Breakthrough SARS-CoV-2 Infections Among Recipients of Tixagevimab-cilgavimab Prophylaxis: A Citywide Real-world Effectiveness Study

There are limited real-world data on the effectiveness of tixagevimab-cilgavimab as pre-exposure prophylaxis of COVID-19. We describe lessons learned when coordinating data collection and identifying breakthrough SARS-CoV-2 infections among patients across indications and institutions in a major US city. The Chicago Department of Public Health requested patient-level tixagevimab-cilgavimab administration data from all prescribing providers in Chicago, for treatments December 8, 2021 through June 30, 2022. Records were matched to COVID-19 vaccinations and laboratory-confirmed SARS-CoV-2 infections through December 31, 2022. Due to difficulty collecting data from all providers, targeted follow-up was conducted to improve completeness on key variables (demographics, vaccination status, clinical indication for prophylaxis). Over half of reported tixagevimab-cilgavimab administrations were to patients residing outside Chicago. Five hundred forty-four Chicago residents who received at least one dose of tixagevimab-cilgavimab were included in this analysis. Most were age 50 years or older (72%), Black non-Latinx (33%) or White non-Latinx (29%), and fully vaccinated (80%). Seventy-five patients (14%) had laboratory-confirmed COVID-19. Patients with and without breakthrough infections were demographically similar. Clinical indication was missing for >95% of cases, improved to 64% after follow-up; the most frequently specified was hematologic malignancy (10%). Severe outcomes were uncommon: 16% had documented COVID-19-related hospitalizations, one death was identified. Tixagevimab-cilgavimab recipients in Chicago had a lower rate of severe SARS-CoV-2 infection than reported among other untreated high-risk patients, including during predominance of non-neutralizing variants. Improving stakeholder collaboration is essential for generation of real-world effectiveness data, informing pandemic preparedness and optimizing use of medical countermeasures.