REGEN-Cov antibody combination to prevent COVID-19 infection in kidney transplant recipient without detectable antibody response to optimal vaccine scheme

Abstract

Many 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.1Ducloux D. Colladant M. Chabannes M. et al.Factors associated with humoral response after BNT162b2 mRNA COVID-19 vaccination in kidney transplant patients.Clin Kidney J. 2021; 14: 2270-2272Google Scholar,2Danthu C. Hantz S. Dahlem A. et al.Humoral response after SARS-CoV-2 mRNA vaccination in a cohort of hemodialysis patients and kidney transplant recipients.J Am Soc Nephrol. 2021; 32: 2153-2158Google Scholar 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.3Caillard S. Chavarot N. Francois H. et al.French SOT COVID RegistryIs COVID-19 infection more severe in kidney transplant recipients?.Am J Transplant. 2021; 21: 1295-1303Google Scholar In this setting, consideration for an alternative prevention strategy of COVID-19 infection is particularly required. Recently, the REGEN-Cov antibody combination (casirivimab + imdevimab; Regeneron Pharmaceuticals) has been proven to be efficient to prevent infection in persons at risk for infection because of household exposure to a person with SARS-CoV-2 infection.4O'Brien M.P. Forleo-Neto E. Musser B.J. et al.Covid-19 Phase 3 Prevention Trial Team. Subcutaneous REGEN-COV antibody combination to prevent Covid-19.N Engl J Med. 2021; 385: 1184-1195Google Scholar Nevertheless, no data are available for preexposition prevention in patients at risk. The French government recently authorized the use of REGEN-Cov to prevent COVID-19 infection in immunocompromised patients without any antibody response after 3 doses of anti–SARS-CoV-2 vaccine (https://www.has-sante.fr/jcms/p_3281999/fr/covid-19-autorisation-d-acces-precoce-accordee-a-un-traitement-prophylactique). We report the use of REGEN-Cov in preexposition prevention in KTRs. Among 402 KTRs having received 3 doses of vaccines and for whom serology was available, 119 (29.6%) had no antibody response (anti-S titer < 50 arbitrary units [AU]; SARS-CoV-2 immunoassay; Abbott; designed to detect IgG antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2). Preexposition prevention was proposed to all of them. During the study period, the delta variant accounted for >99% of COVID-19 cases. REGEN-Cov is effective against the delta variant.5Copin R. Baum A. Wloga E. et al.The monoclonal antibody combination REGEN-COV protects against SARS-CoV-2 mutational escape in preclinical and human studies.Cell. 2021; 184: 3949-3961Google Scholar The first dose of REGEN-Cov (1200 mg) was administered i.v. The subsequent doses (600 mg) were administered s.c. every 4 weeks. Nasopharyngeal swabs were obtained for patients to test for SARS-CoV-2 by quantitative reverse transcription polymerase chain reaction before each administration of REGEN-Cov. Anti-S antibodies were also measured before each treatment. Ninety-one patients (76%) accepted, whereas 28 refused. Among the 91 patients, only 88 received a first dose of REGEN-Cov. One experienced COVID-19 infection 3 days before the scheduled perfusion of REGEN-Cov, and 2 declined treatment after initial acceptance. Characteristics of the patients are depicted in Table 1.Table 1Characteristics of study patientsCharacteristicsParticipants (n = 88)Nonparticipants (n = 31)P valueAge, yr62 [55–70]61 [51–70]0.973Sex, % male63590.664Transplant vintage, mo29 [14–91]158 [60–194]0.145eGFR, ml/min per 1.73 m248 [30–68]47 [31–79]0.352CNI use, %81740.629MPA use, %81840.695mTORi use, %8100.767Belatacept use, %10100.928CNI, cancineurin inhibitors; eGFR, estimated glomerular filtration rate; MPA, mycophenolic acid; mTORi, mammalian target of rapamycin.Data are presented as median [interquartile range], 25th–75th interquartiles. Open table in a new tab CNI, cancineurin inhibitors; eGFR, estimated glomerular filtration rate; MPA, mycophenolic acid; mTORi, mammalian target of rapamycin. Data are presented as median [interquartile range], 25th–75th interquartiles. All of the 88 patients received at least 2 maintenance injections after the initial perfusion. No patient reported having been in contact with a COVID-19–positive person. No adverse effect was observed in any patient. No acute rejection occurred during the study period. Immunosuppressive treatment was not modified. During treatment, anti-S antibody titers were >40,000 AU in all patients. During the observed period, no patient of the prophylaxis group developed COVID-19 infection. By contrast, in those without prevention, 5 (16%; P < 0.001) experienced COVID-19 infection, and 2 of them required hospitalization in intensive care unit. One died 3 weeks after admission. REGEN-Cov is safe in preexposition prevention in KTRs without detectable vaccine response. High antibody titers are achieved in all patients. Preliminary data suggest efficient prevention of COVID-19 infection in this high-risk population. Breakthrough omicron COVID-19 infections in patients receiving the REGEN-Cov antibody combinationKidney InternationalVol. 101Issue 4PreviewCoronavirus 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. Full-Text PDF