COVID-19 Breakthrough Infections in Severely Immunocompromised Patients Who Received Tixagevimab/Cilgavimab for Pre-exposure Prophylaxis

Background Immunocompromised patients who do not respond to vaccination are at increased risk of SARS-CoV-2 infections, including hospitalization and death. Tixagevimab/cilgavimab is a monoclonal antibody combination that has been shown to reduce the risk of SARS-CoV-2 infection. We aimed to assess the incidence and outcomes of COVID-19 among severely immunocompromised patients who received tixagevimab/cilgavimab for pre-exposure prophylaxis (PrEP) during the period when the Omicron variant was the dominant circulating variant. Methods We conducted a retrospective cohort study of vaccinated, severely immunocompromised adults who received at least 1 dose of tixagevimab/cilgavimab for SARS-CoV-2 PrEP. The study specifically evaluated those who did not mount an immune response to vaccination, as indicated by a negative anti-spike immunoglobulin G. Results Seventy-one patients (20.3%) developed breakthrough COVID-19 after tixagevimab/cilgavimab administration. Among patients who developed breakthrough infection with COVID-19, 70 (98.6%) had mild disease and were treated as outpatients. Conclusion Our study suggests that tixagevimab/cilgavimab may be efficacious for vaccinated severely immunocompromised patients. Developing a universal vaccine and other long-acting monoclonal antibodies for PrEP in immunocompromised patients against all SARS-CoV-2 variants, as well as potential emerging coronaviruses, holds promise for combating future outbreaks.