Title: Monoclonal Antibody Therapy for SARS-CoV-2 Infection in Kidney Transplant Recipients: A Case Series From Belgium
Abstract: Kidney transplant recipients (KTRs) are particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and may remain at risk after complete vaccination because of poor response rate.1,2 Neutralizing monoclonal antibodies (Abs) have been shown to be safe and efficient in reducing viral load in immunocompetent outpatients with coronavirus disease 2019 (COVID-19).3 In immunocompromised patients, including solid organ transplant recipients, few reports have reported similar results.4,5 In this article, we report the efficacy and safety of monoclonal Ab therapy (intravenous casirivimab 1200 mg and imdevimab 1200 mg, Regeneron Pharmaceuticals, Terrytown, NY) in 12 KTRs infected by SARS-CoV-2 who were treated in our center between June and September 2021. The study received institutional review board approval. The mean age was 47 (range, 21–78) y and 6 patients (50%) were male (Table 1). The mean time from transplantation was 112 mo (range, 2–264). Eight patients (75%) were treated with an association of tacrolimus (Tac), mycophenolate (MPA), and steroids, and 4 patients (25%) were treated with dual therapy (Tac/MPA n = 2; Tac/steroids n = 1; Tac/azathioprine n = 1). Ten patients had received 2 doses of the mRNA BNT162b2 (Pfizer-BioNTech), with a mean time of 111 (range, 39–200) d before SARS-CoV-2 infection. Two of the vaccinated patients had a prior history of COVID-19. TABLE 1. - Characteristics of patients at SARS-CoV-2 infection Patients Age (y) Gender Male/Female Delay from KT (mo) IS at diagnosis Prior vaccine (Y/N) Last dose to infection delay (d) Anti-RBD titer before diagnosis (BAU/mL) Last titer to infection delay (d) Symptoms Viral load (×106 copies/mL) Genotype 1 64 Male 264 Tac-MPA-St Yes 57 0 13 F 10 Gamma 2 43 Female 60 Tac-MPA-St Yes 85 10.6 49 C 28 Delta 3 52 Male 2 Tac-MPA-St Yes 116 0 42 M – – 4 23 Male 55 Tac-MPA-St Yes 99 257.22 45 C-R 36 Delta 5 31 Female 22 Tac-MPA-St Yes 39 0 0 M 0.17 Delta 6 65 Female 133 Tac-MPA No – – 0 F-H 6 Delta 7 43 Male 196 Tac-MPA-St No – – 0 F-C 0.43 – 8 35 Female 190 Tac-AZA Yes 200 257.22 75 F-C-H – – 9 78 Female 262 Tac-MPA Yes 139 159.77 0 F-R 85 – 10 52 Female 69 Tac-St Yes 119 5.35 0 F-C-H 9 – 11 21 Male 28 Tac-MPA-St Yes 117 239.71 4 F 5.7 – 12 60 Male 61 Tac-MPA-St Yes 139 1.31 34 F-C-D 18.8 – AZA, azathioprine; BAU, binding antibody units; C, cough; D, diarrhea; F, fever; H, headache; IS, immunosuppressive drugs; KT, kidney transplantation; M, myalgia; MPA, mycophenolate; R, rhinorrhea; RBD, receptor-binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; St, steroids; Tac, tacrolimus. Out of the 7 patients who mounted a humoral response after vaccination, the mean anti–receptor-binding domain Ab titer (Elecsys anti–SARS-CoV-2, Roche Diagnostics GmbH, Mannheim, Germany; positive threshold ≥0.8 BAU/mL) was 133.03 (range, 1.31–257.22) BAU/mL, which was assessed a mean time of 22 (range, 0–75) d before infection. Patients presented with mild symptoms (fever n = 8; cough n = 6; headache n = 3; myalgia n = 3; rhinorrhea n = 2; diarrhea n = 1) and tested positive for SARS-CoV-2 using polymerase chain reaction on nasopharyngeal swab. The mean time between the beginning of symptoms and diagnosis was 3.75 (range, 2–7) d. The mean viral load at diagnosis was 3.62 × 106 (range, 171 × 103–85 × 106) copies/mL. Viral genotyping (available for 5 patients) revealed the Delta variant (n = 4) and the Gamma variant (n = 1) according to World Health Organization nomenclature. MPA was discontinued for 10 d in all patients. Nine patients were discharged the day of the diagnosis after receiving the Ab therapy. Three patients were hospitalized, and interestingly, the 2 unvaccinated KTRs required oxygen supplementation for 24 h. All were discharged the day after. One patient experienced a mild allergic reaction during Ab infusion that required a brief interruption of the perfusion. No other side effect was reported. The follow-up consisted of a repeated polymerase chain reaction on nasopharyngeal swab 7 d after treatment administration. The viral load was <1000 copies/mL in all patients. All KTRs reported a rapid resolution of symptoms and none necessitated a new hospitalization. Our results show that monoclonal Ab therapy is safe and associated with favorable outcomes in SARS-CoV-2–infected KTRs. Additional studies are required to assess the efficacy of this treatment in larger cohorts and in more severe forms of COVID-19 infection.