Improved outcomes in patients with chronic lymphocytic leukaemia infected during the omicron BA.5 subvariant surge.

Patients with chronic lymphocytic leukaemia (CLL) infected with SARS-CoV-2 are at increased risk of severe COVID-19 and death. The outcomes of CLL patients with COVID-19 during the omicron subvariants and in particular with BA.5 are not fully elucidated. Here, we report the outcomes of 128 CLL patients diagnosed with COVID-19 from December 2021 through November 2022. The hospitalization and 30-day mortality rates were 26.6% (n = 34) and 4.7% (n = 6), respectively. Both hospitalizations and mortality were lower during the outbreaks of the BA.2 and BA.5 subvariants (17.2%, 0% vs. 15.2%, 0%, respectively) compared with the period dominated by the BA.1 subvariant (41.5%, 11.3%).

REGEN-COV antibody combination in patients with lymphoproliferative malignancies and SARS-CoV-2 infection.

Patients with lymphoproliferative diseases are at high risk for SARS-CoV-2-related complications and mortality. The role of casirivimab and imdevimab (REGEN-COV), a neutralizing antibody cocktail, to treat immunocompromised hemato-oncological patients with SARS-CoV-2 disease 2019 (Covid-19) remains unknown. Here, we present our clinical experience on the outcome of 15 hematological patients treated with REGEN-COV for SARS-CoV-2 infection. Most patients failed to respond or achieved low antibody titer after 2-3 doses of BNT162b2 mRNA vaccine. All patients experienced clinical improvement with no mortality within a median follow-up of 70 days. In conclusion, early administration of REGEN-COV to high-risk hematological patients may prevent clinical deterioration and mortality from SARS-CoV-2 infection. The effectiveness of neutralizing antibodies may vary depending on the virus variants and in particular with the omicron variant (B.1.1.529).

Association of a Third Dose of BNT162b2 Vaccine With Incidence of SARS-CoV-2 Infection Among Health Care Workers in Israel.

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 Participants: This 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 Measures: The 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.

Evolution of spike mutations following antibody treatment in two immunocompromised patients with persistent COVID-19 infection.

Immunocompromised patients have an increased risk of persistent COVID-19 disease. We report here the clinical course of two patients with hematologic malignancies hospitalized due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In both patients, viral evolution including new spike gene mutations that occurred following treatment with anti-SARS-CoV-2 antibodies preparations, including convalescent plasma and bamlanivimab. These cases demonstrate the possibility of antibody-resistant SARS-CoV-2 infections evolution in immunocompromised patients.

Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy control subjects. Patients received 2 vaccine doses, 21 days apart, and antibody titers were measured by using the Elecsys Anti-SARS-CoV-2 S 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 control subjects revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). The response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients and 16.0% in patients under treatment at the time of vaccination. In patients treated with either Bruton's tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%). None of the patients exposed to anti-CD20 antibodies <12 months before vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, female sex, lack of currently active treatment, immunoglobulin G levels ≥550 mg/dL, and immunoglobulin M levels ≥40 mg/dL. In conclusion, antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment. This trial was registered at www.clinicaltrials.gov as #NCT04746092.

Characteristics and Outcomes of Patients Infected with SARS-CoV-2 in Israel: Correlation between Laboratory Findings on Admission to Emergency Department and Subsequent Respiratory Failure.

BACKGROUND: There is limited clinical information on coronavirus disease-19 (COVID-19) patients in Israel. OBJECTIVES: To describe the characteristics, outcomes, and potential associations of hospitalized COVID-19 patients in Israel. METHODS: We conducted a single-center, retrospective study of 58 consecutive laboratory-confirmed COVID-19 patients admitted to Laniado Hospital, Israel, between 14 March 2020 and 14 May 2020. Demographic, clinical, and laboratory data on admission were collected and analyzed, and the association to subsequent respiratory failure was assessed. RESULTS: Mean age of patients was 70.7 ± 16.9 years (53% males, 47% females.); 74% had at least one co-morbidity. Most patients were of Jewish Ashkenazi descent. During hospitalization 15 patients (mean age 78.18 ± 10.35 years); 80% male, 73% Sephardi descent developed respiratory failure rates of 60% occurring on average 10.6 days following intubation. Laboratory tests at admission displayed a significant increase in C-reactive protein (CRP) and creatine kinase (CK) and a decrease in absolute lymphocyte count (ALC) in patients who eventually developed respiratory failure (163.97 mg/L, 340.87 IU/L, 0.886 K/µl vs. 50.01 mg/L and 123.56 IU/L, 1.28 K/µl, respectively). Multivariate logistic analysis revealed an integrated parameter of CRP, CK, and ALC highly correlated with respiratory failure. Receiver operating characteristic curve revealed the area under the curve of CRP, CK, and ALC and the integrated parameter to be 0.910, 0.784, and 0.754, respectively. CRP was the strongest predictor to correlate with respiratory failure. CONCLUSIONS: CRP, CK, and ALC levels on admission could possibly be used to detect high-risk patients prone to develop respiratory failure.