The highly infectious severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, the causative agent of the coronavirus pandemic 2019 (COVID-19), has infected more than 517 million people and killed more than 6.25 millions of victims worldwide. Scientists have made considerable efforts to develop therapies aimed at reducing mortality rates associated with severe COVID-19 infection.
Study: Early outpatient treatment of Covid-19 with convalescent plasma. Image credit: Cryptographer / Shutterstock
Currently, three monoclonal antibody therapies have received Emergency Use Authorization (EUA) from the United States Food and Drug Administration (FDA) for use in outpatients. Previous reports have shown that if these therapies were given to patients with COVID-19 between five and seven days after symptom onset, a significant decrease in disease progression and hospitalization occurred.
The researchers said there is a need for alternative therapies for outpatients because in many low- and middle-income countries monoclonal antibody treatments are unavailable or rare, and some therapies have been shown to be ineffective against specific variants of SARS-CoV-2.
A previous study reported that early treatment of hospitalized patients with high COVID-19 convalescent plasma titer showed a 50% reduction in death rates. However, randomized clinical trials have shown that the benefits of plasma therapies in patients hospitalized with severe COVID-19 infection are inconsistent. Several studies have demonstrated improved outcomes in patients with COVID-19 treated with high plasma titer within days of symptom onset.
The scientists pointed out that there are very few data from randomized trials associated with outpatients with COVID-19 infection. However, a clinical trial of COVID-19 convalescent plasma treatment in outpatients in Argentina showed a significant decrease in the risk of disease progression to severe infection in participants treated within 72 hours of the onset of mild symptoms. of COVID-19.
A new study
Researchers conducted a double-blind, multicenter, 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 disease progression and, consequently, the rate of hospitalization. This study is available in the New England Journal of Medicine.
In this study, the researchers evaluated the effectiveness of the treatment independently of the vaccination status of the participants. The study cohort consisted of participants who received a plasma transfusion within eight days of onset of COVID-19 symptoms.
The study strongly indicated a reduction in hospitalization 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 trials based on monoclonal antibody therapies, which showed significant efficacy when given early administration of an optimal amount of pathogen-specific antibodies. In addition, another study also reported that when a high dose of polyclonal plasma and monoclonal antibodies was administered during the early phase of infection, i.e. within the first week after the onset of symptoms, it resulted in a substantial reduction in the risk of disease progression.
All participants in this trial were between the ages of eighteen and eighty-four 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 the onset of symptoms. However, this scenario is more practical than administering plasma within 72 hours.
Interestingly, the results of the current study are consistent with previous trials that found early monoclonal antibody treatment reduced medical visits for patients with COVID-19 by 59%. The study also indicates that the administration of convalescent plasma in the subgroup of outpatient COVID-19 patients within five days of the onset of symptoms had better results in reducing the risk of hospitalization than those who received treatment within nine days of symptom onset.
The scientists said monoclonal antibodies are expensive to manufacture and take considerable time to develop. This is the reason why these antibodies are not widely available. In contrast, COVID-19 convalescent plasma is readily available in low- and middle-income countries and relatively inexpensive to produce. A single donor can provide multiple units of plasma, which can be easily administered to COVID-19 patients. Additionally, convalescent COVID-19 plasma is less vulnerable to antibody resistance and more effective against locally circulating variants. As such, plasma therapy can be considered a powerful treatment for COVID-19.
Challenges encountered during the study
One of the main challenges faced by the scientists during the study was the ever-changing standards of care and available therapies. Another difficulty the authors faced is that they obtained the plasma for the study from donors who recovered from infection with the original strain of SARS-CoV-2. However, during the study, the Alpha and Delta variants became dominant.
One of the strengths of this study is its diverse cohort containing participants from across the United States. The authors said plasma therapy could be beneficial in areas where the COVID-19 vaccine supply is low. Even for future pandemics, convalescent plasma can be used initially for the treatment of disease until specific monoclonal therapies and vaccines are developed.