Sotrovimab in Hospitalized Patients with SARS-CoV-2 Omicron Variant Infection: a Propensity Score-Matched Retrospective Cohort Study
Marcel S Woo, Thomas Theo Brehm, Marlene Fischer, Andreas Heyer, Dominic Wichmann, Sabine Jordan, Dominik Nörz, Marc Lütgehetmann, Marylyn M Addo, Ansgar W Lohse, Stefan Schmiedel, Stefan Kluge, Julian Schulze Zur Wiesch
Microbiology Spectrum, doi:10.1128/spectrum.04103-22
In vitro data suggest the monoclonal antibody sotrovimab may have lost inhibitory capability against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. We aimed to provide real-life data on clinical outcomes in hospitalized patients. We retrospectively analyzed patients who were treated at the University Medical Center Hamburg-Eppendorf, Germany, between December 2021 and June 2022. Out of all 1,254 patients, 185 were treated with sotrovimab: 147 patients received sotrovimab monotherapy, and 38 received combination treatment with sotrovimab and remdesivir. We compared in-hospital mortality for the different treatment regimens for patients treated on regular wards and the intensive care unit separately and performed propensity score matching by age, sex, comorbidities, immunosuppression, and additional dexamethasone treatment to select patients who did not receive antiviral treatment for comparison. No difference in in-hospital mortality was observed between any of the treatment groups and the respective control groups. These findings underline that sotrovimab adds no clinical benefit for hospitalized patients with SARS-CoV-2 Omicron variant infections. IMPORTANCE This study shows that among hospitalized patients with SARS-CoV-2 Omicron variant infection at risk of disease progression, treatment with sotrovimab alone or in combination with remdesivir did not decrease in-hospital mortality. These real-world clinical findings in combination with previous in vitro data about lacking neutralizing activity of sotrovimab against SARS-CoV-2 Omicron variant do not support sotrovimab as a treatment option in these patients.
References
Brehm, Heyer, Roedl, Jarczak, Nierhaus et al., Patient characteristics and clinical course of COVID-19 patients treated at a German tertiary center during the first and second waves in the year 2020, J Clin Med,
doi:10.3390/jcm10112274
Brehm, Pfefferle, Possel, Karolyi, Zoufaly et al., Clinical efficacy and in vitro neutralization capacity of monoclonal antibodies for severe acute respiratory syndrome coronavirus 2 delta and omicron variants, J Med Virol,
doi:10.1002/jmv.27916
Brehm, Van Der Meirschen, Hennigs, Roedl, Jarczak et al., Comparison of clinical characteristics and disease outcome of COVID-19 and seasonal influenza, Sci Rep,
doi:10.1038/s41598-021-85081-0
Cao, Wang, Jian, Song, Yisimayi et al., Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies, Nature,
doi:10.1038/s41586-021-04385-3
Dejnirattisai, Huo, Zhou, Zahradník, Supasa et al., SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses, Cell,
doi:10.1016/j.cell.2021.12.046
Gupta, Gonzalez-Rojas, Juarez, Casal, Moya et al., Early treatment for COVID-19 with SARS-CoV-2 neutralizing antibody sotrovimab, N Engl J Med,
doi:10.1056/NEJMoa2107934
Gupta, Gonzalez-Rojas, Juarez, Casal, Moya et al., Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial, JAMA,
doi:10.1001/jama.2022.2832
Nörz, Grunwald, Olearo, Fischer, Aepfelbacher et al., Evaluation of a fully automated high-throughput SARS-CoV-2 multiplex qPCR assay with built-in screening functionality for del-HV69/70-and N501Y variants such as B.1.1.7, J Clin Virol,
doi:10.1016/j.jcv.2021.104894
Nörz, Grunwald, Tang, Olearo, Günther et al., Rapid automated screening for SARS-CoV-2 B.1.617 lineage variants (Delta/ Kappa) through a versatile toolset of qPCR-based SNP detection, Diagnostics,
doi:10.3390/diagnostics11101818
Nörz, Grunwald, Tang, Weinschenk, Günther et al., Clinical evaluation of a fully-automated high-throughput multiplex screening-assay to detect and differentiate the SARS-CoV-2 B.1.1, Omicron),
doi:10.3390/v14030608
Piccicacco, Zeitler, Ing, Montero, Faughn et al., Real-world effectiveness of early remdesivir and sotrovimab in the highest-risk COVID-19 outpatients during the Omicron surge, J Antimicrob Chemother,
doi:10.1093/jac/dkac256
Takashita, Yamayoshi, Simon, Van Bakel, Sordillo et al., Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants, N Engl J Med,
doi:10.1056/NEJMc2207519
Vangeel, Chiu, Jonghe, Maes, Slechten et al., Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern, Antiviral Res,
doi:10.1016/j.antiviral.2022.105252
Who, WHO coronavirus (COVID-19) dashboard
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