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.

Efficacy and Safety of Tixagevimab/Cilgavimab to Prevent COVID-19 (Pre-Exposure Prophylaxis): A Systematic Review and Meta-Analysis

“…The full texts of the 76 remaining articles were reviewed, and 46 irrelevant articles were excluded (reasons: study with in vitro activity of TGM/CGM to prevent SARS-CoV-2 variants = 13, study with no relevant data = 13, review = 12, study with in silico activity of TGM/CGM to prevent SARS-CoV-2 variants = 4, study with no extractable data = 3, and editorial and commentary = 1). As a result, we identified 30 studies (total participants = 27,932) that met our inclusion criteria and were included in the systematic review and meta-analysis [ 6 , 9 , 10 , 11 , 12 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. The PRISMA chart for the studies included is displayed in Figure 2 .…”

“…Among these, two articles were in preprint versions [ 26 , 35 ]. Most of the studies were cohorts ( n = 23) [ 6 , 10 , 11 , 12 , 20 , 21 , 22 , 23 , 26 , 27 , 30 , 31 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], however, there were one case report [ 24 ] and five case series studies [ 25 , 28 , 29 , 32 , 34 ]. These studies were conducted in United States ( n = 14), France ( n = 11), Israel ( n = 2), Germany ( n = 1), and Austria ( n = 1).…”

“…Only one study was conducted within several countries ( n = 1) [ 9 ]. The majority of the studies were single center [ 6 , 11 , 12 , 23 , 24 , 25 , 26 , 28 , 29 , 31 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 41 , 42 , 44 ], and only ten studies were multicenter [ 9 , 10 , 20 , 21 , 22 , 27 , 30 , 35 , 40 , 43 ]. Studies randomly assigned participants into a TGM/CGM therapy versus a placebo [ 9 , 10 , 12 , 35 ], a combination of casirivimab/imdevimab (CRM/IDM) [ 11 , 21 , 37 ], or no treatment (no mAbs) [ 11 , 25 , 27 , 29 , 31 , 37 , 40 ].…”

“…Few studies utilized a pre–post design (baseline) [ 6 , 23 , 26 , 36 ] and only one study utilized the design of randomized double-blind controlled trial [ 9 ]. Many studies compared TGM/CGM groups to no comparator groups [ 20 , 22 , 24 , 28 , 30 , 32 , 33 , 34 , 36 , 38 , 39 , 41 , 42 , 43 , 44 ] or patient groups that were infected previously with SARS-CoV-2 and recovered [ 21 ]. Only twelve studies reported on the safety of TGM/CGM in patients at high risk for breakthrough and severe SARS-CoV-2 infection [ 9 , 10 , 11 , 25 , 26 , 28 , 34 , 39 , 41 , 42 , 43 , 44 ].…”

“…There was a slightly higher male percentage in patients who received TGM/CGM as PrEP against COVID-19 ( n = 5590/8903, 62.8%). Participants were immunocompromised ( n = 18,611) [ 22 , 25 , 27 , 29 , 30 , 32 , 35 , 39 , 40 , 44 ], high-risk patients for severe COVID-19 (obesity (BMI ≥ 30), hypertension, smoking, diabetes, asthma, chronic heart or kidney or liver diseases, or receipt of immunosuppressive therapy) ( n = 8621) [ 9 , 30 , 35 , 44 ], solid organ transplant recipients (kidney, liver, lung, and multiorgan) ( n = 3111) [ 6 , 10 , 11 , 12 , 20 , 21 , 26 , 28 , 30 , 38 , 42 , 44 ], hematologic malignancy patients ( n = 1320) [ 30 , 31 , 32 , 33 , 37 , 38 , 44 ], inborn error of immunity and immune-mediated inflammatory diseases patients ( n = 445) [ 30 , 38 , 43 ], B-cell malignancy patients ( n = 251) [ 41 ], autoimmune disease patients ( n = 229) [ 25 , 32 , 38 , 44 ], multiple sclerosis patients ( n = 45) [ 23 , 34 , 38 ...…”