Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study (NCT04746092) was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to BNT162b2 mRNA COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy controls. Patients received two vaccine doses, 21 days apart, and antibody titers were measured using Elecsys® Anti-SARS-CoV-2S assay after administration of the second dose. In a total of 167 patients with CLL the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy controls, revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio=0.010, 95% CI 0.001-0.162; p<0.001). Response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naïve and 16% only in patients under treatment at the time of vaccination. In patients treated with either BTK inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%, respectively). None of the patients exposed to anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, females, lack of currently active treatment, IgG levels ≥550 mg/dL and IgM levels ≥40mg/dL. In conclusion, antibody-mediated response to BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment.

IMPORTANCE Administration of a BNT162b2 booster dose (Pfizer-BioNTech) to fully vaccinated individuals aged 60 years and older was significantly associated with lower risk of SARS-CoV-2 infection and severe illness. Data are lacking on the effectiveness of booster doses for younger individuals and health care workers.OBJECTIVE To estimate the association of a BNT162b2 booster dose with SARS-CoV-2 infections among health care workers who were previously vaccinated with a 2-dose series of BNT162b2. DESIGN, SETTING, AND PARTICIPANTSThis was a prospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. The study cohort included 1928 immunocompetent health care workers who were previously vaccinated with a 2-dose series of BNT162b2, and had enrolled between August 8 and 19, 2021, with final follow-up reported through September 20, 2021. Screening for SARS-CoV-2 infection was performed every 14 days. Anti-spike protein receptor binding domain IgG titers were determined at baseline and 1 month after enrollment. Cox regression with time-dependent analysis was used to estimate hazard ratios of SARS-CoV-2 infection between booster-immunized status and 2-dose vaccinated (booster-nonimmunized) status.EXPOSURES Vaccination with a booster dose of BNT162b2 vaccine. MAIN OUTCOMES AND MEASURESThe primary outcome was SARS-CoV-2 infection, as confirmed by reverse transcriptase-polymerase chain reaction. RESULTS Among 1928 participants, the median age was 44 years (IQR, 36-52 years) and 1381 were women (71.6%). Participants completed the 2-dose vaccination series a median of 210 days (IQR, 205-213 days) before study enrollment. A total of 1650 participants (85.6%) received the booster dose. During a median follow-up of 39 days (IQR, 35-41 days), SARS-CoV-2 infection occurred in 44 participants (incidence rate, 60.2 per 100 000 person-days); 31 (70.5%) were symptomatic. Five SARS-CoV-2 infections occurred in booster-immunized participants and 39 in booster-nonimmunized participants (incidence rate, 12.8 vs 116 per 100 000 person-days, respectively). In a time-dependent Cox regression analysis, the adjusted hazard ratio of SARS-CoV-2 infection for booster-immunized vs booster-nonimmunized participants was 0.07 (95% CI, 0.02-0.20).CONCLUSIONS AND RELEVANCE Among health care workers at a single center in Israel who were previously vaccinated with a 2-dose series of BNT162b2, administration of a booster dose compared with not receiving one was associated with a significantly lower rate of SARS-CoV-2 infection over a median of 39 days of follow-up. Ongoing surveillance is required to assess durability of the findings.

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to COVID-19 vaccination. Here, we evaluated SARS-CoV-2S antibody persistence at 6 months after a two-dose regimen of BNT162b2 COVID-19 vaccine in patients with CLL/small lymphocytic lymphoma (SLL) and healthy controls who had a documented initial response, 2-3 weeks after the second vaccine dose. In a total of 61 patients with CLL/SLL and 39 controls, antibodies were still detectable in 90.2% (n555) of the patients compared to 100% (n539) of the controls (adjusted odds ratio50.11, 95% CI 0.11-1.98; p50.079). Antibody titers decreased significantly overtime in both patients [from a median of 107.1 U/ mL (interquartile range (IQR), 4.6-672.6) to 67.5 U/mL (IQR, 8.0-203.6), p50.003] and controls [from a median of 983.2 U/mL (IQR, 610.9-1649.0) to 232.9 U/mL (IQR, 157.7-534.1), p,0.001]. Patients on active treatment (n514) had the lowest seropositivity rate (64.3%) and antibody titers [median52.8, (IQR, 0.5-17.6)]. Seronegativity occurred in 6 patients; 5 of them continued or initiated treatment during follow-up.In summary, the vast majority of patients with CLL/SLL who initially responded to COVID-19 vaccination remained seropositive at 6 months follow-up. However, antibody titers decreased significantly overtime and low titers or complete antibody loss were associated with active treatment. Patients with chronic lymphocytic leukemia (CLL) have increased risk for severe coronavirus disease 2019 (COVID-19) as well as mortality. 1,2 We and others have reported that patients with CLL/small lymphocytic lymphoma (SLL) have an impaired antibody response to COVID-19 vaccination. 3,4 Understanding the long-term persistence of SARS-CoV-2 antibodies after vaccination is highly important to ensure an appropriate vaccination strategy. COVID-19 messenger RNA (mRNA)-based vaccination in healthy subjects has been reported to elicit antibody response that persists for at least 6 months after the second vaccine dose 5 ; however, the durability of humoral response in patients with CLL/SLL is still unknown. Here, we report an updated analysis of our primary cohort that now focuses on antibody persistence after a 2-dose regimen of BNT162b2 COVID-19 vaccine in patients with CLL/SLL. This prospective study was conducted in the framework of the European Research Initiative on CLL. The study was approved by the institutional review board and is registered in ClinicalTrials.gov (no. NCT04746092). All subjects provided informed consent. Eligibility criteria for the study included diagnosis of CLL/SLL according to the International Workshop on Chronic Lymphocytic Leukemia criteria, 6 age 18 years or older, with no known history of SARS-CoV-2 infection. The study has also included healthy volunteers that served as a control group. Patients and healthy controls who participated in the primary cohort 3 and achieved a serologic response, 2 to 3 weeks after the second vaccine dose, were reevaluated for antibody persistence at 6 months after vaccination. Serum sampl...

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