The Hematology and Hemotherapy Center at the State University of Campinas (Unicamp) is expected to soon begin collecting blood plasma from people who have recovered from Covid-19, a respiratory infection caused by the new coronavirus (Sars-CoV-2), and using it it in a research protocol involving the treatment of individuals with the disease at the University's Hospital de Clínicas da Faculdade de Ciências Médicas (FCM) and also at other hospitals in the region. If the results are positive, this could be an option to treat patients at a moderate stage of the disease.
Plasma is the liquid part of the blood and makes up about 60% of its total content — the other components are white blood cells, red cells and platelets. Its use has been considered a possible strategy to provide the necessary antibodies to those who do not yet have them at levels capable of protecting them from Covid-19. Although it is not a risk-free process, it is estimated that plasma transfusion can lead to a reduction in the viral load in the body and an improvement in symptoms, or the clinical evolution of patients. In the assessment of the National Health Surveillance Agency (Anvisa), “the strategy can be quickly accessible, as there is a sufficient number of people who have recovered from the disease and who can donate plasma containing immunoglobulins that react against the Sars-CoV virus -two".
The project coordinated by doctors and researchers from Unicamp's Blood Center was submitted for analysis by the National Research Ethics Commission (Conep) on April 3, shortly after the United States food and drug regulatory agency, the FDA, had authorized the use of therapy, on an experimental basis, in people infected with the virus in serious condition — those admitted to intensive care units (ICU), with respiratory failure, who, therefore, can only breathe with the help of devices .
If approved by Conep, the institution will be another Brazilian public university to test this strategy in the treatment of people with Covid-19 in the country. On April 4, a consortium involving the Albert Einstein and Sírio-Libanês hospitals and the Faculty of Medicine of the University of São Paulo (FM-USP) received authorization from the commission to begin testing plasma on people infected with the new coronavirus in serious condition. On April 6, the Blood Center of Ribeirão Preto also began the process of collecting blood plasma from patients cured of Covid-19 for the treatment of individuals in a critical condition of the disease at the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto at USP.
The idea of doctors and researchers at Unicamp's Blood Center, however, is different. The objective is to analyze the effectiveness of the strategy in treating people with a moderate clinical picture of the disease, that is, who can still breathe without the help of devices. “We are going to set up two groups”, explains Marcelo Addas Carvalho, a doctor at the Unicamp Blood Center and one of the project coordinators. “One of them will receive blood plasma with antibodies specific to Sars-CoV-2 while the other, used as a control group, will receive plasma without antibodies to the new coronavirus.” They intend to compare the evolution of the clinical condition of individuals in the two groups and, at the same time, try to contain the deterioration of these people's health conditions, avoiding their admission to the hospital's ICU. The limited number of intensive care spaces is one of the main bottlenecks in the healthcare system when dealing with the growing number of Covid-19 patients.
Ancient therapy
The use of blood plasma in treating diseases is not new. On the contrary. This therapeutic strategy has been used several times throughout history in outbreaks of other respiratory infections, including in recent epidemics caused by other viruses in the coronavirus family, such as the epidemics of Acute Respiratory Syndrome (Sars), in 2003, and that of Respiratory Syndrome of the Middle East (Mers), in 2012. The therapy was also tested in outbreaks of measles and mumps — before the existence of vaccines for these diseases —, in addition to the Ebola outbreak, in 2014, and the Spanish flu pandemic, in 1918 .
In the case of the Covid-19 pandemic, studies published in recent weeks have highlighted the therapeutic potential of blood plasma transfusion in individuals infected with Sars-CoV-2 — even though these studies, for the most part, involve small samples of people. The most recent, published on March 27 in the Journal of the American Medical Association (JAMA), involved five people aged between 36 and 65 years. They all had Covid-19, had severe pneumonia, a high viral load and were breathing with the help of devices.
Patients received plasma with specific antibodies for Sars-CoV-2 10 to 22 days after being admitted to a hospital in Shenzhen, China. The donors, aged 18 to 60, had recovered from the infection and agreed to donate blood for research. Three of the five patients who received the plasma began breathing again without the help of machines two weeks after the transfusion and were discharged after about 50 days in the hospital. The other two were in stable condition 37 days after transfusion. As they also received antiviral medications, it is not known which therapy would have been more decisive in improving their clinical condition.
Risks
In Campinas, the strategy of the team of doctors and researchers at Unicamp's Blood Center will be to contact people who have recovered from Covid-19 after treatment at the university's Hospital de Clínicas and other hospitals in the region and invite them to the Donation. “Plasma collection will be carried out in cured patients 30 days after the disappearance of all symptoms”, explains doctor Carolina Costa-Lima Salmoiraghi, one of the coordinators of the project, which, in addition to Carvalho, also involves doctor Bruno Deltreggia Benites. After this first screening, donors will undergo apheresis, a procedure in which automated equipment separates the plasma from the other blood components, which are then returned to the donor. According to Costa-Lima, each person will be able to donate 600 milliliters of plasma, “enough to care for up to three patients infected with Sars-CoV-2”.
Convalescent plasma transfusions are generally safe and well tolerated by most people undergoing this procedure. Still, caution is needed regarding its use in the treatment of Covid-19. In addition to the available studies not being sufficient to attest to the effectiveness of the therapy against the disease, there is a risk, although relatively rare, that people who received the plasma may have allergic reactions and other adverse events. One of the most serious in these cases is transfusion-related acute lung injury (Trali), characterized by acute respiratory failure, pulmonary edema and low oxygen concentration in arterial blood.
Trali can occur during or up to six hours after plasma transfusion. Available evidence suggests that it can be triggered by the transfusion of plasma from female donors who have had children, which contain specific antibodies that are sometimes harmful to others. “To avoid this risk”, explains Costa-Lima, “we will only focus on male donors and women who have never had children”.
Scientific Articles
SHEN, C. et al. Treatment of 5 critically ill patients with Covid-19 with convalescent plasma. Journal of the American Medical Association. sea. 2020.
CASADEVALL, A. & PIROFSKI, L. The convalescent will be an option for containing Covid-19. The Journal of Clinical Investigation. sea. 2020.
Published article originally in Revista Pesquisa Fapesp.