{"title":"Single monoclonal antibodies should not be used for COVID-19 therapy: a call for antiviral stewardship.","authors":"Arturo Casadevall, Daniele Focosi, Liise-Anne Pirofski, Shmuel Shoham","doi":"10.1093/cid/ciae408","DOIUrl":null,"url":null,"abstract":"<p><p>The COVID-19 pandemic saw the largest deployment of monoclonal antibodies (mAbs) for an infectious disease in history. mAbs to SARS-CoV-2 spike protein proved safe and were initially effective for COVID-19 therapy, but each was defeated by continued SARS-CoV-2 evolution, leading to their withdrawal. This was a setback for people with impaired immunity who cannot mount an effective antibody response to SARS-CoV-2 and often cannot clear the virus. New mAbs have now been developed for pre-exposure prophylaxis (PreEP) in immunosuppressed people. Here we argue that while mAb use for PreEP is justified, single mAbs should not be used for COVID-19 therapy. In contrast to PreEP where the viral inoculum is small, immunosuppressed people with COVID-19 have large viral burden that can harbor mAb-escape variants that single-agent mAb treatments can rapidly select for resistance. Selection of mAb-escape variants has potential risks for patients, society and the feasibility of mAb therapy itself.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/cid/ciae408","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The COVID-19 pandemic saw the largest deployment of monoclonal antibodies (mAbs) for an infectious disease in history. mAbs to SARS-CoV-2 spike protein proved safe and were initially effective for COVID-19 therapy, but each was defeated by continued SARS-CoV-2 evolution, leading to their withdrawal. This was a setback for people with impaired immunity who cannot mount an effective antibody response to SARS-CoV-2 and often cannot clear the virus. New mAbs have now been developed for pre-exposure prophylaxis (PreEP) in immunosuppressed people. Here we argue that while mAb use for PreEP is justified, single mAbs should not be used for COVID-19 therapy. In contrast to PreEP where the viral inoculum is small, immunosuppressed people with COVID-19 have large viral burden that can harbor mAb-escape variants that single-agent mAb treatments can rapidly select for resistance. Selection of mAb-escape variants has potential risks for patients, society and the feasibility of mAb therapy itself.
期刊介绍:
Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.