Scientists develop protocols to use the plasma from recovered patients in the treatment of severe cases of COVID-19

The task is undertaken by a group that calls itself CPC-19 (Convalescent Plasma COVID-19) and comprises more than sixty professionals –most of them Argentine, some of whom live in the United States-. The team, which is led by researcher Laura Bover of the M.D. Anderson Cancer Center of Houston (Texas, United States) currently works on emergency protocols to use the plasma (that is rich in specific antibodies) from patients recovered from Coronavirus SARS–CoV-2 to be used in the treatment of severe cases of COVID-19 that do not respond to therapies approved by the Ministry of Health of Argentina.

This therapeutic strategy was used before in Argentina and in the world to face other pandemics (in some cases really successful) and is being used in countries such a as China, United States and Italy to treat COVID-19 cases. In the group, there are experts of various areas of science and medicine such as biochemists, hemotherapists, infectologists, virologists, epidemiologists, immunologists as well as lawyers who provide advice on the legal matters of the protocols.

From April 13^th, at the group’s website it is possible to download the convalescent plasma donation protocol (as it is called the plasma of recovered patients) and the plasma transfusion protocol for clinical use for severe cases of the disease.  The protocols, as well as the informed consent signed by the patients who will receive the treatment, were sent on Tuesday, April 14th, to the ‘Dirección de Sangre y Hemoderivados (DSH), under the scope of the National Ministry of Health. “From there, we hope that the regulations that allow their application in the different health centers that they attend be issued,” Bover explains. This will organize the logistics in the institutions adapting the protocols and submitting them to evaluation by the Ethics Committees, in order to obtain the approvals of the pertinent regulatory entities and prepare their applications.

“For this study, our starting point was the protocols that Dr. Arturo Casadevall, physician and researcher of the John Hopkins University (Baltimore, United States), generously made public,” says Bover, who was of CONICET between 1979 and 2002.

The donation protocol establishes that it should be done through what is known as plasmapheresis, a technology to extract blood and isolate plasma (soluble part of the blood) from the cells to return the latter to the donor. In this way, the patient does not see a decrease in the amount of white blood cells and red blood cells present in their body.

 Convalescent plasma antibodies

“About a week or little more after having being infected with SARS-CoV-2, the immunological system of a person starts to develop antibodies that, among other functions, are aimed at blocking the entry of the virus to the cells and, finally, eliminating it. Once recovered from the infection, despite no longer having the pathogen in its organism, the person can still have the specific antibodies in the blood to neutralize it. This plasma can be used to transfuse critically ill patients that do not respond to other treatments,” Rabinovich explains. He is a CONICET researcher at the Institute of Biology and Experimental Medicine (IBYME, CONICET), expert in immunology and member of the CPC-19 leading group.

According to the donation protocol, and to ensure that a person who had COVID-19 is recovered, it is necessary to have to consecutive negative results in the reverse transcription polymerase chain reaction (RT-PCR), the validated molecular diagnosis technique used by ANLIS/Malbrán and decentralized laboratories.

Then, to know if the plasma from this potential donor can be useful for a therapeutic treatment, initially it is necessary to make sure that it has specific antibodies against SARS-CoV-2, and this can be known through the rapid diagnosis kits that under the test strip format works similarly to pregnancy tests. This test can be added to previous proficiency studies being done to any potential blood donor. Gabriel Rabinovich works with Jorge Geffner, CONICET researcher at the Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS, CONICET-UBA), on the identification of the best tests available in the world to determine these values.

Once a plasma is known to have specific antibodies, it is necessary to ensure that it exceeds a certain threshold in amount, because if the level of antibodies is low it will probably not be effective. Andrea Gamarnik, CONICET researcher at the Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA, CONICET- Fundación Instituto Leloir) and also member of CPC-19, currently works with her team on the development of a test that allows titration (that is quatification) of the amount of antibodies specific for SARS-CoV-2 present in the plasma. The principle of operation of these tests is the same as the one of the rapid diagnosis kits but provide more accurate data.

Finally, a neutralization test is conducted to evaluate if those antibodies effectively serve to block the virus. “There are cases in which a convalescent plasma can have a high titer of specific antibodies against one infection but they are not neutralizing. For this reason, if possible, it is important to test them before applying them to critically ill patients in a therapeutical way,” Rabinovich explains.

For neutralization tests, it is possible to work with the live virus –only in the case of having laboratories with biosafety areas of level 3 or higher. Alternatively, experts can use pseudoviruses or pseudotyped viruses, which are innocuous viral particles (that means that they do not possess replication and infection capacity) since they do not have genetic material, but they express the protein of the viral “crown” which allows the virus to interact with the cells of the organism and induce, for instance, lung damage. Neutralizing antibodies will prevent that interaction. These tests can be done in level 2 biosafety cabinets, which almost all laboratories have.

“Currently, one part of the group works on the development of pseudo-neutralization tests, since there are very few laboratories in Argentina with sufficient biosecurity requirements to use live viruses,” Bover explains.

The scientist’s idea is to be able to monitor the health centers that apply the suggested protocols in order to optimize and learn from them in the future.

“We think that as long as there are no effective drugs to fight COVIDE-19 or a vaccine to prevent it, it is a valid therapeutic alternative the transfusion of convalescent plasma with a high titer of neutralizing antibodies to critically ill patients that do not respond to other treatments,” Rabinovich concludes.

For more information on the protocols click in the following: https://www.groupcpc-19.com/