Paul Ehrlich later produced a seminal article tying the curative antiserum to neutralizing antibodies 10. ![]() More than 125 years ago, the first major success in modern immunological intervention was developed: a therapeutic serum from animals actively immunized against diphtheria toxin 8, 9. Answers to these questions will allow the most efficacious use of these novel and potentially life-saving treatments, as we discuss herein. Furthermore, any protection offered would be temporary, and the duration of effective protection remains to be determined. However, mAbs are complicated to produce and may be limited in initial supply. The antiviral activity seen with neutralizing mAb treatment emphasizes the importance of early intervention to help counter the devastating impact the virus has had in such vulnerable populations and in other high-risk patients. While vaccines remain the best strategy to prevent COVID-19, mAbs could potentially benefit certain vulnerable populations before or after exposure to SARS-CoV-2, such as the unvaccinated or recently vaccinated high-risk patients. Indeed, preliminary non-peer-reviewed preprint data suggest that mAbs prevent COVID-19 in high-risk individuals potentially exposed to SARS-CoV-2 in nursing homes or within households 6, 7. Therefore, several questions need to be addressed about the potential clinical use of neutralizing SARS-CoV-2 mAbs: who should get them what is the best dose and frequency when in the course of the infection will they be most effective what is the duration of the protection they provide and what is their associated benefit-to-risk ratio? In addition, neutralizing mAbs may have a prophylactic role in individuals deemed to be at high risk of severe COVID-19. In the United States, three anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb therapies have been granted emergency use authorization (EUA) for treatment of non-hospitalized patients with mild-to-moderate COVID-19 - these are bamlanivimab as a monotherapy, and bamlanivimab together with etesevimab or casirivimab with imdevimab as a combination therapy 3, 4, 5. In this Review, we highlight the relative value that neutralizing mAbs can provide for patients and physicians, and go on to examine the role of these agents among the spectrum of potential treatments for COVID-19. These mAbs are termed ‘neutralizing’ and can ultimately be used as a type of passive immunotherapy (detailed later) to minimize virulence. High-throughput screening of these B cells permits the identification of antibodies with the necessary specificity and affinity to bind to a virus and block entry of the virus, therefore abrogating pathology associated with productive infection. Neutralizing mAbs are recombinant proteins that can be derived from the B cells of convalescent patients or humanized mice (Fig. ![]() Monoclonal antibodies (mAbs) that can bind to and ‘neutralize’ the virus in infected patients are a novel class of antiviral intervention 1, 2. In the midst of the current COVID-19 pandemic, a variety of prophylactic and therapeutic treatments are being developed or repurposed to combat COVID-19. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants. ![]() We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials.
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