Early treatment with sotrovimab monoclonal antibody in kidney transplant recipients with Omicron infection

Early data about coronavirus disease 2019 (COVID-19) related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) suggest that it may be less severe than prior variants of concern in the general population.1Maslo C. Friedland R. Toubkin M. et al.Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves.JAMA. 2022; 327: 583-584Crossref PubMed Scopus (84) Google Scholar, 2Ulloa A.C. Buchan S.A. Daneman N. Brown K.A. Estimates of SARS-CoV-2 Omicron variant severity in Ontario, Canada.JAMA. 2022; 327: 1286-1288Crossref PubMed Scopus (20) Google Scholar, 3Iuliano A.D. Brunkard J.M. Boehmer T.K. et al.Trends in disease severity and health care utilization during the early Omicron variant period compared with previous SARS-CoV-2 high transmission periods—United States, December 2020-January 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 146-152Crossref PubMed Scopus (55) Google Scholar However, our preliminary data (NC, personal communication, January 28, 2022) about Omicron infection in kidney transplant recipients (KTRs) suggest that the disease is associated with severe forms in this vulnerable population with low postvaccinal immune responses. Sotrovimab monoclonal antibody has been demonstrated to reduce disease progression in high-risk patients with mild-to-moderate COVID-19 before the Omicron era.4Gupta A. Gonzalez-Rojas Y. Juarez E. et al.Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab.N Engl J Med. 2021; 385: 1941-1950Crossref PubMed Scopus (204) Google Scholar Recent studies assessed that, in contrast with other monoclonal antibodies, it remained active against the Omicron spike.5Hoffmann M. Krüger N. Schulz S. et al.The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic.Cell. 2022; 185: 447-456.e11Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar We aimed to compare the clinical outcomes of the first 25 KTRs treated with sotrovimab for mild-to-moderate Omicron COVID-19 with KTRs who did not receive sotrovimab. Sotrovimab was available in our institution (Necker Hospital, Paris, France) from January 25, 2022. KTRs with a high risk for progression of COVID-19 (because of older age [≥55 years] or because they had at least 1 of the following risk factors: diabetes, obesity [body mass index >30, estimated glomerular filtration rate <30 ml/min], coronary artery disease, or chronic lung disease) who presented with mild-to-moderate Omicron COVID-19 after this date were treated with sotrovimab (a single 500-mg, 1-hour infusion). The control group consisted of the first 100 consecutive KTRs who experienced Omicron infection before January 25. We excluded patients who received pre-exposure prevention with tixagévimab/cilgavimab. A total of 25 patients (21 men [84%], median age of 54 years, interquartile range: 46–62 years) who developed an Omicron infection between January 14 and February 13, 2022, received sotrovimab (Table 1). Sixteen of 23 (69.6%) patients with available data had a COVID-19 serostatus predictive of a poor protection against Omicron (seronegative or weakly seropositive [<264 binding antibody units/ml] and/or treated with casirivimab/imdevimab). Antibody titers of seropositive patients are available in Supplementary Table S1). No infusion-related reaction was observed. Median time between symptom onset and sotrovimab infusion was 5 (interquartile range: 3–9) days. (Eight patients [32%] were treated after day 5 [up to day 13] of symptom onset.) Although sotrovimab-treated patients presented more risk factors associated with severe COVID-19 (significantly more men and more underlying comorbidities; Table 1), Omicron infection was less severe (less mortality and less severe disease [mortality and/or intensive care unit admission]) compared with controls (Figure 1). In the sotrovimab group, 4 (16.0%) patients were hospitalized, of whom, 1 patient required intensive care unit admission and no patients died. The patient admitted in intensive care unit received sotrovimab at day 11 after symptom onset. In contrast, 35 patients (35%) were hospitalized for Omicron disease in the control group. Among them, 17% required intensive care unit admission (9% needed mechanical ventilation) and 11% died.Table 1Baseline and COVID-19 characteristics of KTRs infected with Omicron variant who received or not sotrovimabVariablesSotrovimab-treated KTRs (N = 25)Nonsotrovimab-treated KTRs (N = 100)PAge, median (IQR)54 (46–62)53 (37.8–52)0.599Sex (males), n (%)21 (84.0)54 (54.0)0.006BMI, kg/m2, median (IQR)24 (22–25.6)25.5 (22.6–30)0.162BMI >30 kg/m2, n (%)2 (8.0)23 (24.5)0.101Hypertension, n (%)20 (80.0)81 (82.7)0.773Coronary artery disease, n (%)6 (24.0)13 (13.3)0.217Diabetes mellitus, n (%)8 (32.0)34 (34.7)1.000Chronic lung disease, n (%)5 (20.0)4 (4.1)0.017eGFR <30 ml/min per 1.73 m2,aDetermined with the Modification of Diet in Renal Disease equation. n (%)8 (32.0)7 (7.1)0.003KT >1, n (%)5 (20.0)21 (21)1.000Induction immunosuppressive therapy, n (%) Antithymocyte globulin7 (31.8)46 (46)0.246 Basiliximab14 (63.6)44 (44)0.105 Rituximab at induction4 (16)8 (8)0.256Maintenance immunosuppressive therapy Calcineurin inhibitors, n (%)20 (80.0)75 (75.0)0.794 Azathioprine, n (%)2 (8.0)6 (6.0)0.660 Mycophenolic acid, n (%)18 (72.0)84 (84.0)0.246 Dose, mg/d, median (IQR)1000 (1000–1500)1000 (1000–1500)0.407 mTOR-i (everolimus), n (%)1 (4.0)3 (3.0)1.000 Steroids, n (%)24 (96.0)96 (96.0)1.000 Dose, mg/d, median (IQR)8 (6–10)7.5 (5–10)0.179 Belatacept, n (%)3 (12.0)21 (21.0)0.402Anti-SARS-2 mRNA vaccination (Pfizer–BioNTech), n (%)23 (92.0)88 (92.6)1.000 1 injection1 (4.0)1 (1.1)0.377 2 injections1 (4.0)5 (5.3)1.000 3 injections16 (64)58 (61.1)0.822 4 injections3 (12.0)24 (25.3)0.188Positive serology at Omicron infection, n (%)7/23 (30.4)21/45 (46.7)0.298Anti-S titer, BAU/ml192 (30–744)260 (60–1010)0.349 Previous history of COVID-19, n (%)2 (8.0)13 (13)0.734Characteristics of Omicron infection Time between KT and Omicron infection, yr, median (IQR)7 (5–14)6 (2.8–11)0.140 Clinical symptoms at presentation, n (%)N = 23N = 86Cough16 (69.6)46 (51.1)0.236Asthenia10 (43.5)45 (50.0)0.489Fever14 (60.9)37 (41.1)0.160Rhinitis6 (26.1)36 (40.0)0.229Myalgia5 (21.7)31 (34.4)0.223Sore throat8 (34.8)30 (33.3)1.000Diarrhea5 (21.7)23 (25.6)0.791Headache9 (39.1)22 (24.4)0.206Dyspnea0 (0)15 (16.7)0.037Asymptomatic2 (8.7)7 (7.8)1.000 Time between symptom onset and sotrovimab injection, d, median (IQR)5 (3–9)–– Follow-up after infection, d, median (IQR)30 (27–34)20 (11–27)0.011BAU, binding antibody units; BMI, body mass index; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; IQR, interquartile range; KT, kidney transplantation; KTRs, kidney transplant recipients; mTOR, mammalian target of rapamycin; S, spike.Bold values of P < 0.05 were considered statistically significant.a Determined with the Modification of Diet in Renal Disease equation. Open table in a new tab BAU, binding antibody units; BMI, body mass index; COVID-19, coronavirus disease 2019; eGFR, estimated glomerular filtration rate; IQR, interquartile range; KT, kidney transplantation; KTRs, kidney transplant recipients; mTOR, mammalian target of rapamycin; S, spike. Bold values of P < 0.05 were considered statistically significant. Omicron infection appears to be severe in KTRs. Our study reports the first cohort of KTRs treated with sotrovimab for Omicron infection. Although these patients presented high risk for progression to severe disease, the severity of COVID-19 was lower than the historical control group, concordant with findings in the general population. Interestingly, the rate of patients with SARS-CoV-2–positive immune response was similar (and low) in both groups. Despite its retrospective character and the relatively short follow-up, our findings show that the sotrovimab-neutralizing anti-SARS-CoV-2 antibody can prevent severe COVID-19 in KTRs infected with the Omicron variant and can be safely proposed in outpatient KTRs. The data that support the findings of this study are available from the corresponding author at [email protected] . All the authors declared no competing interests. Download .docx (.02 MB) Help with docx files Supplementary File (Word)