(Combating New Coronary Pneumonia) Experts Talk about Safety Risks of Plasma Therapy: Choosing the Right People at the Right Time

China News Service, Beijing, February 24th (Reporter Sun Zifa) In response to the outbreak of pneumonia caused by new coronavirus infection, the latest version of the diagnosis and treatment program has added "recovery plasma treatment" to the treatment of severe and critical cases. The action of "save thousands of people", with the continuous increase in the number of patients who have been cured and discharged from hospitals, and active response, plasma therapy has attracted much attention.

Member of the Standing Committee of the Microcirculation and Blood Therapy Professional Committee of the Chinese Society of Microcirculation and Professor Pan Leiting, School of Physical Sciences, Nankai University, reminded him through a web interview organized by the Chinese Association of Science and Technology that plasma therapy has safety risks. "It must be used dialectically. The right people. "

Plasma therapy is the introduction of foreign antibodies to kill and neutralize the virus

According to Pan Leiting Science, plasma is the whole blood leaving the blood vessel after anticoagulation treatment, and then centrifuged to obtain a cell-free liquid, which is rich in plasma proteins and various antibodies. An important mechanism for the body to deal with the virus is to produce antibodies to bind the virus and then kill the virus. After recovering from most patients with neocoronary pneumonia, specific antibodies against neocoronavirus will be produced in the body's blood. Plasma from the recovered person will be imported into the patient's body. That is, foreign antibodies will be introduced to help the patient kill and neutralize the virus.

Antibodies can be divided into neutral antibodies and non-neutralizing antibodies according to their mechanism of action. Antibodies against the S protein of neocrown virus are neutralizing antibodies. They bind to the S protein on the surface of the virus and block the binding of S protein to the ACE2 protein receptor. , Thus blocking the virus from entering cells; non-neutralizing antibodies are antibodies against viral envelope proteins or membrane proteins, which, when combined with corresponding proteins on the surface of the virus, do not affect the S protein to mediate the virus into the lung epithelial cells, but rely on Immune mechanism mediates phagocytic immune cells-macrophages phagocytose viruses.

It can be seen that neutralizing antibodies in plasma are the most needed antibodies for treatment. Neutralizing antibodies directly exert antiviral effects through physical obstacles. They are the main force for antibodies to exert antiviral effects. Non-neutralizing antibodies are indirectly cleared. virus.

Watch out for non-neutralizing antibodies "abducted" by the virus

Pan Lei Ting pointed out that we must be alert to the fact that non-neutralizing antibodies can sometimes be "abducted" by the virus to "help". Under normal circumstances, after being engulfed by macrophages, the virus is encapsulated in endosome vesicles, and then the endosomes move away from the cell surface and move into the cell. In the process, the virus fuses with lysosome vesicles, and lysosomes The body contains a variety of hydrolases that can hydrolyze viruses.

However, the virus is constantly evolving, using all means to escape phagocytosis. For example, after the virus is swallowed, it will try to remove the outer envelope and expose the viral nucleic acid, and then transfer the nucleic acid from the endosome to macrophage. In the cytoplasm of the cell, the viral nucleic acid replicates and assembles into new viral particles and is released outside the cell. In this way, the virus uses such non-neutralizing antibodies to turn immune cells into host of the virus, turning the enemy into friends, escaping immune killing and achieving self-amplification.

"The intracellular expansion of viruses in macrophages may not be the worst thing. Worse still, viruses may promote macrophages to promote inflammatory storms." In the early stages of virus infection, macrophages were functional in all aspects. Phagocytosis and hydrolysis of antibody-mediated viruses. In the later period, macrophages not only sensed viral signals, but also various cytokine signals, and their functions changed. The virus took advantage of the opportunity to escape lysosomal killing, and a large number of macrophages were amplified. The virus in turn strongly activates macrophages, which in turn releases excessive amounts of pro-inflammatory factors, causing damage to lung tissue. "It is not difficult to see that the non-neutralizing antibodies in the plasma may have adverse effects, especially in the later stages of the disease, exacerbating the storm of inflammation." He said.

Safety risk points include both patients and recoverers

Pan Leiting believes that in the absence of a vaccine, plasma is an alternative method for the treatment of new coronary pneumonia, but it is a niche treatment method. The first is that the number of cured patients is far less than that of patients, and not the plasma of each cured person. Both can be used, so the amount of available plasma is very limited. Second, due to the complexity of the immune system, there are a series of uncertain factors in the input of other people's plasma, which may exacerbate the body damage of patients in the later stages of the disease. At present, plasma therapy is mainly effective for critically ill patients, and its effect on critically ill patients is very limited. In the absence of better treatment, borrowing the plasma of the recovering person can be said to be the last line of defense. "There is no way."

He pointed out that the safety risks of plasma therapy are divided into two aspects: patients and recoverers. For patients, first, the patient population must be selective, such as patients who are too old, have severe underlying diseases, or are allergic to plasma; It is used during the appropriate course of the patient's life. Once the "inflammatory storm" occurs in the patient, the patient's heart, liver, kidney and other organs are damaged and fail. If plasma antibodies are input again at this time, the inflammation storm may be accelerated and the organs may be aggravated. Damage; Third, pay attention to blood group matching for plasma input to avoid hemolysis caused by lysis of red blood cells of the recipient.

For the rehabilitated patients, one should pay attention to whether the plasma virus in the rehabilitated patients is discharged. Generally, the patients' rehabilitation means that no new crown virus can be detected, but it does not mean that they are completely free of the virus. Avoid cross infection. In principle, two weeks after discharge from hospital, it is confirmed that there is no new coronavirus in the body, and about 400 ml of plasma can be donated for clinical treatment. Ideally, the patients should be aged 18-55 years old, without basic diseases and other infectious diseases, and have normal blood glucose and lipids. .

Pan Leiting said that since the development of the epidemic, thanks to basic scientific research and clinical observation and pathological research, the academic community has become more and more aware of the new crown virus itself and the diseases it causes. He emphasized, "From the perspective of the report, the trend is good, but the task of (prevention and control of epidemic situation) is still arduous, and we must not relax our vigilance. The new crown virus is highly contagious, and if it is not properly controlled, it will resurrect. (Finish)