Breakthrough COVID-19 cases despite prophylaxis with 150 mg of tixagevimab and 150 mg of cilgavimab in kidney transplant recipients

Abstract

The cilgavimab−tixagevimab combination retains a partial in vitro neutralizing activity against the current SARS‐CoV‐2 variants of concern (omicron BA.1, BA.1.1, and BA.2). Here, we examined whether preexposure prophylaxis with cilgavimab−tixagevimab can effectively protect kidney transplant recipients (KTRs) against the omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of 150 mg tixagevimab and 150 mg cilgavimab, 39 (9.4%) developed COVID‐19. With the exception of one case, all patients were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients (7.7%), respectively. Two KTRs died of COVID‐19‐related acute respiratory distress syndrome. SARS‐CoV‐2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n = 1). Viral neutralizing activity of the serum against the BA.1 variant was negative in the 12 tested patients, suggesting that this prophylactic strategy does not provide sufficient protection against this variant of concern. In summary, preexposure prophylaxis with cilgavimab−tixagevimab at the dose of 150 mg of each antibody does not adequately protect KTRs against omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.

Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients

“…It included studies from the United States, France, Israel, Belgium, Spain and the United Kingdom. This review included ten retrospective cohort studies 12,[16][17][18][19][20][22][23][24][25] (including two preprints 16,20 ), six prospective, observational cohort studies [26][27][28][29][30][31] (also including one preprint…”

Real World Effectiveness of Tixagevimab/cilgavimab (Evusheld) in the Omicron Era

“…The authorization of T/C coincided with the emergence of the Omicron variant, which resulted in previously effective monoclonal antibodies losing effectiveness. 4 5 6 7 There is limited data available on the real-world effectiveness of T/C, especially in the Omicron era. T/C requires significant resources for administration due to its EUA status and associated institutional requirements for administering it.…”

A rapid decline in the anti–receptor-binding domain of the SARS-CoV-2 spike protein IgG titer in kidney transplant recipients after tixagevimab–cilgavimab administration

“…The PROVENT study demonstrated a persistent neutralizing activity against pre-omicron variants for 6 months after tixagevimab-cilgavimab administration despite a progressive decrease in drug concentration. 4 As the neutralizing activity is already reduced against the omicron variant in vitro and in vivo one month after the injection [5][6][7] , the significant decrease in anti-RBD titers indicate a potential rapid loss of efficacy and an increased risk of severe COVID-19 in transplant recipients. Despite the fact that all of the sera tested within 4−5 months after a 150 mg dose of tixagevimab and cilgavimab each exhibited neutralizing activity against BA.2,it should be kept in mind that the currently predominant variant (BA.5) is characterized by a higher resistance against tixagevimab-cilgavimab.…”