Treatment of Severe COVID-19 with Convalescent Plasma in Bronx, NYC

Yoon, Hyunah; Bartash, Rachel; Gendlina, Inessa; Rivera, Johanna; Nakouzi, Antonio; Bortz, Robert H.; Wirchnianski, Ariel S.; Paroder, Monika; Fehn, Karen; Serrano-Rahman, Leana; Babb, Rachelle; Sarwar, Uzma; Haslwanter, Denise; Laudermilch, Ethan; Florez, Catalina; Dieterle, M. Eugenia; Jangra, Rohit K.; Fels, J. Maximilian; Tong, Karen; Mariano, Margarette C.; Vergnolle, Olivia; Georgiev, George I; Herrera, Natalia G.; Malonis, Ryan J.; Quiroz, Jose A.; Morano, Nicholas C.; Krause, Gregory J.; Sweeney, Joseph; Cowman, Kelsie; Allen, Shelby; Annam, Jayabhargav; Applebaum, Ariella; Barboto, Daniel; Khokhar, Ahmed; Lally, Brianna J.; Lee, Audrey; Lee, Max; Malaviya, Avinash; Sample, Reise; Yang, Xiuyi A.; Li, Yang; Ruíz, Rafael; Thota, Raja; Barnhill, Jason; Goldstein, D. Yitzchak; Uehlinger, Joan; Garforth, S.; Almo, Steven C.; Lai, Jonathan R.; Gil, Morayma Reyes; Fox, Amy; Chandran, Kartik; Wang, Tao; Daily, Johanna P.; Pirofski, Liise-anne

doi:10.1172/jci.insight.142270

Cited by 39 publications

(53 citation statements)

References 80 publications

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“…Qualitative inspection of the available Kaplan–Meier survival data from 16 controlled studies revealed a directionally consistent pattern whereby convalescent plasma transfusion was associated with greater patient survival compared to non-transfused patients ( Figure 1 ) ( 11 , 27 , 41 , 43 , 46 , 47 , 50 , 52 , 59 – 62 , 64 , 69 – 71 ). Pooling all available Kaplan–Meier survival data showed a 14% relative improvement in COVID-19 patient 28-day survival associated with convalescent plasma (84 vs. 74%) ( Figure 2A ).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 98%

“…To date, 11 RCTs ( 11 , 27 , 30 , 40 – 47 ) and 24 matched-control studies ( 3 , 4 , 48 – 69 ) have investigated convalescent plasma therapy for COVID-19. Of these studies, 16 presented survival data using a Kaplan–Meier diagram ( 11 , 27 , 41 , 43 , 46 , 47 , 50 , 52 , 59 – 62 , 64 , 69 – 71 ). To investigate the impact of convalescent plasma on COVID-19 patient survival over time, we extracted daily survival data from all available Kaplan–Meier diagrams using an online data extraction tool (WebPlotDigitizer v4.4, Pacifica, CA, USA).…”

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

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Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

et al. 2021

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Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue 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. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

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Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 98%

Section: Convalescent Plasma Therapy For Covid-19: Mosaic Of Clinical Evidencementioning

confidence: 99%

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

et al. 2021

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“…Given that a significant proportion of hospitalized patients progress to respiratory failure and convalescent plasma administration is associated with reduced mortality when given early in the course of disease, patients with COVID-19 should be viewed as candidates for convalescent plasma at the time of hospital admission. Although the window for antibody efficacy has not been defined thus far and may differ with age or disease severity (52), available data suggest that antibody-mediated antiviral efficacy early in the course of disease could avoid inflammatory pulmonary sequelae that compromise gas exchange. In contrast, late antibody administration is unlikely to affect organ damage mediated by overexuberant inflammatory responses (74).…”

Section: The Antibody Preparation Must Contain Antibody Specific For mentioning

confidence: 99%

“…Ageing, with its associated decline in immunity, may be another important variable affecting the efficacy of antibody-based therapy. Along these lines, CP was more effective in reducing mortality in severely ill patients with COVID-19 who were less than 65 years of age (52).…”

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confidence: 95%

The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

Casadevall

Pirofski

Joyner

2021

mBio

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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).

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“…All patients required supplemental oxygen, had a median WHO ordinal scale value of 5, and 48% of these patients required non-invasive positive pressure ventilation or mechanical ventilation at enrollment. Patients received 1 unit of 200mL CCP pre-screened for Spike IgG titer by ELISA (as described in Yoon et al 37 ) within 3 days of hospitalization (median day 1 of hospitalization) and were followed for up to 28 days after enrollment. Antibody profiling was performed on units of CCP, patients pre-CCP (day −1), one day after CCP (day 1), and 3 days after CCP (day 3).…”

Section: Resultsmentioning

confidence: 99%

Functional Antibodies in COVID-19 Convalescent Plasma

Herman

Wang

Loos

et al. 2021

Preprint

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In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.

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Treatment of Severe COVID-19 with Convalescent Plasma in Bronx, NYC

Cited by 39 publications

References 80 publications

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

Convalescent Plasma Therapy for COVID-19: A Graphical Mosaic of the Worldwide Evidence

The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

Functional Antibodies in COVID-19 Convalescent Plasma

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