All Studies Meta Analysis

Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)

Horby et al., medRxiv, doi:10.1101/2025.01.24.25321081

Jan 2025

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Sotrovimab for COVID-19

40th treatment shown to reduce risk in August 2022, now with p = 0.0016 from 27 studies, recognized in 41 countries. Efficacy is variant dependent.

Lower risk for mortality, ICU, and hospitalization.

No treatment is 100% effective. Protocols combine treatments.

5,400+ studies for 118 treatments. c19early.org

RCT 1,723 hospitalized COVID-19 patients showing lower 28-day mortality with sotrovimab in patients with high serum nucleocapsid antigen levels, but no significant benefit in the overall population. Sotrovimab reduced mortality from 29% to 23% in high-antigen patients, however there was no significant difference in the overall population (21% vs. 22%; rate ratio 0.95; 95% CI 0.77-1.16; p=0.60). The trial used a higher dose of sotrovimab (1g) due to reduced neutralization activity against Omicron BA.1, and no new safety concerns were identified.

Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.11-3, BA.4, BA.54, XBB.1.9.3, XBB.1.5.24, XBB.2.9, CH.1.15, and no efficacy for BA.26, XBB, XBB.1.5, ХВВ.1.9.17, XBB.1.16, BQ.1.1.45, and CL.15. US EUA has been revoked.

Standard of Care (SOC) for COVID-19 in the study country, the United Kingdom, is very poor with very low average efficacy for approved treatments8. The United Kingdom focused on expensive high-profit treatments, approving only one low-cost treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of treatment—especially early—due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments. This may explain in part the very high mortality seen in this study. Results may differ in countries with improved SOC.

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risk of death, 5.0% lower, HR 0.95, p = 0.64, treatment 177 of 828 (21.4%), control 201 of 895 (22.5%), NNT 92, all patients, Cox proportional hazards.

risk of death, 25.0% lower, HR 0.75, p = 0.047, treatment 82 of 355 (23.1%), control 106 of 365 (29.0%), NNT 17, high antigen patients, Cox proportional hazards.

risk of no hospital discharge, 4.2% higher, RR 1.04, p = 0.51, treatment 828, control 895, adjusted per study, inverted to make RR<1 favor treatment, all patients.

risk of death/ICU, 2.0% lower, RR 0.98, p = 0.82, treatment 184 of 799 (23.0%), control 201 of 863 (23.3%), NNT 382, adjusted per study, all patients.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Liu et al., Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2, bioRxiv, doi:10.1101/2021.12.14.472719.biorxiv.org, doi.org.

2. Sheward et al., Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron), bioRxiv, doi:10.1101/2021.12.19.473354.biorxiv.org, doi.org.

3. VanBlargan et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies, bioRxiv, doi:10.1101/2021.12.15.472828.biorxiv.org, doi.org.

4. Haars et al., Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023, Microorganisms, doi:10.3390/microorganisms11102417.mdpi.com, doi.org.

5. Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.mdpi.com, doi.org.

6. Zhou et al., SARS-CoV-2 Omicron BA.2 Variant Evades Neutralization by Therapeutic Monoclonal Antibodies, bioRxiv, doi:10.1101/2022.02.15.480166.biorxiv.org, doi.org.

7. Uraki et al., Antiviral efficacy against and replicative fitness of an XBB.1.9.1 clinical isolate, iScience, doi:10.1016/j.isci.2023.108147.sciencedirect.com, doi.org.

8. c19early.org, c19early.org/soc/united-kingdom.html.c19early.org/soc/united-kingdom.html.

Horby et al., 27 Jan 2025, Randomized Controlled Trial, United Kingdom, peer-reviewed, 32 authors, study period 4 January, 2022 - 19 March, 2024.

This Paper Sotrovimab All

Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)

Prof Peter W Horby, Jonathan R Emberson, Leon Peto, Natalie Staplin, Mark Campbell, Guilherme Pessoa-Amorim, Richard Stewart, Dipansu Ghosh, Graham Cooke, Natalie Blencowe, Jeronimo Moreno-Cuesta, Purav Desai, Paul Hine, Jonathan Underwood, Nicholas Easom, Jaydip Majumdar, Sanjay Bhagani, J Kenneth Baillie, Maya H Buch, Saul N Faust, Thomas Jaki, Katie Jeffery, Edmund Juszczak, Marian Knight, Wei Shen Lim, Alan Montgomery, Aparna Mukherjee, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J Landray

doi:10.1101/2025.01.24.25321081

Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY)

Contributors This manuscript was initially drafted by LP, RH, PWH and MJL, further developed by the Writing Committee, and approved by all members of the trial steering committee. NS, JRE, PWH, MJL, RH and LP had access to the study data. NS and JRE accessed and verified the data. JRE did the statistical analysis. PWH and MJL vouch for the data and analyses, and for the fidelity of this report to the study protocol and data analysis plan, and had final responsibility for the decision to submit for publication. PWH, NS, JRE, JKB, MB, SNF, TJ, EJ, KJ, MK, WSL, AMo, AMuk, AMum, KR, GT, MM, RH, and MJL designed the trial and study protocol. MM, MC, G P-A, LP, RS, DG, GC, FH, JM-C, PD, PH, JU, NE, JM, SB, the Data Linkage team at the RECOVERY Coordinating Centre, and the Health Records and Local Clinical Centre staff listed in the appendix collected the data. All authors contributed to data interpretation and critical review and revision of the manuscript. Declaration of interests The authors have no conflict of interest or financial relationships relevant to the submitted work to disclose. No form of payment was given to anyone to produce the manuscript.

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Late treatment
is less effective

Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.

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