Breakthrough Covid-19 cases despite tixagevimab and cilgavimab (Evusheld™) prophylaxis in kidney transplant recipients

While the combination of casirivimab-imdevimab (Ronapreve™ Roche Regeneron) has been shown to confer satisfactory protection against the delta variant kidney transplant recipients (KTRs) with COVID-19, it has limited neutralizing activity against the current variants of concern (Omicron BA.1, BA.1.1 and BA.2). In contrast, cilgavimab-tixagevimab combination (Evusheld™, Astra Zeneca) retains a partial neutralizing activity against omicron in vitro. We examined whether preexposure prophylaxis with Evusheld™ can effectively protect kidney transplant recipients (KTRs) against the Omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of Evusheld™ (150 mg tixagevimab and 150 mg cilgavimab), 39 (9.4%) developed COVID-19. With the exception of one patient, all KTRs were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients, 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 BA.1 variant was negative in the 12 tested patients, suggesting that this prophylaxis strategy provides insufficient protection against this variant of concern. Preexposure prophylaxis with Evusheld™ 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. ### Competing Interest Statement Sophie Caillard and Olivier Thaunat received consultant fees from Astra Zeneca. No other disclosures were reported. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All procedures complied with the Helsinki Declaration and were approved by the Institutional Review Board (comité d'éthique, Université de Strasbourg, Strasbourg, France, reference number: CE-2021-9). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors