Efficacy of Tixagevimab/Cilgavimab as Pre-Exposure Prophylaxis against Infection from SARS-CoV-2 and Severe COVID-19 among Heavily Immunocompromised Patients: A Single-Center, Prospective, Real-World Study

Background: COVID-19 continues to pose a threat to immunocompromised individuals, even with vaccination. The monoclonal antibodies (mAbs) tixagevimab/cilgavimab (TXG/CIL) provide targeted prophylaxis against SARS-CoV-2 with the benefit of a prolonged half-life. Although approved for COVID-19 prevention, there is limited data on their effectiveness among heavily immunocompromised populations. Methods: We conducted a prospective, observational study at Laiko General Hospital, Athens, Greece, from August to December 2022 to investigate the efficacy of TXG/CIL as a form of pre-exposure prophylaxis in immunocompromised patients. Data on breakthrough SARS-CoV-2 infections were collected over a six-month follow-up period. Results: Of the 375 participants (mean age 61.3 +/- 14.1 years; 59.7% male), 76 (20.3%) developed breakthrough SARS-CoV-2 infections, with an incidence of 3.81 cases/100 patient months. Hospitalization was required for 21 patients (5.6%), with a median stay of 14 days. Seven deaths were recorded, with only one attributed to COVID-19. Previous infection (OR 0.46, 95% CI 0.26-0.82) and hybrid immunity (OR 0.52, 95% CI 0.29-0.92) can protect against new infection. Solid organ malignancy significantly increased the risk of severe outcomes among those infected (OR 7.4, 95% CI 2.2-24.7, p = 0.001). Conclusions: TXG/CIL provides effective prophylaxis against COVID-19 in immunocompromised patients. Future strategies should focus on developing new mAb combinations to address emerging SARS-CoV-2 variants and protect vulnerable populations.