor, Tamar; Benjamini, Ohad; Braester, Andrei; Rahav, Galia; Rokach, Lior title: Antibody persistence 100 days following the second dose of BNT162b mRNA Covid19 vaccine in patients with chronic lymphocytic leukemia date: 2021-08-10 journal: Leukemia DOI: 10.1038/s41375-021-01380-5 sha: 9996a4e9d079e51ac085420b897cb323c7fce0c2 doc_id: 729078 cord_uid: ke3z221h nan signed-rank test. In all cases, the significance level was set at 5%, and a result was considered significant if the estimated p value (p) was below the significance level. As in the study by Rose et al. [6] the antibody decay rates, and half-life were calculated using an exponential model described in detail in supplement data (Supplementary Table 1) . Of the 49 (58%) patients who tested positive in the first serology test, 36 (73%) maintained their positive status (Fig. 1a) . On the other hand, of 35 (42%) patients who had tested negative in the first serology test, two patients (6%) developed sufficient antibodies to be considered positive in the second test. (Fig. 1b-d) . When we compared our calculated decay of IgG levels in patients with CLL (provided they were tested positive in the first serology test), to that published in healthy controls [6] , we observed that the decay among patients with CLL is comparable to the decay reported for healthy controls that are 70 years old or older. Nevertheless, since patients with CLL tend to demonstrate lower IgG titer all along, it should be noted that 27% of the patients (13 out of 49) had titer values below the required threshold to be considered positive (RBD-IgG titer value greater than 50 U/mL is considered positive). In contrast, none of the healthy adults has titer values below the threshold even after 209 days [6] . Table 1 summarizes the clinical and demographic characteristics of the patients studied and their corresponding results in terms of positive/negative rate and the titer values (in log scale). Additional demographic data are available in Supplementary Table 2 . We feel that special attention should be paid to the three patients who had increased their antibodies levels in the second test following the vaccine. Two of them have switched from a negative to a positive status. Both patients are male that were previously treated with anti-CD20 Ab (12 and 120 months ago). The third patient is a treatment-naive male whose titer values increased from 143 (positive borderline) in the first test to 323 in the second test. The table summarizes also the vaccine response according to therapy status. Therapy naive patients yield the highest response rate (76.2% and 61.9% in the first and second test, respectively) followed by previously treated patients (61.9% and 52.4% in the first and second test, respectively). A clear drop in the measured titer values is seen virtually across all therapy groups. We had 22 patients (26.2%) who achieved complete response (CR) following therapy for their disease. 6/22 (27.2%) developed positive Vaccine Response Rate in Test 1 and in all 6 patients positive response was maintained. Taken together our longer follow-up, we can summarize that treatment-naive patients or those achieving CR post therapy are those who may best benefit from vaccination. Of note, at the time of writing this letter, none of the patients have developed Covid-19 infection following vaccination. We observed four factors associated with the inability to sustain IgG levels above the threshold: patients still receiving therapy for their disease (odds ratio of 0.2987), patients who developed adverse side effects to the vaccine (odds ratio 0.3598), female gender (odds ratio of 0.4231) and having IgM levels below 40 mg/dL during the first serology test (odds ratio of 0.4481). We need to emphasize that it is necessary to take our reported results with caution and remember that the FDA and other organizations recommend not using seroconversion levels after SARS-Cov2 vaccination to measure its effectiveness nor modifying preventive measures (FDA May 2021) (https://www.fda.gov/medicaldevices/safety-communications/antibody-testing-not-currentlyrecommended-assess-immunity-after-covid-19-vaccination-fdasafety). Indeed, the exact value of antibody titer is still waiting for a longer follow-up and further studies. In conclusion, this is the first longitudinally report of patients with CLL who received BNT162b mRNA Covid19 vaccine. We demonstrated that after a median of 100 days, decay of IgG levels is similar to that of the elderly healthy controls indicating that although the amount of produced antibodies is lower, patients who respond to the vaccine are able to maintain their immune response. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19 Durability of responses after SARS-CoV-2 mRNA-1273 vaccination Multicenter nationwide comparison of seven serology assays reveals a SARS-CoV-2 nonresponding seronegative subpopulation LR designed the study and wrote the letter. TT, OB, AB and GR contribute patient's data. LR performed statistical analysis 4 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. 5 Department of Hematology, Galilee Medical Center, Nahariya, Israel. 6 The Infectious Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel. 7 Department of Software and Information Systems Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 8 These authors contributed equally: Tamar Tadmor and Ohad Benjamini. ✉ email: Tamar.tadmor@b-zion.org.il The authors declare no competing interests. Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41375-021-01380-5.Correspondence and requests for materials should be addressed to O.B.Reprints and permission information is available at http://www.nature.com/ reprintsPublisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.