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

Abstract

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.

Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2

“…The success of these vaccines is thought to result in no small part to the potent antiviral activities of the antibodies they induce. While reinfections have been documented 2,3 , seropositivity and levels of neutralizing antibody are associated with highly reduced rates of re-infection [4][5][6] , and passive transfer of plasma from convalescent donors has shown therapeutic efficacy in some studies [7][8][9][10][11][12][13][14] but not others [15][16][17][18] . The inconsistent results with convalescent plasma studies suggest that the variables that contribute to passive antibody efficacy in polyclonal preparations are not completely understood.…”

Heterologous Hyperimmune Polyclonal Antibodies Against SARS-CoV-2: A Broad Coverage, Affordable, and Scalable Potential Immunotherapy for COVID-19

“…CP transfusion contributes to viral clearance and improves patient survival when administered promptly and has been therapeutically used worldwide during the COVID-19 pandemic in hospitalized patients ( 6 , 7 ). However, it is worth mentioning that in some developing countries CP transfusion may heighten the risk of transmission of blood-borne pathogens if proper donors screening and virus testing procedures are not applied ( 8 , 9 ).…”

“…However, it is worth mentioning that in some developing countries CP transfusion may heighten the risk of transmission of blood-borne pathogens if proper donors screening and virus testing procedures are not applied ( 8 , 9 ). Furthermore, uncertainty remains about the therapeutic efficacy of CP transfusion, as controlled clinical trials have provided variable results in terms of mortality and need for mechanical ventilation ( 7 ). The diversity among reported results is likely due to the heterogeneity of trial designs, anti-SARS-CoV-2 plasma titer variation, and differences in latency to product administration ( 7 ).…”

“…Furthermore, uncertainty remains about the therapeutic efficacy of CP transfusion, as controlled clinical trials have provided variable results in terms of mortality and need for mechanical ventilation ( 7 ). The diversity among reported results is likely due to the heterogeneity of trial designs, anti-SARS-CoV-2 plasma titer variation, and differences in latency to product administration ( 7 ). Therefore, more studies are required to establish the optimal doses and timing for CP transfusion to COVID-19 patients.…”

Convalescent Covid-19 plasma: Back-to-basics and ethics, and next steps

“…A year back, points to consider and questions were raised about applicability [6] , [7] , logistic issue, impact, safety and usefulness of plasma passive immunotherapy in Covid-19 patients [8] , [9] ; other issues dealing with ethics of plasma collection and allocation [10] , [11] , [12] , [13] , and best protocol scaling have been addressed, and some of these questions have been resolved. Large cohorts of treated patients versus controls have been scrutinized and results on efficacy were not as straightforward as initially expected [14] , [15] , [16] , [17] , [18] . An innumerable number of studies have been proposed for publication in journals of different specialties; as could have been anticipated, studies coming from almost unknown teams experienced difficulties to be published, contrary to the ones led by key opinion leaders.…”