Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis

Eva Stadler; Khai Li Chai; Timothy E Schlub; Deborah Cromer; Shanchita R Khan; Mark N Polizzotto; Stephen J Kent; Claire Beecher; Heath White; Tari Turner; Nicole Skoetz; Lise Estcourt; Zoe K McQuilten; Erica M Wood; David S Khoury; Miles P Davenport

doi:10.1016/S2666-5247(23)00194-5

Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis

Lancet Microbe. 2023 Nov;4(11):e883-e892. doi: 10.1016/S2666-5247(23)00194-5.

Authors

Affiliations

¹ Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
² Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Haematology, Monash Health, Clayton, VIC, Australia.
³ Kirby Institute, University of New South Wales, Sydney, NSW, Australia; Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
⁴ Clinical Hub for Interventional Research and John Curtin School of Medical Research, College of Health and Medicine, The Australian National University, Canberra, ACT, Australia; Canberra Regional Cancer Centre, The Canberra Hospital, Canberra, ACT, Australia.
⁵ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University, Melbourne, VIC, Australia; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁶ School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
⁷ Evidence-based Medicine, Department of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁸ Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁹ Kirby Institute, University of New South Wales, Sydney, NSW, Australia. Electronic address: dkhoury@kirby.unsw.edu.au.

PMID: 37924835
DOI: 10.1016/S2666-5247(23)00194-5

Abstract

Background: Randomised controlled trials of passive antibodies as treatment and prophylaxis for COVID-19 have reported variable efficacy. However, the determinants of efficacy have not been identified. We aimed to assess how the dose and timing of administration affect treatment outcome.

Methods: In this systematic review and meta-analysis, we extracted data from published studies of passive antibody treatment from Jan 1, 2019, to Jan 31, 2023, that were identified by searching multiple databases, including MEDLINE, PubMed, and ClinicalTrials.gov. We included only randomised controlled trials of passive antibody administration for the prevention or treatment of COVID-19. To compare administered antibody dose between different treatments, we used data on in-vitro neutralisation titres to normalise dose by antibody potency. We used mixed-effects regression and model fitting to analyse the relationship between timing, dose and efficacy.

Findings: We found 58 randomised controlled trials that investigated passive antibody therapies for the treatment or prevention of COVID-19. Earlier clinical stage at treatment initiation was highly predictive of the efficacy of both monoclonal antibodies (p<0·0001) and convalescent plasma therapy (p=0·030) in preventing progression to subsequent stages, with either prophylaxis or treatment in outpatients showing the greatest effects. For the treatment of outpatients with COVID-19, we found a significant association between the dose administered and efficacy in preventing hospitalisation (relative risk 0·77; p<0·0001). Using this relationship, we predicted that no approved monoclonal antibody was expected to provide more than 30% efficacy against some omicron (B.1.1.529) subvariants, such as BQ.1.1.

Interpretation: Early administration before hospitalisation and sufficient doses of passive antibody therapy are crucial to achieving high efficacy in preventing clinical progression. The relationship between dose and efficacy provides a framework for the rational assessment of future passive antibody prophylaxis and treatment strategies for COVID-19.

Funding: The Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council, the University of New South Wales, Monash University, Haematology Society of Australia and New Zealand, Leukaemia Foundation, and the Victorian Government.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal
Australia
COVID-19 Serotherapy
COVID-19* / therapy
Humans
SARS-CoV-2
Treatment Outcome

Substances

Antibodies, Monoclonal