Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron-Infected Immunocompromised Patients
Gliga et al.,
Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)..,
Clinical Infectious Diseases, doi:10.1093/cid/ciac802
Prospective analysis of 57 COVID-19 patients receiving sotrovimab, showing rapid creation of escape mutations within immunodeficient patients. Combined treatment with remdesivir reduced the creation of escape variants.
Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.1 [Liu, Sheward, VanBlargan] and a lack of efficacy for BA.2 [Zhou]. US EUA has been revoked.
Gliga et al., 3 Oct 2022, prospective, Germany, peer-reviewed, 21 authors, study period 20 January, 2022 - 25 February, 2022.
Contact:
nadine.luebke@med.uniduesseldorf.de.
Abstract: Clinical Infectious Diseases
MAJOR ARTICLE
Rapid Selection of Sotrovimab Escape Variants in
Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) Omicron-Infected Immunocompromised Patients
Smaranda Gliga,1,2,a Nadine Lübke,2,a, Alexander Killer,1,a Henning Gruell,3 Andreas Walker,2 Alexander T. Dilthey,4 Alexander Thielen,5 Carolin Lohr,1
Charlotte Flaßhove,1 Sarah Krieg,1 Joanna Ventura Pereira,1 Tobias Paul Seraphin,1 Alex Zaufel,1 Martin Däumer,5 Hans-Martin Orth,1 Torsten Feldt,1
Johannes G. Bode,1 Florian Klein,3,6 Jörg Timm,2 Tom Luedde,1,a and Björn-Erik Ole Jensen1,a
1
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 2Institute of
Virology, University Hospital Düsseldorf, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 3Institute of Virology, Faculty of Medicine and University Hospital Cologne,
University of Cologne, Cologne, Germany; 4Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 5Institute of
Immunology and Genetics, Kaiserslautern, Germany; and 6Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
Background. Monoclonal antibodies (mAbs) that target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are
predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral
shedding, resulting in an increased risk of viral escape.
Methods. In an observational, prospective cohort, 57 patients infected with Omicron variants who received sotrovimab alone or
in combination with remdesivir were followed. The study end points were a decrease in SARS-CoV-2 RNA <106 copies/mL in
nasopharyngeal swabs at day 21 and the emergence of escape mutations at days 7, 14, and 21 after sotrovimab administration.
All SARS-CoV-2 samples were analyzed using whole-genome sequencing. Individual variants within the quasispecies were
subsequently quantified and further characterized using a pseudovirus neutralization assay.
Results. The majority of patients (43 of 57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ
transplantation or hematologic malignancies. Infections by Omicron/BA.1 comprised 82.5%, while 17.5% were infected by Omicron/
BA.2. Twenty-one days after sotrovimab administration, 12 of 43 (27.9%) immunodeficient patients had prolonged viral shedding
compared with 1 of 14 (7.1%) immunocompetent patients (P = .011). Viral spike protein mutations, some specific for Omicron (e.g.,
P337S and/or E340D/V), emerged in 14 of 43 (32.6%) immunodeficient patients, substantially reducing sensitivity to sotrovimab in a
pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced emergence of escape variants.
Conclusions. Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape
mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need for
dedicated clinical trials in this patient population.
Keywords. immunodeficiency; sotrovimab; SARS-CoV-2; Omicron; escape.
During the severe acute respiratory syndrome coronavirus 2
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