The history of the use of convalescent plasma as a disease therapy goes back more than a century, when Emil Behring received the first Nobel Prize in Physiology and Medicine for his work demonstrating that plasma can be used to treat diphtheria.
It has then been reused to combat coronavirus-like outbreaks, such as SARS during 2003 and for the 2003-2006 Ebola virus. However, none of these cases have conducted large-scale clinical studies that can verify the effectiveness of clinical studies, although promising reports have been made that have given way to the World Health Organization (WHO) preparing guidelines on the appropriate use of plasma from recovered patients.
Now, this treatment brings new hope. The mechanism is to make plasma transfusions from patients who have already recovered from coronavirus to those with the disease. Plasma is the yellow liquid left after red blood cells, platelets, and other blood components are removed, and is made up of water, salts, antibodies, and other proteins.
It is usually used in therapies for people with immune system deficiencies, hemophilia or who have suffered trauma such as burns or rabies animal bites. Before antibiotics it was also used to fight bacterial infections.
The secret is in the antibodies
When we get sick, our immune system produces antibodies to defend against infection. Once recovered, these antibodies are stored in the plasma for weeks, even years. Then, convalescent plasma transfusion therapy involves the patient receiving these antibodies formed in someone else’s body before theirs has produced them.
«When convalescent plasma is given to a person susceptible to Covid-19, these antibodies will circulate in the blood, reach tissues, and mitigate the severity of the infection. Depending on the amount and composition of antibodies, the protection afforded by transferred immunoglobulin can last from weeks to months, achieving in many cases good clinical response as well as reducing the stay of hospitalization with good tolerance,» explained to Infobae Miriam María Méndez, head of the Hemotherapy Service of the Argentine German Hospital.
Several countries are testing this therapy, including Argentina and Chile. But initial studies with convalescent plasma treatment have been limited, mainly in a context where antibodies that can be injected through vaccines and help accelerate the fight against infection have not yet occurred.
They have been performed with a maximum of 10 patients and without any control, who are those who only receive placebo and who serve to compare the response with those who received the treatment. Despite this, they are considered promising, each has concluded that plasma therapy is safe and improves the patient’s outcome, as well as showing few adverse effects so far.
«Considering risk-benefit assessments, they present very good index which places them as very promising treatments in the fight against the effects that Covid-19 is causing so far,» explained Stephan Jarpa, former director of the Institute of Public Health (ISP) and director of regulatory agency InHouse.
More elaborate research is currently underway with this treatment. According to Celltrials.org, as of May 12, 1,065 clinical studies were being conducted by international health institutions to combat covid-19, 78 of this total are with convalescent plasma. Two of these investigations are being carried out in Chile, by the Pontifical Catholic University and by the Arturo López Pérez Foundation (Falp).
The function of these studies is to verify the effectiveness and safety of this treatment for coronavirus by monitoring patients, as well as determining whether it is rather a preventive treatment or whether it is more effective at some specific stage of the disease.
Plasma is obtained through a procedure called apheresis, which involves using a machine, which, through disposable and single-use equipment, allows the separation of the different components of the blood: red blood cells, platelets and plasma. The latter is extracted in a volume to be defined at each donor through the puncture of one vein in the arm, through another vein simultaneously, returns the rest of the red blood cells and platelets. This extraction is replaced with an equivalent volume physiological solution.
Despite the success in the tests that have been carried out, there are still theoretical concerns around this mechanism. One of these is that the artificial supply of antibodies can worsen an infection. This is due to a phenomenon called antibody-dependent enhancement (ADE). Antibodies that bind to a virus can be captured by cells that express antibody receptors, which could allow the virus to enter cells that are not normally susceptible to infection, and may increase the number of new viral particles produced. Another concern is that preformed antibodies may block the immune response itself to prevent it from responding properly.
It is recommended that this mechanism be used in covid-19 patients who are at high risk or who have signs of worsening. It is important to note that plasma must be compatible with the receptor’s blood group, to avoid side effects, in addition to verifying that the blood does not have other infections that can be transmitted. Another limitation is found in elderly patients who have weakened heart and lungs, as they may have difficulty tolerating a high-volume transfusion, which can lead to a complication known as transfusion-associated circulatory overload.
Although there are some hospitals in New York or China that have already tried these treatments, it is still considered to be in an experimental stage. To conduct the studies has increased the application for plasma donations from recovered patients, following some requirements specified by each facility. Specialists believe that the most important thing is to conduct controlled clinical studies (with patients receiving placebo) to see that it is indeed a safe and effective mechanism to combat covid-19, as it could be a way to change the current course of the pandemic.