We used a self-reporting system to compare symptom frequency of hospital personnel with coronavirus disease 2019 before and after the emergence of the Omicron variant. Omicron was more likely to result in asymptomatic carriage (7% vs 12%; P = .009), and fewer symptoms were observed in those with booster vaccination.
AZD7442 (tixagevimab-cilgavimab) is a combination of two human monoclonal antibodies for preexposure prophylaxis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among highrisk patients who do not mount a reliable vaccine response. Foremost among these are hematologic malignancy patients with limited clinical trial or real-world experience to assess the effectiveness of this combination treatment since the emergence of Omicron and its subvariants. We performed a retrospective study of 892 highrisk hematologic malignancy patients who received AZD7442 at Memorial Sloan Kettering Cancer Center in New York City from January 1, 2022 to July 31, 2022. We evaluated demographic, clinical, and laboratory characteristics and performed regression analyses to evaluate risk factors for breakthrough infection. We also evaluated the impact of updated AZD7442 dosing regimens on the risk of breakthrough infection. Among 892 patients, 98 (10.9%) had a breakthrough infection during the study period. A majority received early outpatient treatment (82%) and eventually eight (8.2%) required hospitalization for management of Coronavirus Disease 2019 (COVID-19), with a single instance of severe COVID-19 and death. Patients who received a repeat dose or a higher first-time dose of AZD7442 had a lower incidence of breakthrough infection. Univariate analyses did not reveal any significant predictors of breakthrough infection. While AZD7442 is effective at reducing SARS-CoV-2 breakthrough infection in patients with hematologic malignancies, no risk factors reliably predicted risk of infection. Patients who received updated dosing regimens as per Food and Drug Administration guidelines had better protection against breakthrough infection.
Background
Sotrovimab is an anti-spike neutralization monoclonal antibody (mAB) developed to reduce the risk of Coronavirus Disease 2019 (COVID-19) progression and advancement to hospitalization in high-risk patients. Currently, there is limited research describing the association of sotrovimab treatment in patients with hematologic malignancies (HM) and the predictive factors of hospitalization.
Methods
We performed an observational study of 156 consecutive cancer patients who received sotrovimab at Memorial Sloan Kettering Cancer Center in New York City during the BA.1 Omicron surge. We evaluated the demographic, clinical, and laboratory characteristics of the patients who had subsequent COVID-19-related hospitalization(s) compared to those who did not.
Results
Among the 156 study patients, seventeen (17, 11%) were hospitalized of which four were readmitted for COVID-19-related complications; three deaths were attributed to COVID-19. Results from multivariable logistic regression show significant factors associated with hospitalization include patients on anti-CD20 therapy (adjusted OR = 5.59, 95% CI (1.73 - 18.12), p = 0.004) and with relapse/refractory disease (adjusted OR = 5.69, 95% CI (1.69 - 19.16), p = 0.005). Additionally, whole-genome sequencing of SARS-CoV-2 detected high occurrences of mutations in the spike gene associated with treatment-related resistance longitudinal samples from 11 patients treated with sotrovimab.
Conclusions
While sotrovimab is effective at reducing COVID-19 hospitalization and disease severity in HM patients when administered early, patients who received anti-CD20 antibodies showed substantial morbidity. Due to the high potential for resistance mutation to sotrovimab and increased morbidity in patients on anti-CD20 therapy, combination treatment should be explored to determine whether it provides added benefits compared to monotherapy.
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