Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients—authors’ response

We appreciate the opportunity to respond to the comments of Dr Barone and colleagues1 regarding our manuscript ‘Suboptimal response to combination therapy with tixagevimab/cilgavimab and remdesivir for persistent SARS-CoV-2 infections in immunocompromised patients’.2 During the SARS-CoV-2 pandemic, selection of an appropriate therapeutic mAb in the context of emerging SARS-CoV-2 variants was challenging. One reason is that clinical trials may not provide real-time evidence for clinical efficacy of a specific mAb under emergency use authorization (EUA) as the circulating variants at that time are commonly different from those in the trial stage. Besides, new variants may accumulate key resistance mutations in the spike protein and confer reduced neutralization by a specific mAb. Further, the implementation of commercial diagnostics for variant detection to guide precision therapy of SARS-CoV-2 in routine laboratory workflows is limited by turnaround times, costs and manpower. Therefore, the recommendations for early administration of a specific mAb for at-risk COVID-19 patients largely depend on local epidemiology of circulating SARS-CoV-2 variants and their in vitro neutralization by the selected mAb.3,4