The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19.
TLDR
In this paper, the authors put forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount.Abstract:
Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).read more
Citations
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Early Outpatient Treatment for Covid-19 with Convalescent Plasma
TL;DR: In this article , the authors evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status.
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COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes
Daniele Focosi,Massimo Franchini,Liise Anne Pirofski,Thierry Burnouf,Nigel Paneth,Michael J. Joyner,Arturo Casadevall +6 more
TL;DR: A review of 30 available RCTs demonstrated that signals of efficacy were more likely if the CCP neutralizing titer was higher than 160 and the time to randomization was less than 9 days, demonstrating confusion for both clinicians and patients about the appropriate use of CCP.
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Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence
Stephen A. Klassen,Jonathon W. Senefeld,Katherine A. Senese,Patrick W. Johnson,Chad C. Wiggins,Sarah E. Baker,Noud van Helmond,Katelyn A. Bruno,Liise Anne Pirofski,Shmuel Shoham,Brenda J. Grossman,Jeffrey P. Henderson,R. Scott Wright,DeLisa Fairweather,Nigel Paneth,Rickey E. Carter,Arturo Casadevall,Michael J. Joyner +17 more
TL;DR: In this article, a meta-analytical approach was used to pool daily survival data from all controlled studies that reported Kaplan-Meier survival plots, and a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy was found that convalescent plasma transfusion was generally associated with greater patient survival.
Journal ArticleDOI
Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence
Stephen A. Klassen,Jonathon W. Senefeld,Katherine A. Senese,Patrick W. Johnson,Chad C. Wiggins,Sarah E. Baker,Noud van Helmond,Katelyn A. Bruno,Liise Anne Pirofski,Shmuel Shoham,Brenda J. Grossman,Jeffrey P. Henderson,R. Scott Wright,DeLisa Fairweather,Nigel Paneth,Rickey E. Carter,Arturo Casadevall,Michael J. Joyner +17 more
TL;DR: It is argued that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions and convalescent plasma should be implemented at the immediate onset of future infectious disease outbreaks.
Posted ContentDOI
COVID-19 Convalescent Plasma for the Treatment of Immunocompromised Patients: A Systematic Review and Meta-analysis
Jonathon W. Senefeld,Massimo Franchini,Carlo Mengoli,Mario Cruciani,Matteo Zani,E. Gorman,Daniele Focosi,Arturo Casadevall,Michael J. Joyner +8 more
TL;DR: A metanalysis showed a risk ratio for mortality of 0.61 in treatment with CCP versus standard of care for immunosuppressed COVID-19 patients, and encourages initiation of high-titer CCP from vaccinees (hybrid plasma) in immunocompromised patients.
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Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies.
Alina Baum,Benjamin O. Fulton,Elzbieta Wloga,Richard Copin,Kristen E. Pascal,Vincenzo Russo,Stephanie Giordano,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Gurinder S. Atwal,Andrew J. Murphy,Neil Stahl,George D. Yancopoulos,Christos A. Kyratsous +15 more
TL;DR: This work investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails.
Journal ArticleDOI
Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial.
Ling Li,Zhang Wei,Yu Hu,Xunliang Tong,Shangen Zheng,Juntao Yang,Yujie Kong,Lili Ren,Qing Wei,Heng Mei,Caiying Hu,Cuihua Tao,Ru Yang,Jue Wang,Yongpei Yu,Guo Yong,Xiaoxiong Wu,Zhihua Xu,Li Zeng,Nian Xiong,Lifeng Chen,Juan Wang,Ning Man,Yu Liu,Haixia Xu,E. Deng,Xuejun Zhang,Chenyue Li,Conghui Wang,Shisheng Su,Linqi Zhang,Jianwei Wang,Yanyun Wu,Zhong Liu +33 more
TL;DR: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days.
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