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At the press conference on February 13 in Hubei Province, Zhang Dingyu, the director of Wuhan Jinyintan Hospital, made the “plasma therapy” attract much attention.

“Rehabilitated patients have a large number of comprehensive antibodies against the virus. We hereby urge the patients who have recovered to actively come to the hospital, extend their arms, donate plasma, and work together Save patients who are still struggling with disease. “

Actually, the “Diagnosis and Treatment Plan for New Coronavirus Infected Pneumonia (trial version 5) issued by the National Health and Health Commission earlier on February 5 “, it is mentioned that the recovery of plasma can be used for severe and critical cases.

In the sixth edition of the diagnosis and treatment plan released today, the plasma treatment was emphasized for the recoverers, which is suitable for patients with rapid disease progression, severe and critically ill patients.

The fifth edition of the treatment plan for the treatment of severe and critically ill patients mentioned the “possible recovery plasma treatment”

People applicable to “Plasma Treatment for Rehabilitation People” mentioned in the sixth edition of the treatment plan and the specific treatment plan mentioned

But in many media and news reports, plasma and serum don’t seem to be well distinguished. Which one is the real life-saving straw? What is the difference between the two?

To understand the problem, you must start with understanding the blood.

Know your blood

For ordinary people, blood does not have a good meaning. Most people’s impressions of blood are based on the bright red exuding from the wounds, and they don’t have a deep understanding of blood itself.

Blood circulates in the cardiovascular system and mainly plays the role of transporting substances. Oxygen, carbon dioxide, hormones, cytokines, various nutrients and metabolites are all goods transported by the blood, and support and coordinate the normal operation of various organs of the body.

Front view of the human circulatory system (source: Wikipedia)

In terms of composition, blood is a fluid tissue composed of plasma and blood cells . The widely known red blood cells, white blood cells, and platelets belong to blood cells, which are responsible for transporting substances, resisting and maintaining blood vessels.

Red blood cells contain different types of antigens, which determine blood types in the usual sense, such as the ABO blood type and the RH blood type system. There are antibodies corresponding to the red blood cell surface antigens in the blood, so when directly treating with blood-free plasma or serum, it is also necessary to match the appropriate blood type.

Plasma is blood without blood cells. It is mainly composed of organic compounds such as water, various electrolytes, proteins, and some gases. Proteins, as macromolecular organics that function in the body, are also vital in plasma. A variety of proteins in plasma are collectively called plasma proteins , which mainly include albumin , globulin , and fibrinogen Three categories.

The difference between serum and plasma is mainly the third protein, fibrinogen, and its related coagulation process. When a wound occurs in a normal person, the blood vessels are damaged and the surface of the foreign body is (such as gauze covering the wound) will activate platelets step by step, triggering the mechanism of physiological hemostasis, Blood scabs can also form on the wound surface.

Schematic diagram of physiological hemostatic process

If this process is moved to a test tube, the test tube wall will also activate the blood coagulation machineSystem, and then form a blood clot containing all blood cells, the light yellow liquid that precipitates is serum. Therefore, the difference between serum and plasma is that the former reduces fibrinogen and some coagulation factors consumed during coagulation, but also increases a small amount of substances released by platelets during coagulation.

Although there are differences, in this treatment of neocoronary pneumonia, the blood of the rehabilitation patients really works specific immunoglobulins against neocoronavirus ; this is also the answer to the question in the title . As for serum and plasma, there is almost no difference in the treatment of coronavirus, but the preparation process is different.

It is not difficult to find that the various components in the blood are the key to treatment, and further processing into blood products will be more efficient.

Blood Therapy

Different from the “human blood buns” described by Mr. Lu Xun, in addition to transfusion of whole blood during acute excessive blood loss, modern medicine uses more blood products and treats them by injection. Such practices have been passed down to the present, from the drive of empiricism to the approval of rationalism.

In the “Chinese Biological Product Regulations” issued by the State Drug Administration, the definition of blood products is:


Plasma protein components or blood cell component products that are separated, purified, or made by recombinant DNA technology from healthy human plasma or specific immune human plasma Human albumin, human immunoglobulin, human coagulation factor Passive immune prevention.

The three plasma proteins mentioned above are the “main forces” of blood products.

Human blood albumin is mainly used to regulate plasma colloid osmotic pressure and expand blood volume, and can be used to treat severe burns and other diseases.


Clotting factors are used to stop bleeding in surgery or to treat coagulopathy.

whileThe recently reported “plasma therapy” and “serum therapy” belong to the other type- Immunoglobulins , both rely on the comprehensive antibody (ie immunoglobulin) to identify and kill pathogens such as viruses.

Registration of clinical trials using recovery plasma therapy (source: China Clinical Trial Registry)

When faced with infectious diseases such as new coronary pneumonia and SARS pneumonia for the time being, people often heal through their own immunity. During this process, the immune system produces a large amount of antibodies against viruses or other pathogens, and even after the patient recovers, some remain in the blood. So importing these antibodies into other patients can also help kill these pathogens.

In 1890, German doctor Emil Adolf von Behring (Emil Adolf von Behring) Injected into animals, and then extracted serum to make “antitoxin”.

Two years later, the same treatment was applied to human trials by Behring and successfully treated tetanus and diphtheria , two deadly infectious diseases. The “white” and “broken” in the diabetic vaccine that everyone has injected since their childhood refers to these two diseases, respectively.

In 1901, Belin also won the first Nobel Prize in Physiology or Medicine.

Emil Adolf von Behring (source: Baidu Encyclopedia)

Facing an epidemic, it is important to target pathogens, but this also requires a process.

When no pathogens can be found and other animals’ immune systems cannot be used to extract blood and serum, those who are lucky for the rest of their lives become a source of antibodies or “antitoxins.” Attempts to use whole blood or serum from rehabilitation patients have been made in historical events such as polio in 1910 and the Spanish pandemic in 1918.

Even in the 21st century, where modern medicine has made great strides, plasma therapy still works. Whether it is atypical pneumonia caused by the same coronavirus (SARS) and Middle East respiratory syndrome (MERS) , Ebola virus, which has a very high mortality rate, has been written into novels, and brought to the big screen. Plasma therapy has come in handy in the early stages of their outbreak.

Plasma therapy is mentioned in the episode “Blood Plague”

Straw

As an anonymous expert in an earlier article in “China Science Network” said: (New Crown Virus Plasma Therapy) is a life-saving straw, you canHelp, but only “straw”.

Though the thick straw roll gives inexplicable reliability (source: unsplash)

Based on the nature of its polyclonal antibodies, plasma therapy does work. But even so, the latest diagnosis and treatment plan is only applicable to patients with rapid progress, severe and critically ill patients. For mild patients, the relationship between the risks and benefits behind this therapy is open to question.

Even before going through a series of screening techniques to ensure that no other pathogens are present in the plasma used, the antibodies themselves are not foolproof.

Antibodies in plasma can resist viruses in two ways, one is neutralizing antibodies , which directly prevents the virus from invading cells; the other is non-neutralizing antibodies , It specifically mediates the corresponding immune response and destroys the virus. The latter is a potential source of security risks.

Before After SARS, why are these patients more desperate? “ In the article, the milk tree mentioned the concept of” immune storm “/” inflammatory storm “: a strong immune response will release a large number of cytokines, causing the body to over-react to many functions, such as the lungs Fibrosis. Therefore, the strong effect of antibody dependence cannot be ignored. If it appears, the effect of the antibody is counterproductive, it will increase the infection rate, worsen the disease, and even cause death.

A series of reactions after SARS infection (source: Zuo W et al.)

The concentration of antibodies in the blood varies from patient to patient. If one-to-one treatment is performed, the results are unstable and the efficacy cannot be evaluated correctly.

However, if mixed with blood donated plasma, it may cause dilution of antibody concentration, poor overall effect, and increase the probability of transmission of other pathogens in the blood.

There are obvious signs of wrong units at the red box (source: China Clinical Trial Registry)

In the current clinical trial application for patients with new coronary pneumonia in the recovery period, the antibody titer for therapeutic plasma is greater than 1:80. If required, enter 200-400ml for the patient. (4-5ml / kg) Plasma, the total blood volume of normal adults is equivalent to 7% -8% of body weight. Taking a 70kg adult as an example, the final antibody drop in the patient ’s body The degree is about 1: 4.5 or more, which is about 18 times diluted compared with the input plasma.

It has been reported that receiving plasma therapy in the rehabilitation period has a good effect, although in this clinical trial application, a multi-center, randomized, parallel-controlled trial design may make its judgment of the efficacy of plasma therapy itself less accurate. But in this special period, the judgment and selection of clinical doctors based on the actual situation is far more reliable than the text typed by the keyboard.