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. [ABSTRACT FROM AUTHOR]