Emergence of E484K Mutation Following Bamlanivimab Monotherapy among High-Risk Patients Infected with the Alpha Variant of SARS-CoV-2.
Viruses
; 13(8)2021 08 19.
Article
in English
| MEDLINE | ID: covidwho-1367917
ABSTRACT
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Antibodies, Monoclonal, Humanized
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Long Covid
/
Vaccines
/
Variants
Limits:
Adult
/
Aged
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
V13081642
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