Breakthrough omicron COVID-19 infections in patients receiving the REGEN-Cov antibody combination

Abstract

Coronavirus disease 2019 (COVID-19) vaccines are efficient to prevent severe COVID-19 infections. Immunocompromised patients are at increased risk of both severe COVID-19 and poor immunologic response to anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Preexposure prophylaxis using anti-spike neutralizing monoclonal antibodies to prevent COVID-19 infection has been proposed as an alternative in patients with no immunologic response after 3 doses of COVID-19 vaccines.1Ducloux D. Courivaud C. REGEN-Cov antibody combination to prevent COVID-19 infection in kidney transplant recipient without detectable antibody response to optimal vaccine scheme.Kidney Int. 2022; 101: 645-646Google Scholar,2O’Brien M.P. Forleo-Neto E. Musser B.J. et al.Subcutaneous REGEN-COV antibody combination to prevent Covid-19.N Engl J Med. 2021; 385: 1184-1195Google Scholar We herein provide the first report, to our knowledge, of breakthrough COVID-19 infections in immunocompromised patients treated preventively with REGEN-Cov (Regeneron; casirivimab + imdevimab). Between September 24, 2021 and December 23, 2021, 80 patients who had received at least 3 doses of a COVID-19 vaccine and had a negative anti–SARS-CoV-2 spike protein antibody response received at least 1 injection of 600 mg of casirivimab and imdevimab for preexposure prophylaxis in our center (Figure 1). Causes of poor immunologic response to vaccination were kidney transplantation (n = 57 [71%]), treatment with rituximab (n = 9 [11%]), end-stage kidney disease (n = 7 [9%]), and other (n = 7 [9%]). All patients were asked to report COVID-19 infection. Among this cohort, we received 12 reports of COVID-19 infection between December 25, 2021, and January 18, 2022 (Figure 1). SARS-CoV-2 infection was diagnosed using an antigenic test in 1 case and by polymerase chain reaction test in the remaining 11 cases. The Omicron variant (the lack of the L452R mutation) was detected in 8 cases, whereas screening for Omicron was unavailable in the remaining 3 polymerase chain reaction–proven cases. Two patients were hospitalized because of severe symptoms but did not require a transfer to the intensive care unit. These breakthrough COVID-19 infections due to the Omicron variant are consistent with in vitro evidence of a complete escape of SARS-CoV-2 variant Omicron to casirivimab and imdevimab.3Planas D. Saunders N. Maes P. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2022; 602: 671-675Google Scholar,4Wilhelm A. Widera M. Grikscheit K. et al.Reduced neutralization of SARS-CoV-2 Omicron variant by vaccine sera and monoclonal antibodies. medRxiv.https://doi.org/10.1101/2021.12.07.21267432Google Scholar REGEN-Cov antibody combination to prevent COVID-19 infection in kidney transplant recipient without detectable antibody response to optimal vaccine schemeKidney InternationalVol. 101Issue 3PreviewMany kidney transplant recipients (KTRs) do not respond to an anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Indeed, concordant data indicate that about 30% of KTRs do not develop antibodies after 3 doses of mRNA vaccines.1,2 However, KTRs are at a high risk of severe forms of coronavirus disease 2019 (COVID-19) infection. Mortality rates are reported to reach 15% to 20%, and the need for hospitalization in an intensive unit care is even more likely.3 Full-Text PDF