Patient 2 developed fever (about day time 5) and respiratory degradation (from day time 8) and died about day 17. Viral isolates from individual 1 and individual 2 belonged to clades 20A.EU2 and 20I/501Y.V1, respectively. COVID-19 onset and resulted in transient medical response in both individuals (appendix p 1). Patient 1 experienced two recurrences of fever (from day time 4 until day time 6 and from day time 15 until day time 20 after RWJ 50271 bamlanivimab treatment) and required oxygen supplementation during each show. Convalescent plasma was infused into patient 1 from day time 17 to day time 20, leading to medical improvement and decreased inflammatory syndrome. Patient 2 developed fever (on day time 5) and respiratory degradation (from day time 8) and died on day time 17. Viral isolates from patient 1 and patient 2 belonged to clades 20A.EU2 and 20I/501Y.V1, respectively. At the time of bamlanivimab infusion (day time 0), only one non-synonymous intra-host solitary nucleotide variant (ihSNV) was recognized in the Spike in patient 1 (Thr286Ala; rate of recurrence 3%), therefore no variant was recognized at position 484 in the Spike (Glu484) in either individual (appendix p 1). The Glu484Gln and Glu484Lys (individual 1 and individual 2) and Glu484Ala mutations (individual 1), which are known to be involved in neutralising antibody escape and resistance to bamlanivimab,5 appeared for both individuals within 7 days. Glu484Lys and Glu484Gln became predominant in patient 1 (90% by day time 19) and patient 2 (55% by day time 5), respectively. In individual 1, viral loads of SARS-CoV-2 were negatively associated with the proportion of wild-type Glu484. Even though viral load declined in patient 2 at day time 5, plasma was positive (43 log copies/mL) at day time 14, suggesting failure of treatment. Additional ihSNVs in the Spike were recognized during follow-up (Gln493Arg in patient 1 and Ser494Pro in both individuals; appendix p 2). These mutations were also selected for in vitro by bamlanivimab.5 Immunocompromised patients are prone to developing high intra-host diversity.3, 4, 5 Bamlanivimab rapidly selected Spike mutations at position 484 escape variants in two immunocompromised individuals. Such variants RWJ 50271 were not observed within immunocompromised individuals admitted to RWJ 50271 hospital but not treated with bamlanivimab at our hospital in 2021 (n=69, including 23 individuals with multiple samples). Although Mouse monoclonal to GFAP the US Food and Drug Administration revoked emergency use authorisation for bamlanivimab only, combination treatment with monoclonal antibodies might also select escape variants in immunocompromised individuals. This statement emphasises the importance of longitudinal SARS-CoV-2 sequencing with this populace. We declare no competing interests. BL is usually a member of the French Scientific Committee for SARS-CoV-2. We thank laboratory technicians and Quentin Semanas for their active participation and help with this study. This study was done as part of the global surveillance of influenza viruses by WHO and by the Centre National de Rfrence des Virus des Infections Respiratoires, supported by Sant Publique RWJ 50271 France in France. Patients were included in a temporary authorisation for use cohort for bamlanivimab infusion with unique authorisation (AU-041) for data collection and data sharing and including patient informed consent. Investigations were done in accordance with the General Data Protection Regulation (Regulation [EU] 2016/679 and Directive 95/46/EC) and French data protection law (Law 78C17 on Jan 6, 1978, and Dcret 2019C536 on May 29, 2019). Supplementary Material Supplementary appendix:Click here to view.(310K, pdf).
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