The highly infectious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, has infected more than 517 million people worldwide and more than 6.25 million victim killed . Significant efforts have been made by scientists to develop therapies aimed at reducing death rates associated with severe COVID-19 infection.
Study: Outpatient early treatment of Covid-19 with convalescent plasma. Photo Credit: Cryptographer/Shutterstock
Currently, three monoclonal antibody therapies have received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for use in outpatients. Previous reports have shown that when these therapies were given to patients with COVID-19 between five and seven days after symptom onset, there was a significant reduction in disease progression and hospitalization.
The researchers said there is a need for alternative therapies for outpatients because monoclonal antibody treatments are unavailable or rare in many low- and middle-income countries, and some therapies have proven ineffective against certain variants of SARS-CoV-2 .
A previous study reported that early treatment of hospitalized patients with high COVID-19 convalescent plasma levels showed a 50 percent reduction in mortality rates. However, randomized clinical trials have shown that the benefits of plasma treatments in patients hospitalized with severe COVID-19 infection are conflicting. Several studies have shown improved outcomes in patients with COVID-19 treated with high plasma titers within days of onset of symptoms.
The scientists pointed out that there is very little data from randomized trials related to outpatients with COVID-19 infection. However, a clinical trial of COVID-19 convalescent plasma treatment in outpatients in Argentina showed a significant reduction in the risk of disease progression to severe infection in participants treated within 72 hours of the onset of mild COVID-19 symptoms.
A new study
Researchers conducted a double-blind, multi-center, randomized, controlled trial known as the Convalescent Plasma to Limit SARS-CoV-2 Associated Complications Study to assess whether early treatment with COVID-19 plasma could reduce the progression of the illness and consequently the hospitalization rate. This study is available at New England Journal of Medicine.
In this study, researchers evaluated the effectiveness of the treatment regardless of the participants’ vaccination status. The study cohort consisted of participants who received a plasma transfusion within eight days of the onset of COVID-19 symptoms.
The study strongly suggests a reduction in hospitalizations when outpatients in their early phase of SARS-CoV-2 infection were treated with COVID-19 convalescent plasma. The result of this study is consistent with previous studies based on monoclonal antibody therapies, which showed significant efficacy when early administration of an optimal amount of pathogen-specific antibodies. In addition, another study reported that administration of a high dose of polyclonal plasma and monoclonal antibodies during the early phase of infection, i.e. within the first week after symptom onset, resulted in a significant reduction in the risk of disease progression.
All participants in this study were between the ages of 18 and 84 and received a transfusion within nine days of the onset of COVID-19 symptoms. In the study cohort, 44% of participants received a transfusion within five days of symptom onset. However, this scenario is more practical than administering plasma within 72 hours.
Interestingly, the results of the current study are consistent with previous studies that found early monoclonal antibody treatment reduced doctor visits by 59% for patients with COVID-19. The study also shows that convalescent plasma administration in the subgroup of COVID-19 outpatients within five days of symptom onset had better outcomes in reducing the risk of hospitalization than those administered within nine days of symptom onset were treated.
The scientists said monoclonal antibodies are expensive to produce and take a long time to develop. Because of this, these antibodies are not widely available. In contrast, COVID-19 plasma from convalescents in low- and middle-income countries is readily available and relatively inexpensive to produce. A single donor can provide multiple units of plasma that can be easily administered to COVID-19 patients. In addition, COVID-19 plasma from convalescents is less susceptible to antibody resistance and more potent against locally circulating variants. Therefore, plasma therapy can be considered an effective treatment for COVID-19.
challenges during the course
One of the biggest challenges the scientists faced during the study was the ever-changing treatment standards and available therapies. Another difficulty the authors faced was that they obtained the plasma for the study from donors who had recovered from infection with the original SARS-CoV-2 strain. However, during the study, the alpha and delta variants were dominant.
One of the strengths of this study is its diverse cohort, with participants from across the United States. The authors said plasma therapy could be beneficial in areas where the supply of COVID-19 vaccines is low. Also for future pandemics, convalescent plasma can initially be used to treat diseases until specific monoclonal therapies and vaccines are developed.