Monoclonal Antibodies for Prevention and Treatment of COVID-19 | Infectious Diseases | JAMA | JAMA Network
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June 15, 2020

Monoclonal Antibodies for Prevention and Treatment of COVID-19

Author Affiliations
  • 1Vaccine Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
  • 2Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill
JAMA. 2020;324(2):131-132. doi:10.1001/jama.2020.10245

The coronavirus disease 2019 (COVID-19) pandemic has created a worldwide crisis and inspired an urgent search for prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Attention has focused on the development of vaccines, new antiviral agents, and convalescent plasma infusions. Monoclonal antibodies have received less attention even though neutralizing antibodies are a key component of protective immunity for most viral diseases. Neutralizing monoclonal antibodies to SARS-CoV-2 have the potential for both therapeutic and prophylactic applications, and can help to guide vaccine design and development.1

Since the identification of SARS-CoV-2 as the causative agent of COVID-19, numerous research groups have isolated monoclonal antibodies (most often from the B cells of patients who have recently recovered from SARS-CoV-2, and in some cases from individuals who were infected with the severe acute respiratory syndrome coronavirus [SARS-CoV] in 2003). It is also possible to generate effective monoclonal antibodies by immunization of humanized mice. Modern methods allow the rapid identification of pathogen-specific B cells and recovery of immunoglobulin heavy chain and light chain genes that can be expressed to produce monoclonal antibodies, usually in the form of IgG.

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    3 Comments for this article
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    Plasma vs Potentially Less Toxic IV IgG or Monoclonals
    Neil Blumberg, MD | University of Rochester
    The safety data on plasma is, I believe, not complete, because only acute reactions have been considered (a few hours). There are extensive observational data and in vitro data suggesting human allogeneic plasma may be immunomodulatory, interfering with NK and T cell function, and associated with serious adverse events that occur days after infusion. These include nosocomial infection, inflammation, organ injury and thrombosis. Such adverse events are even more clearly associated with the common practice of infusing non-ABO identical plasma, which generates immune complexes of soluble ABO antigen and antibody in vivo. ABO non-identical plasma transfusions have associations with bleeding, ARDS, organ injury and sepsis.

    Currently there are no data implicating IVIgG preparations with these adverse effects (excepting hemolysis), and most monoclonal therapeutics do not seem to have such unfavorable benefit:risk ratios. ABO matching is still a problem with IV IgG, which contains anti-A and anti-B. Newer preparations in development have the potential to reduce the risk of hemolysis and immune complex formation by removing much of the anti-A and anti-B. Monoclonals do not usually cross react with A and B antigens on red cells (and all the rest of the body's cells) and probably carry much less risk of hemolysis than plasma and IVIgG. The main advantage of convalescent plasma is, of course, that it does not require months to years of processing and development for new viral infections. But it probably carries the most serious safety concerns.
    CONFLICT OF INTEREST: None Reported
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    Results May Disappoint
    Giuliano Ramadori, Professor of Medicine | University Clinic, Internal Medicine ,Göttingen, Germany
    Mary Marovich and her coauthors (1) convincingly report about the hopes attributed to vaccines and/or monoclonal neutralizing antibodies for prevention or treatment of a COVID-19 infection. The authors also draw attention to possible problems in demonstrating efficacy of such antibodies in clinical trials.

    In fact, neutralizing antibodies may prevent cellular invasion in vitro but may not have any efficacy in vivo. It is known that viral hepatitis C-RNA may be detected together with neutralizing antibodies in the blood of infected persons.We also still do not have a vaccine against HCV nor against HIV, both RNA-viruses.
    The efficacy of the influenza vaccine also seems to be doubtful according to recently published work (2); the number of patients hospitalized with influenza-induced pneumonia was similar, independently of the vaccination status (2).

    On the other hand, authors also suggest that supportive measures in symptomatic COVID-19-infected patients may even be more effective than many more expensive therapeutic options (3). 

    REFERENCES
    1. Marovich M,Mascola JR,Cohen MS:Monoclonal antibodies for prevention and treatment of COVID-19.JAMA 2020,June 15
    2. Chow EJ,Rolfes MA, O´Halloran M et al.Respiratory and Nonrespiratory diagnoses associated with influenza in hospitalized adults. JAMA Network Open 2020;3(3):e201323
    3. Sun Q,Qiu H, Huang M,Yang Yi. Lower mortality of COVID-19 by early recognition and intervention: experience from Jiangsu Province. Ann Intensive Care2020;10:33 doi.org/10.1186/s13613-020-00650-2
    CONFLICT OF INTEREST: None Reported
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    Professor and Head of Department of Neurology
    Khichar Shubhakaran, D.M. ()Neurology | Dr.S. N. Medical College, Jodhpur, India
    Monoclonal antibodies may be promising but the cost all over the world is a big concern, especially in the time of collapsing economy all over the world.
    CONFLICT OF INTEREST: None Reported
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