Gliga, Smaranda, Luebke, Nadine, Killer, Alexander, Gruell, Henning, Walker, Andreas, Dilthey, Alexander T., Thielen, Alexander, Lohr, Carolin, Flasshove, Charlotte, Krieg, Sarah ORCID: 0000-0003-0012-0304, Pereira, Joanna Ventura, Seraphin, Tobias Paul, Zaufel, Alex, Daeumer, Martin, Orth, Hans-Martin, Feldt, Torsten, Bode, Johannes G., Klein, Florian ORCID: 0000-0003-1376-1792, Timm, Joerg, Luedde, Tom ORCID: 0000-0002-6288-8821 and Jensen, Bjoern-Erik Ole . Rapid Selection of Sotrovimab Escape Variants in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron-Infected Immunocompromised Patients. Clin. Infect. Dis.. CARY: OXFORD UNIV PRESS INC. ISSN 1537-6591

Full text not available from this repository.

Abstract

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 <10(6) 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. Immunodeficient patients had prolonged viral shedding of severe acute respiratory syndrome coronavirus 2 Omicron variants after treatment with sotrovimab. This was associated with rapid selection of escape mutations, which was confirmed in a pseudovirus neutralization assay but was significantly reduced by combination therapy with remdesivir.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gliga, SmarandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luebke, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Killer, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dilthey, Alexander T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thielen, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lohr, CarolinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flasshove, CharlotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krieg, SarahUNSPECIFIEDorcid.org/0000-0003-0012-0304UNSPECIFIED
Pereira, Joanna VenturaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seraphin, Tobias PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zaufel, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daeumer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orth, Hans-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Feldt, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bode, Johannes G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDorcid.org/0000-0003-1376-1792UNSPECIFIED
Timm, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luedde, TomUNSPECIFIEDorcid.org/0000-0002-6288-8821UNSPECIFIED
Jensen, Bjoern-Erik OleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-673105
DOI: 10.1093/cid/ciac802
Journal or Publication Title: Clin. Infect. Dis.
Publisher: OXFORD UNIV PRESS INC
Place of Publication: CARY
ISSN: 1537-6591
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Immunology; Infectious Diseases; MicrobiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67310

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item