To understand the adverse reactions of vaccines, just read this article

The key to enhancing confidence in vaccination is to make everyone understand the mechanism of action of the vaccine as much as possible, publish as much relevant data on vaccination as possible, and let everyone know that the benefits of the vaccine far outweigh the risks.

Written by | Alalei (Master of Internal Medicine, Tongji University School of Medicine)

On February 25, 2021, two more domestically produced COVID-19 vaccines were approved for marketing by the National Medical Products Administration (NMPA), namely CanSino Biologics' recombinant COVID-19 vaccine (adenovirus type 5 vector) and Sinopharm Wuhan Biopharm's inactivated COVID-19 vaccine (Vero cell). So far, my country has officially announced four COVID-19 vaccines. On the same day, Fosun Pharma and BioNTech's mRNA COVID-19 vaccine (Note: Pfizer/BioNTech's mRNA vaccine, Fosun Pharma has obtained authorization for the vaccine in China) also obtained special import approval from the Health Bureau of the Macao Special Administrative Region of China. With the approval of multiple COVID-19 vaccines, humans will usher in a new situation in the fight against the COVID-19 pandemic.

A considerable number of people at home and abroad have been vaccinated with the COVID-19 vaccine, and data on its effectiveness and safety have been released one after another, with promising results. However, for more people, compared with the protective power of the vaccine, reports of adverse reactions to the vaccine, especially severe adverse reactions, are more likely to touch their nerves. To get vaccinated or not, that is the question!

Why do adverse reactions occur after vaccination?

Let's start with the types of immunity.

Immunity can be divided into two categories:

1. Nonspecific Immunity

Also known as natural immunity or innate immunity, it is a natural defense mechanism that the body is born with. It is not unique to a certain individual, nor does it work specifically against a certain antigenic "foreign body". This type of immunity "does not remember" and will have a similar reaction if it is exposed to the same antigen again. We call it "lack of immune memory."

The nonspecific immune system includes: 1. Immune barriers such as skin and mucous membranes; 2. Immune molecules such as lysozyme, acute phase proteins, complement, and cytokines; 3. Immune cells such as macrophages and monocytes.

2. Specific Immunity

The so-called "specificity" means "specifically targeting". Lymphocytes can specifically identify antigenic "foreign bodies", and then activate, proliferate and differentiate themselves, secrete specific antibodies, and eliminate "foreign bodies" and damaged cells.

This is an acquired immunity, which is divided into cellular immunity and humoral immunity. The former is mediated by T lymphocytes; the latter is mediated by antibodies. Antibodies are immune effector molecules synthesized and secreted by B lymphocytes.

The immune response after vaccination is to make the human body produce specific resistance to a certain pathogenic microorganism and have immune memory. In other words, the human body can "remember" the disease it has had, and after contacting the same antigen again, it can cause a rapid and strong immune response, thereby exerting a protective effect.

Adverse reactions after vaccination

From the two types of immunity

1. Nonspecific immune damage

After vaccination, some people will experience redness and swelling at the injection site, swollen and painful lymph nodes, and lumps; others will experience fever, headache, dizziness, fatigue, and general discomfort. These local or systemic inflammatory reactions are all nonspecific immune damage after vaccination.

This is because most traditional vaccines are made by inactivating, attenuating, and purifying pathogenic microorganisms or their sugar molecules and protein molecule subunits. Therefore, these vaccines themselves contain some inherent biological characteristics, such as toxicity, bacterial proteins and metabolites, which may induce nonspecific immune responses.

In addition, vaccine products, in addition to pathogenic microorganisms or their subunit components, also contain stabilizers, preservatives, adsorbents, etc. For the human body, these are all "foreign substances" and may cause nonspecific immune responses.

2. Specific immune damage

Since there are non-specific ones, there are also specific immune damages. Its scientific name is hypersensitivity reaction, also known as allergic reaction or allergic reaction.

Under normal circumstances, the human body's specific immune system can eliminate "foreign matter" after contact with it, while also maintaining a relatively stable internal environment. Hypersensitivity, as the name suggests, is an overreaction to foreign matter, resulting in physiological dysfunction or tissue cell damage. Hypersensitivity is usually a reaction caused by the body's initial response to an antigen and then being exposed to the same antigen again.

The specific pathogenesis of hypersensitivity reactions is relatively complex, and the clinical manifestations vary. In simple terms, hypersensitivity reactions may occur seconds, hours, days, or even weeks after vaccination, and may manifest as rashes, allergic rhinitis, urticaria, itching, etc. In severe cases, laryngeal edema, anaphylactic shock, and even death may occur.

Overreaction丨Image source: Weibo@假面猫耳

The first question is, hypersensitivity reaction is a reaction caused by "re-exposure to the same antigen", why do some people have hypersensitivity reaction after the first vaccination?

Indeed, if a person has not been exposed to a certain pathogen, he or she will basically not have a hypersensitivity reaction to the pathogen. Therefore, except for very rare special cases, the hypersensitivity reaction after the first vaccination is generally not related to the pathogenic microorganisms or their subunit components in the vaccine, but is caused by other components in the vaccine product. As mentioned above, vaccine products also contain stabilizers, adsorbents, preservatives, etc. What are the main components?

Culture medium: Some vaccines are prepared using eggs or chicken embryos as culture medium, so people who are allergic to eggs may experience hypersensitivity reactions after vaccination.

Gelatin: Gelatin is a volume expander and heat stabilizer for many vaccines. It is obtained by hydrolysis of animal collagen and comes from the skin, bones, tendons, etc. of cattle, pigs and other animals.

Thimerosal: Thimerosal is an organic compound containing ethylmercury that has been widely used as a preservative in vaccines since the 1930s.

Antibiotics: Some vaccines contain trace amounts of antibiotics, such as neomycin, streptomycin, polymyxin, etc.

Latex: Mainly found in the containers or syringes of vaccine products, latex contains plant protein and peptide impurities that can cause hypersensitivity reactions.

Adjuvant: Adjuvant refers to a non-specific immune enhancer that can bind to antigens and promote the action of antigens. Commonly used ones include aluminum salts, saponins (QS-21), muramic acid dipeptides/tripeptides, monophosphoryl lipid A, cytokines, etc. The adjuvant used in vaccine products is not necessarily a single ingredient, but can also be obtained by compounding multiple ingredients. (For more information, please read "The Wonderful Ingredients in Vaccines")

In addition to the traditional vaccines mentioned above, there are two new vaccines this year: mRNA vaccines and adenovirus vector vaccines.

Theoretically, mRNA itself does not cause specific immunity. So, besides mRNA, what other ingredients are there in the vaccine? According to the information submitted by Pfizer and BioNTech to the U.S. Food and Drug Administration (FDA), we know that this mRNA vaccine also includes lipid nanoparticles (LNP) (Note: carrier material that delivers mRNA into the human body) and some chemicals, including potassium chloride, potassium dihydrogen phosphate, sodium chloride, disodium hydrogen phosphate dihydrate and sucrose, and does not contain egg ingredients, preservatives, latex, etc. [1]

Comparison of the ingredients of the Pfizer-BioNTech and Moderna vaccines[2] (translation by the author)

The situation of adenovirus vector vaccines is more complicated. Adenovirus is a non-enveloped double-stranded DNA virus that can infect the respiratory tract, eyes, and gastrointestinal tract. Most people with normal immune function can recover after infection. Globally, a considerable proportion of the population already has adenovirus antibodies, which means they already have pre-existing immunity. Whether "pre-existing immunity" will affect the effectiveness of the vaccine is also a concern in the field.

However, adenovirus vectors are essentially "foreign substances" that can stimulate the human body to produce nonspecific/specific immune responses. On February 27, 2021, the U.S. FDA approved Johnson & Johnson's adenovirus vector COVID-19 vaccine. According to information released by the FDA, in addition to the vector, it includes citric acid monohydrate, sodium citrate dihydrate, ethanol, 2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, and sodium chloride. It also does not contain egg ingredients, preservatives, and latex [3]. On March 11, 2021, Johnson & Johnson's adenovirus vaccine was also approved in the European Union. There is less information on the other ingredients of CanSino's adenovirus COVID-19 vaccine.

The second question also arises. Some vaccines need to be administered multiple times (Note: including Sinovac's inactivated COVID-19 vaccine and Fosun's COVID-19 mRNA vaccine). If there are no obvious adverse reactions after the first injection, will there be adverse reactions after the second injection?

The answer is: It is possible!

Whether it is the pathogenic microorganisms or their components in the vaccine, or other ingredients in the vaccine, they may become allergens. Arthus reaction is a hypersensitivity reaction that may occur when the vaccine is repeatedly administered. When the same antigen is injected again, the antigen and antibody combine to form immune complexes. Neutrophils react with the immune complexes, releasing damaging substances and destroying surrounding tissues. If the immune complexes are deposited in the skin, it will cause redness, edema, and even necrosis of the skin.

This shows that the reaction after the second vaccination also needs attention!

Will there be any adverse reactions?

Severity of adverse reactions

It is also related to individual factors

Why do adverse reactions occur after vaccination? The reasons are very complicated. In addition to the vaccine product itself, it is also related to human physiological factors and health status.

If the vaccine is administered in poor health conditions, for example, the vaccine recipient has severe malnutrition, wasting disease, etc., adverse reactions are likely to occur.

Adverse reactions may be aggravated by strenuous exercise and heavy physical activity after vaccination.

Drinking alcohol and lack of sleep after vaccination may also aggravate adverse reactions.

People with immune abnormalities, such as those with immunodeficiency, HIV infection, organ or hematopoietic stem cell transplantation, those using immunosuppressants, etc., need to undergo a more detailed evaluation before vaccination.

Seeing this, you will find that there are many factors that may cause adverse reactions to vaccines. But in fact, different vaccine products contain different ingredients, and the types of ingredients contained in each vaccine are limited. The number of people who will be allergic to these ingredients is limited, so the proportion of adverse reactions is extremely low.

On the other hand, "it is nonsense to talk about toxicity without considering the dosage." The content of allergens in vaccines is generally very low. Only people who have strong reactions to these allergens may experience allergic symptoms after vaccination.

To fully understand the adverse reactions of vaccines

Monitoring is important!

Compared with other drugs, the society has higher requirements for vaccine safety monitoring. In the "Safety Monitoring of Immunization", the World Health Organization (WHO) defines "adverse event following immunization" (AEFI) as any adverse reaction that occurs after vaccination and is believed to be caused by vaccination.

AEFI may be a true adverse reaction, which is indeed the result of the vaccine or the immunization process; it may also be a coincidence, that is, it is not caused by the vaccine or the immunization process, but is only related to the immunization in terms of the event.

WHO classifies AEFI into five categories:

1. Vaccine reaction: an event caused by certain components of the vaccine (active ingredients of the vaccine itself, preservatives, stabilizers, etc.).

2. Implementation errors: events caused by errors in vaccine preparation, administration or vaccination process.

3. Coincidental event: an event that occurs after vaccination but is not caused by the vaccine or implementation.

4. Injection reaction: Anxiety about the injection itself, rather than events caused by the vaccine.

5. Unexplained reactions: events whose causes cannot be determined.

AEFI monitoring is the common responsibility of health departments, vaccine manufacturers, sales companies, disease control agencies and vaccination units in various countries. All countries have established their own AEFI reporting systems. Establishing and improving the AEFI monitoring system and collecting as much information as possible on adverse events that occur during the use of vaccines can effectively evaluate the safety of marketed vaccines and enhance the public's confidence in vaccination.

According to the different ways of identifying and reporting AEFI, AEFI monitoring can be divided into passive monitoring and active monitoring. Passive monitoring is the reporting of any adverse events suspected to be related to the vaccine by medical staff or the public; active monitoring is the systematic search for AEFI cases in the target population to obtain the occurrence and incidence of AEFI. The latter is mostly used in vaccine clinical research or special investigations.

In actual work, the two monitoring methods are used in combination. For example, my country has an acute flaccid paralysis monitoring system, which includes passive reports from medical staff when routine cases seek medical treatment due to symptoms, as well as active investigations conducted by disease control agency personnel at medical institutions on a regular basis.

my country officially implemented the "Vaccine Circulation and Vaccination Management Regulations" on June 1, 2005. After the "National Suspected Adverse Reactions to Vaccination Monitoring Program" (hereinafter referred to as the "Monitoring Program") was issued in 2010, China's AEFI monitoring work has become increasingly standardized. The classification of AEFI in my country's "Monitoring Program" is different from that of WHO:

1. Adverse reactions: Harmful reactions unrelated to the purpose of vaccination or unexpected reactions that occur after the qualified vaccine is administered in a standardized manner, including general reactions and abnormal reactions.

General reaction: occurs after vaccination, caused by the inherent characteristics of the vaccine itself, and only causes transient physiological dysfunction in the body without leaving any sequelae. (Note: mainly includes non-specific immune damage such as fever, fatigue, local redness and swelling, pain, etc.)

Abnormal reaction: A qualified vaccine, during or after the standardized vaccination, causes damage to the recipient's body tissues, organs, and functions, and is an adverse drug reaction that is not the fault of any of the parties involved. (Note: Hypersensitivity is the most common abnormal reaction)

2. Vaccine quality accidents: Due to substandard vaccine quality, vaccination causes damage to the recipient's body tissues, organs and functions.

3. Vaccination accidents: During the implementation of vaccination, violations of vaccination work specifications, immunization procedures, vaccine use guidelines, and vaccination plans result in damage to the recipient's body tissues, organs, and functions.

4. Psychogenic reaction: Individual or group reaction caused by psychological factors of the vaccine recipients during or after vaccination.

5. Coincidence: The recipient is in the incubation period or prodromal period of a certain disease at the time of vaccination, and the disease coincidentally occurs after vaccination.

From the above AEFI monitoring classification, we can see that, strictly speaking, there are many types of AEFI classification. In a narrow sense, AEFI mainly refers to the "vaccine reaction" in the WHO classification or the "adverse reaction" in my country's "Monitoring Program".

Globally, the US has a relatively complete vaccine monitoring system. The US began monitoring adverse events after the launch of vaccines in the 1960s. In 1990, the US Centers for Disease Control and Prevention (CDC) and the FDA jointly established the Vaccine Adverse Event Reporting System (VAERS), which is managed by the two departments.

https://vaers.hhs.gov

VAERS is a voluntary reporting system for post-marketing safety monitoring of vaccines. The reports it receives mainly come from: vaccine manufacturers, medical and health practitioners, national immunization programs, vaccine recipients (or their families/guardians), and other information sources. Reporter can download VAERS form reports directly from the official website, or call to obtain VAERS forms, or use a copy of the form. All data are collected in the VAERS database. Among them, the United States defines serious adverse events as: ① causing death, ② endangering life, ③ leading to hospitalization or prolonged hospitalization, or ④ causing permanent disability.

The monitoring of AEFI in my country is jointly undertaken by the national health authorities and drug regulatory authorities. Reports are managed on a local basis. When medical institutions, vaccination units, disease prevention and control institutions, adverse drug reaction monitoring institutions, vaccine manufacturers and other responsible reporting units and reporters discover AEFI, they shall promptly report to the county (district, city, banner, the same below) level Center for Disease Control and Prevention (CDC) in their location. The county-level CDC will report the AEFI case report card and questionnaire information online through the national AEFI information management system. Vaccination units with reporting conditions can directly enter the AEFI case report card information into the national AEFI information management system. my country's definition of severe AEFI is basically the same as that of the United States: it refers to AEFI that causes death, endangers life, causes permanent or significant disability or organ damage.

What is the incidence rate of adverse events from the new coronavirus vaccine?

Currently, among the COVID-19 vaccines approved in my country, the data for Fosun Pharma’s mRNA COVID-19 vaccine (Note: Pfizer/BioNTech’s BNT162b2 mRNA vaccine) is relatively complete. In November 2020, the New England Journal of Medicine published the results of the Phase II/III clinical trial of the BNT162b2 mRNA vaccine [4].

The trial ultimately enrolled 43,448 subjects aged ≥16 years, who were divided into the mRNA vaccine group (21,720 subjects) and the placebo group (21,728 subjects) at a 1:1 ratio. The evaluation data of local and systemic reactions are as follows:

It can be seen that the most common local adverse reaction after vaccination is pain at the injection site, while systemic reactions are often fatigue and headache (Note: both of which are nonspecific immune reactions). The incidence of reactions in older people is lower than that in younger people. Local reactions are mostly mild to moderate and improve in 1 to 2 days. In terms of systemic reactions, 0.2% of patients developed high fever (38.9℃~40℃) after the first shot, 0.8% of patients developed high fever after the second shot, and 2 patients had a fever of more than 40℃. Fever and chills often occur within 1 to 2 days after vaccination, and the symptoms can be relieved in a short period of time.

All subjects were monitored for adverse events. In the vaccination group, 27% of the subjects reported adverse events (of any form), most of which were short-term local or systemic reactions after vaccination. Lymphadenopathy was reported in 64 (0.3%) vaccine group subjects; 4 serious adverse events occurred in the vaccine group (vaccine-related shoulder injury, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, right lower limb paresthesia), and 2 subjects died. After investigation, the researchers said that it was not related to the vaccination.

As the number of people receiving mRNA vaccines increases, relevant data is becoming more and more complete. The US CDC has also developed an APP to help with post-vaccination monitoring (v-safe).

On January 27, 2021, the U.S. CDC released the latest COVID-19 vaccine safety monitoring data from VAERS[5]. Some of the data are as follows:

According to VAERS data, for every million injections of the mRNA COVID-19 vaccine, there are approximately 372 non-serious allergic events (0.0372%). Combining the local and systemic reaction data above, we can see that they are much lower than the results of clinical trials. This situation is largely related to the "passive monitoring" method. For example, if mild, short-term local pain or fatigue occurs after vaccination, it will get better after rest. At this time, some vaccine recipients will not report it. Therefore, the estimation of the incidence of adverse events is more accurate based on clinical trial or special survey data, which are all conducted under the close observation of researchers and are "active monitoring." VAERS also encourages doctors and other vaccine-related personnel to report adverse events to obtain more reliable data.

On February 16, 2021, the Nature website published an article[6] discussing issues related to adverse reactions to the COVID-19 vaccine. How much do we know about rare but serious allergic reactions?

According to VAERS data, Moderna mRNA vaccine can cause 3 serious allergic events per million doses (0.0003%), Pfizer/BioNTech mRNA vaccine can cause 5 serious allergic events per million doses (0.0005%), and for the Oxford-AstraZeneca vaccine (adenovirus vector vaccine), 30 cases of severe allergic reactions have been confirmed in more than 3 million vaccinations to date.

In the past two days, Denmark reported that some people who received the Oxford-AstraZeneca adenovirus COVID-19 vaccine had serious thrombosis events. Many countries have suspended the vaccination of this vaccine, which has aroused concerns from all walks of life. For this reason, on March 11, the European Medicines Agency (EMA) stated that there is currently no evidence that thrombosis events are related to vaccination, and the number of thrombosis events in the vaccinated population is no higher than that in the general population. The EMA Pharmacovigilance Risk Assessment Committee (PRAC) has been reviewing the adverse events of thrombosis in the AstraZeneca vaccine, but also stated that because the benefits of the vaccine outweigh the risks, the vaccine can still be used during the investigation of thrombosis events. [7]

The specific reason why these vaccines cause allergic reactions is still unclear, and the National Institute of Allergy and Infectious Diseases (NIAID) has designed a clinical trial to identify potential causes. Researchers suspect that polyethylene glycol (PEG) contained in lipid nanoparticles (LNP) may be the substance that causes allergic reactions. There are currently no deaths directly attributed to the new crown vaccine.

Is the incidence of serious adverse events high?

That needs to be compared with the vaccines commonly used in the past!

First, let us look at the incidence of serious adverse events of several commonly used vaccines in China[8].

Results of AEFI classification reports of different vaccines in China in 2016 (partial)

Note: The original table is based on the unit of every 100,000 cases. In order to be consistent with the data of other studies and facilitate reading, it is changed here to the unit of every million cases.

According to the analysis of China's suspected adverse reactions to vaccination monitoring data in 2016, the total reported incidence of AEFI was 3.901/million cases (including general reactions and abnormal reactions, 0.03901%), of which the incidence of severe AEFI was 1.6/million cases (0.00016%).

Let’s look at data from a global study[9].

A total of 33 cases of severe allergic reactions (Note: The definition of severe allergic reactions in this study refers to acute, systemic, multi-organ system involvement, and potentially fatal allergic reactions) were confirmed in 25,173,965 vaccinations between 2009 and 2011, with an incidence of approximately 1.31 per million vaccinations (0.00013%). The data are as follows:

The incidence of severe hypersensitivity reactions to several commonly used vaccines worldwide (partial)

As mentioned above, according to VAERS test data, the incidence rate of serious adverse events for injection of mRNA COVID-19 vaccines is 0.0003%~0.0005%. Therefore, the incidence rate of serious adverse events for mRNA vaccines is higher than the overall level of previously commonly used vaccines.

However, the incidence of severe AEFI varies among different vaccines, and mRNA vaccines have not exceeded the high values ​​of previous single vaccines. Of course, due to the short application time of mRNA vaccines, its long-term safety and other unanswered questions will need to undergo longer tests.

Compared with mRNA vaccines, there are fewer large sample sizes and fully published data for recombinant adenovirus vector vaccines and inactivated vaccines. Here we share two officially published data. In August 2020, the results of the Phase II clinical trial of the recombinant adenovirus vector COVID-19 vaccine were published in The Lancet [10]. A total of 508 volunteers who met the requirements were included, of which 253 received a high-dose vaccine (1×10^11 virus particles), 129 received a low-dose vaccine (5×10^10 virus particles), and 126 received a placebo. The main results of the adverse event assessment are as follows:

Note: No serious adverse events were found.

The results of the Phase I/II clinical trial of Sinovac's inactivated COVID-19 vaccine were published in The Lancet Infection in February 2021 [11]. The trial included healthy volunteers aged ≥60 years, with an observation period of 28 days. The patients were given three different vaccination doses: 1.5 μg, 3 μg, and 6 μg. The safety results showed that the incidence of any adverse events in each group was:

All adverse events were mild to moderate. Injection site pain was the most common symptom, with an incidence of 9% (39/421 participants), and fever occurred in 3% (14/421 participants). No serious vaccine-related adverse events were observed.

The incidence of severe allergic reactions is extremely low

There seem to be many general reactions.

What should I do if adverse reactions occur?

1. General reaction

1. Local reactions, including pain, redness and swelling at the injection site, usually occur 12 to 24 hours after the injection of the vaccine. The range of redness and swelling is generally not large. Only a few people have redness and swelling > 5 cm in diameter. This situation generally subsides gradually within 24 to 48 hours. Mild local reactions do not require treatment. In the early stage of redness and swelling, local cold compresses can be used to reduce tissue congestion.

2. Systemic reactions, including fever and fatigue, generally last for 1 to 2 days. A few patients may also experience gastrointestinal symptoms such as nausea, vomiting, and diarrhea. These symptoms are usually more common on the day of vaccination and rarely last for 2 to 3 days. After a mild systemic reaction occurs, observe closely. Generally, no special treatment is required. Take adequate rest, drink plenty of water, and keep warm. For patients with severe symptoms, antipyretics and other drugs can be used according to the situation, and patients can be sent to the hospital for observation and treatment if necessary.

2. Abnormal reactions (mainly allergic reactions)

1. For those with mild symptoms, observation is sufficient and no medication is needed. If itching, skin flushing, urticaria, etc. occur, the doctor will give the patient oral antihistamines, H2 receptor antagonists, glucocorticoids and other treatments according to the situation; if symptoms of bronchospasm occur, such as chest tightness, shortness of breath, etc., short-acting β2 receptor agonists can be inhaled, and the emergency center should be contacted for further observation and treatment. In addition to the above symptoms, eczema, edema, purpura, etc. may also occur. Generally, there are no obvious acute discomfort symptoms, and no emergency measures are required. Patients can be arranged to see a corresponding specialist according to the situation.

2. Acute and severe allergic reaction, i.e. anaphylactic shock: It is extremely rare, but once it occurs, it can be life-threatening. The main symptoms are low blood pressure, sweating, pale skin, difficulty breathing, syncope, unconsciousness, etc. It develops very quickly and can occur within a few minutes after vaccination, usually within 30 minutes, and rarely more than 1 hour. This is why it is required to stay for at least 30 minutes after vaccination.

If anaphylactic shock occurs, epinephrine is the top priority drug for emergency treatment, and the airway and breathing must be maintained, and infusion monitoring is required. The emergency medical support capacity of some vaccination sites is limited, and patients must be transferred to emergency medical centers for continued treatment while emergency rescue is guaranteed.

3. Other more serious allergic reactions are very rare. For example, allergic purpura, Arthus reaction, Guillain-Barré syndrome, cerebrospinal meningitis, etc., can occur a few days or weeks after vaccination. Once the disease occurs, it is necessary to go to the corresponding specialist for evaluation and treatment.

Vaccines play a vital role in the fight between humans and diseases, and are universally recognized as the most economical, convenient, and effective means of preventing and controlling infectious diseases. However, no vaccine can achieve absolute safety (just like there is no absolute freedom in the world).

Since the vaccine is mainly administered to healthy people, the public's ability to bear risks is relatively weak, and people have higher requirements for vaccine safety. Many times, fear and distrust of a thing largely comes from "not understanding". Therefore, it is important to make everyone understand the mechanism of action of the vaccine as much as possible, publish relevant data on vaccination as much as possible, and let everyone know that the benefits of the vaccine far outweigh the risks. This is the key to enhancing confidence in immunization. Of course, we still have many questions that need time to answer in the evaluation of the safety of new vaccines. Overall, vaccines are the "angels" of the vast majority of people.

References

[1] https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Pfizer-BioNTech.html

[2] https://blog.jonasneubert.com/2021/01/10/exploring-the-supply-chain-of-the-pfizer-biontech-and-moderna-covid-19-vaccines/

[3] https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html

[4] Fernando P Polack, Stephen J Thomas, Nicholas Kitchin, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615.

[5] https://www.cdc.gov/vaccines/acip/meetings/slides-2021-1-27-21.html

[6] https://www.nature.com/articles/d41586-021-00290-x

[7] https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-prac-investigating-cases-thromboembolic-events-vaccines-benefits

[8] Xu Disha, Li Keli, Wu Wendi, et al. Analysis of surveillance data on suspected adverse reactions to vaccination in China in 2016. Chinese Journal of Vaccines and Immunization. 2018;24(3):299-322.

[9] McNeil MM, Weintraub ES, Duffy J, et al. Risk of anaphylaxis after vaccination in children and adults. J Allergy Clin Immunol 2016;137:868–78.

[10] Feng-Cai Zhu, Xu-Hua Guan, Yu-Hua Li, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomized, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;396(10249):479-488.

[11] Zhiwei Wu, Yaling Hu, Miao Xu, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomized, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;S1473-3099(20)30987-7.