Tixagevimab-Cilgavimab Preexposure Prophylaxis in Solid Organ Transplant Recipients Is Associated With Fewer Breakthrough SARS-CoV-2 Infections, Except During the BA.5 Period.

Tixagevimab–cilgavimab preexposure prophylaxis (PreP) was associated with a lower risk of breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated solid organ transplant recipients (SOTRs) during the early Omicron period, when the B.1.1.529, BA.2, and BA.2.12.1 lineages were most prevalent.1 Since then, in vitro studies have shown reduced neutralization of the BA.5 lineage by tixagevimab– cilgavimab.2 In this study, we aimed to evaluate the realworld effectiveness of tixagevimab–cilgavimab against the BA.5 lineage.

We extended our prior retrospective multicenter cohort study1 to include all SOTRs at our institutions who received their first tixagevimab–cilgavimab dose between December 28, 2021, and June 30, 2022. A control group of age-matched SOTRs who did not receive tixagevimab– cilgavimab was used for comparison. The primary outcome was the development of any breakthrough SARS-CoV-2 infection during the period of BA.5 predominance, defined as a newly positive SARS-CoV-2 antigen or polymerase chain reaction test between July 2, 2022, and November 4, 2022, performed for symptoms or other indications.

Six hundred thirty-three SOTRs received tixagevimab– cilgavimab at our institutions between December 28, 2021, and June 30, 2022. Baseline characteristics were similar between the tixagevimab–cilgavimab and control groups, except for a higher proportion of SOTRs with a history of prior SARS-CoV-2 infection, a higher rate of unvaccinated individuals, a lower proportion of lung transplant recipients, and a longer time since transplantation in the control group (Table 1).

Univariable and multivariable analyses showed that tixagevimab–cilgavimab PreP was associated with a lower risk of developing any breakthrough SARS-CoV-2 infection (unadjusted hazard ratio [HR] = 0.73; 95% confidence interval [CI], 0.57-0.95 and adjusted HR [aHR] = 0.62; 95% CI, 0.47-0.83, respectively; Figure 1A and B). There was no significant association between tixagevimab–cilgavimab PreP and breakthrough SARS-CoV-2 infection resulting in hospitalization or death in univariable (unadjusted HR = 0.56; 95% CI, 0.28-1.11; Figure 1C) or multivariable analysis (aHR = 0.57; 95% CI, 0.28- 1.15; Figure 1D). Multivariable analysis also showed that additional vaccine doses (aHR = 0.76 for each additional vaccine dose; 95% CI, 0.61-0.95) and prior SARS-CoV-2 infection (aHR = 0.28; 95% CI, 0.09-0.92) were associated with a significantly lower risk of hospitalization or death from SARS-CoV-2 infection. During the BA.5 period, there was no significant association between tixagevimab–cilgavimab PreP and the incidence of breakthrough SARS-CoV-2 infection.