Convalescent plasma therapy, often referred to as passive antibody therapy, constitutes a therapeutic intervention wherein blood plasma derived from individuals convalescing from a specific infectious ailment is employed to treat contemporaneously afflicted patients. The principal objective of this therapy lies in conferring immediate passive immunity to the recipient by means of preformed antibodies against the causative pathogen, thereby potentially ameliorating the course of the ongoing malady.
The genesis of convalescent plasma therapy can be traced to the latter part of the 19th century, finding its inaugural application during the ravages of the Spanish flu pandemic in 1918. Since its inception, this therapeutic modality has been invoked in a spectrum of infectious disease outbreaks, encompassing the H1N1 influenza pandemic of 2009, the Ebola virus scourge in West Africa in 2014, and most recently, amidst the global COVID-19 pandemic.
Convalescent plasma is culled from individuals convalescent from the targeted infectious malady. This plasma component is enriched with antibodies, specialized proteins elicited by the immune system in response to the presence of a particular pathogenic entity. When introduced into a patient harboring an active infection, these antibodies function as vigilant sentinels, effecting the neutralization of the pathogen, impeding its replicative capacity, and buttressing the host's immune riposte.
The acquisition of convalescent plasma entails a methodical procedure. Convalescent individuals are subjected to stringent screening criteria to ensure eligibility, encompassing requisite antibody titers and the absence of concurrent infectious agents. Subsequently, plasma is garnered through the process of plasmapheresis, wherein blood is drawn, plasma is segregated from cellular constituents, and the latter are subsequently returned to the donor.
Convalescent plasma therapy finds its principal application in the combat against viral infections, typically resorted to when alternative therapeutic modalities are constrained or unavailable. It has garnered notable successes in the context of influenza, Ebola, and most prominently, amidst the formidable COVID-19 pandemic.
The efficacy of convalescent plasma therapy remains a subject of sustained scientific inquiry and discourse. Its potency is contingent upon multifarious factors, including the specific infectious agent, the temporality of administration, and the quality of the procured plasma.
In 2019, a new type of coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to the outbreak of coronavirus disease 2019 (COVID-19), rapidly spreading worldwide after its initial identification in Wuhan, China. In the early months of 2020, the application of convalescent plasma began in specific cases and small-scale instances in both China and Italy. 1) 2) See the great work that was done by Giuseppe De Donno and his colleagues in Italy in the hospitals of Mantua and Pavia. 3) The broader implementation of convalescent plasma therapy in the United States was facilitated through a Mayo Clinic-led Expanded Access Program for convalescent plasma, 4) followed by an Emergency Use Authorization granted by the United States Food & Drug Administration. 5) Data derived from the Expanded Access Program indicated that patients not requiring mechanical ventilation who received high-titer convalescent plasma exhibited lower mortality rates compared to those administered low-titer convalescent plasma (14.2% vs. 22.2%). 6)
During the initial stages of the pandemic, several randomized controlled trials concluded that convalescent plasma therapy was not effective for COVID-19. Notably, most of these trials focused on patients who were already seropositive or in the advanced stages of the disease and/or used plasma units with inadequate antibody levels. 7) 8) 9) 10) 11) 12) Conversely, randomized controlled trials that directed their attention towards the early administration of high-titer convalescent plasma following diagnosis demonstrated a substantial reduction in hospital admissions, ranging from approximately 50-80%. 13) 14) This outcome aligns with the effectiveness achieved with monoclonal antibodies and small-molecule antiviral agents. 15)
An epidemiological analysis examining the utilization of convalescent plasma and subsequent mortality rates in the United States revealed a robust inverse correlation, presenting compelling evidence of its effectiveness at a population-wide level. Based on this data, it was estimated that the deployment of convalescent plasma potentially averted roughly 100,000 fatalities in the United States. 16)