SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients-A Single-Center Experience

Abstract

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on the use of tixagevimab/cilgavimab and sotrovimab as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PrEP in immunocompromised patients, comparing the evolution of antibody levels and reporting the incidence of breakthrough infections. A retrospective, single-center analysis was conducted including 132 immunocompromised patients with inadequate vaccine response, who received COVID-PrEP at our clinic between January and June 2022. Initially, 95 patients received sotrovimab while 37 patients received tixagevimab/cilgavimab. Antibody levels after first PrEP with sotrovimab remain high for several months after infusion (median 10,058 and 7235 BAU/mL after 1 and 3 months, respectively), with higher titers than after tixagevimab/cilgavimab injection even 3 months later (7235 vs. 1647 BAU/mL, p = 0.0007). Overall, breakthrough infections were rare (13/132, 10%) when compared to overall infection rates during this period (over 30% of the Austrian population), with mild disease course and rapid viral clearance (median 10 days). Sotrovimab may be an additional option for SARS-CoV-2 PrEP.

Keywords: SARS-CoV-2 PrEP; immunocompromised patients; pre-exposure prophylaxis; sotrovimab; tixagevimab/cilgavimab.

Figure 1

Flowchart showing the distribution of initial and follow-up PrEP among SOT and TIX/CIL. Antibody values resulting from follow-up PrEP were not analyzed due to the heterogeneity of mAb sequence and follow-up timing. The green border highlights included measurements; the red borders highlight excluded measurements. PrEP = Pre-exposure prophylaxis; SOT = sotrovimab; TIX/CIL = tixagevimab/cilgavimab; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Figure 2

Graphs displaying the measured antibody values after first PrEP (before administration of any further PrEP), separated by time point. (A) shows all values after first PrEP, with SOT and TIX/CIL respectively. Each line represents a patient. The table shows the number of measurements available at each time point. (B) shows the median values of A. Error bars show 95% confidence interval. Mann–Whitney U test was used to compare the values at T1 and T3. T0 +1 h contains antibody values measured 1 h after SOT infusion, which could not be obtained for TIX/CIL due to delayed release after intramuscular injection. Dashed lines symbolize the inaccurate representation of pharmacokinetics in this case. BAU = binding antibody units; mL = milliliter; PrEP = pre-exposure prophylaxis; SOT = sotrovimab; TIX/CIL = tixagevimab/cilgavimab; T0–T3 = time points of measurements, roughly equal to months since first PrEP.

Figure 3

Graph of the BIs that occurred. Each red line represents a patient with BI while all patients without BI are greyed out. The time point of BI is highlighted with a red cross. The dotted lines are projections of the last available values for patients with missing follow-up measurements. Three patients with BI are not represented in this graph due to missing antibody values. BI = breakthrough infection; PrEP = pre-exposure prophylaxis; BAU = binding antibody units; mL = milliliter; T0–T3 = time points of measurements, roughly equal to months since first PrEP.