Emergence of E484K Mutation Following Bamlanivimab Monotherapy among High-Risk Patients Infected with the Alpha Variant of SARS-CoV-2

被引:39
作者
Peiffer-Smadja, Nathan [1 ,2 ,3 ]
Bridier-Nahmias, Antoine [1 ]
Ferre, Valentine Marie [1 ,4 ]
Charpentier, Charlotte [1 ,4 ]
Gare, Mathilde [2 ]
Rioux, Christophe [2 ]
Allemand, Aude [2 ]
Lavallee, Philippa [5 ,6 ]
Ghosn, Jade [1 ,2 ]
Kramer, Laura [7 ]
Descamps, Diane [1 ,4 ]
Yazdanpanah, Yazdan [1 ,2 ]
Visseaux, Benoit [1 ,4 ]
机构
[1] Univ Paris, IAME, INSERM, UMR1137, F-75018 Paris, France
[2] Hop Bichat Claude Bernard, AP HP, Serv Malad Infect & Trop, F-75018 Paris, France
[3] Imperial Coll London, Natl Inst Hlth Res, Hlth Protect Res Unit Healthcare Associated Infec, London SW7 2AZ, England
[4] Hop Bichat Claude Bernard, AP HP, Serv Virol, F-75018 Paris, France
[5] Hop Bichat Claude Bernard, AP HP, Dept Neurol, F-75018 Paris, France
[6] Hop Bichat Claude Bernard, AP HP, Stroke Ctr, F-75018 Paris, France
[7] Hop Bichat Claude Bernard, AP HP, Pharm Dept, F-75018 Paris, France
来源
VIRUSES-BASEL | 2021年 / 13卷 / 08期
关键词
monoclonal antibodies; SARS-CoV-2; COVID-19; variants; resistance; ESCAPE;
D O I
10.3390/v13081642
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
An Emergency Use Authorization was issued in the United States and in Europe for a monoclonal antibody monotherapy to prevent severe COVID-19 in high-risk patients. This study aimed to assess the risk of emergence of mutations following treatment with a single monoclonal antibody. Bamlanivimab was administered at a single dose of 700 mg in a one-hour IV injection in a referral center for the management of COVID-19 in France. Patients were closely monitored clinically and virologically with nasopharyngeal RT-PCR and viral whole genome sequencing. Six patients were treated for a nosocomial SARS-CoV-2 infection, all males, with a median age of 65 years and multiple comorbidities. All patients were infected with a B.1.1.7 variant, which was the most frequent variant in France at the time, and no patients had E484 mutations at baseline. Bamlanivimab was infused in the six patients within 4 days of the COVID-19 diagnosis. Four patients had a favorable outcome, one died of complications unrelated to COVID-19 or bamlanivimab, and one kidney transplant patient treated with belatacept died from severe COVID-19 more than 40 days after bamlanivimab administration. Virologically, four patients cleared nasopharyngeal viral shedding within one month after infusion, while two presented prolonged viral excretion for more than 40 days. The emergence of E484K mutants was observed in five out of six patients, and the last patient presented a Q496R mutation potentially associated with resistance. CONCLUSIONS: These results show a high risk of emergence of resistance mutants in COVID-19 patients treated with monoclonal antibody monotherapy.
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页数:8
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