Immune Modulation and Efficacy of Tixagevimab/Cilgavimab Pre-Exposure Prophylaxis in Lung Transplant Recipients During the Omicron Wave

Lung transplant recipients are at increased risk of severe COVID-19 due to lifelong immunosuppressive therapy, which impairs both innate and adaptive immune responses. Identifying effective supportive therapies is essential for mitigating the heightened vulnerability of this population. This study investigated the effects of tixagevimab/cilgavimab, a monoclonal antibody therapy, as pre-exposure prophylaxis (PrEP) in this population. A prospective study was conducted on 19 lung transplant recipients at Padua University Hospital, Italy, during the Omicron variant wave (May-June 2022). Participants received tixagevimab/cilgavimab intramuscularly and were monitored for 180 days. SARS-CoV-2-specific antibody levels were measured at baseline (T0), one month (T1), and three months (T3) post-treatment. Cytokine profiles and clinical outcomes, including SARS-CoV-2 infections, were also assessed. At baseline, 50% of patients had negative antibody responses, but one-month post-treatment, all patients exceeded 700 kBAU/mL (median 3870 kBAU/mL), with levels decreasing but remaining positive at three months (median 1670 kBAU/mL). Remarkably, a higher level of circulating IL-18 was found at T3 in comparison to T0 in patients who did not experience COVID-19 after PrEP. This finding aligns with IL-18's primary role in stimulating type-1 T helper (Th1) cell responses, necessary for the induction of virus-specific cytotoxic T lymphocytes (CTLs). These results suggest that tixagevimab/cilgavimab may induce a systemic immune signature that could contribute to priming the immune response against SARS-CoV-2, potentially mediated by interactions with immune cell subsets.