New England Journal of Medicine review: Safety of the new crown vaccine

Millions or even billions of people around the world will be vaccinated against the new crown vaccine in the coming months, and several cases of severe allergic reactions following mass vaccinations of the mRNA vaccine have caused serious public concern.
to ensure the maximum effectiveness and safety of vaccines, is the world's top priority after the issuance of emergency vaccine authorization.
Last Wednesday (December 30, 2020), the New England Journal of Medicine (NEJM) published a review of "Ensuring the Safety of the SARS-Cov-2 Vaccine", detailing the most likely allergens and their allergenic mechanisms associated with the mRNA vaccine, public health and individual responses, and questions that remain to be answered.
review was written by two immunologists from Harvard Medical School and Vanderbilt University Medical Center who specialize in drug allergies.
call for long-term, systematic monitoring of vaccine-related adverse events, they also point out that vaccine-related "severe allergic reactions can be cured without permanent damage" (Anaphylaxis is treatable with no permanent effects).
guarantee the safety of the SARS-Cov-2 vaccine Maintaining Safety with SARS-CoV-2 Vaccines Castells MC, Phillips EJ DOI: 10.1056/NEJMra2035343 To date, the development of an mRNA vaccine to prevent SARS-CoV-2 infection has been successful and has not been seriously affected during the ongoing Phase 3 clinical trials.
mild local side effects such as pain, redness and swelling were higher in the vaccine group than in the placebo group.
of systemic symptoms such as fever, fatigue, headache, muscle and joint pain were also slightly higher in the vaccine group than in the placebo group, and most of the symptoms occurred within 24 to 48 hours of vaccination.
mRNA vaccine, developed in a joint Pfizer-BioNTech and developed by Moderna, excluded potential participants with a history of allergies to any of the vaccine's components in Phase 1-3 clinical trials.
's vaccine study at Pfizer-BioNTech also excluded participants with a history of severe allergies to any vaccine (the full exclusion criteria can be found in both trials, which are available in full on NEJM.org).
in both trials, placebo (normal physiological saline) and vaccine groups had the same rate of allergic adverse events.
the UK Medicines and Healthcare Products Regulatory Agency (MHRA) earlier granted emergency approval for the Pfizer-BioNTech mRNA vaccine.
On 8 December 2020, two suspected cases of severe allergic reactions were reported in the UK within 24 hours of the launch of the mass vaccination programme for health care workers and the elderly: women aged 40 and 49, both with a known history of allergies to food and medicine, and carrying epinephrine auto-injectors with them.
On December 11, the U.S. Food and Drug Administration (FDA) granted Pfizer-BioNTech mRNA vaccine emergency use authorization (EUA) and began universal vaccination of health care workers on Monday, December 14.
December 15, an Alaskan vaccinator with a known history of allergies developed a severe allergic reaction within 10 minutes of the first dose of the vaccine.
the three earliest reported severe allergic reactions, the researchers would not rule them out based on their medical history if the participants who had these reactions were initially involved in clinical trials of the mRNA vaccine.
first severe allergic reaction in Alaska, nearly 2 million U.S. health care workers have reported several serious allergic reactions associated with the vaccine after being vaccinated against Pfizer mRNA.
The rate of severe allergic reactions associated with the Pfizer SARS-CoV-2 mRNA vaccine appears to be about 10 times higher than previously reported in various vaccines, the former being about one in 100,000 and the latter about one in a million (the known stable rate of severe allergic reactions associated with other vaccines). the
ModnamRNA vaccine, issued on December 18th, is too early to say whether the vaccine will have a similar severe allergic reaction, but a small number of suspicious cases of severe allergic reactions have been reported, including a severe allergic reaction on December 24th by a Boston health care worker who was allergic to shellfish food and carried an epinephrine auto-injector.
MHRA suspended the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine for anyone with a history of severe allergic reactions to any food, drug or vaccine in response to two severe allergic reactions in the UK.
The U.S. Centers for Disease Control and Prevention (CDC) has issued recommendations for the first or second dose of the Pfizer-BioNTech or ModnamRNA vaccine, recommending that no one with a history of severe or rapid hair allergic reactions (within 4 hours) of any vaccine ingredient, including PEG derivatives such as polyethyl glycol (PEG) and polysorbite, be vaccinated against such vaccines.
severe allergic reaction is a severe multi-system reaction that starts quickly and can lead to death due to asphyxia, cardiovascular failure and other complications.
need to be diagnosed quickly and given epinephrine treatment to block the rapid progress of life-threatening symptoms.
The mechanism of severe allergic reactions is that antigens bind to IgE and cross-link to activate fat cells, which release inflammatory media such as histamines, proteases, prostaglandins, and triene, causing tissue reactions that produce symptoms such as redness, urticaria, throat edema, wheeping, nausea, vomiting, tachyrosis, hypotension, and cardiovascular failure.
patients who had been exposed to antigens became IgE-sensitive.
previously known as allergic reactions, reactions with similar symptoms and signs to severe allergic reactions are now known as non-IgE-mediated reactions because they are found not to involve IgE.
the same clinical manifestations as severe allergic reactions and the same response to epinephrine.
but its mechanism is to activate fat cells and alkaline granulocytes directly, complement activation, or other pathways, and can occur when exposed to antigens for the first time.
blood trypsin levels usually increase when severe allergic reactions mediated by IgE and non-IgE-mediated hypertrophic cell activation (small increases) occur, a characteristic that determines that fat cells are the source of inflammatory media.
skin pointing experiments and in-skin experiments, as well as serum IgE testing, can be used to determine the specific drugs that cause the reaction, but the negative predicted value of these tests is not 100%.
two cases in the UK and one case in the US are clinically consistent with severe allergic reactions: within minutes of injection, symptoms are typical, and epinephrine therapy is effective.
reactions that occur during initial exposure are not typical IgE-mediated reactions; however, pre-sensitivity to an ingredient in the vaccine may be the cause of this result.
severe allergic reactions can be cured without permanent damage.
, however, news of these adverse reactions has raised concerns about the risks of new vaccines.
These cases of severe allergic reactions raise more questions than answers; however, such safety signals are almost inevitable when vaccination programmes involving millions of people are launched; they highlight the need for a firm, proactive "safety roadmap" to identify pathogenesis, identify people at risk of such reactions, and adopt strategies that contribute to treatment and prevention (Figure 1).
. The evaluation of the SARS-CoV-2 mRNA vaccine for vaccine response is based on the same lipid nanoparticle-carrying technology;
Operation Warp Speed has enabled us to respond at an unprecedented rate, conduct safety and effective studies of new vaccines that have never been used in humans, and have developed and approved vaccines less than a year after the SARS-CoV-2 virus sequence was identified.
several such vaccines are likely to be approved in the coming months, and inevitably adverse events that have not been observed in the clinical trials required to obtain EUA.
ensuring vaccine safety requires proactive action to ensure public confidence and reduce hesitation about vaccination.
these measures include not only vigilance and careful response, documentation of adverse events and clarity of their characteristics in order to identify and clarify their mechanisms, but also appropriate methods for predicting, preventing and treating adverse events.
first step in adopting a systematic approach to adverse vaccine reactions is clinical diagnosis and appropriate initial treatment, followed by a detailed inquiry of the medical history and a causal assessment.
Non-immune-mediated rapid reactions (e.g., vasculation neuroreacts) are more common, generally manifested as sweating, nausea, vomiting, paleness, and tachyheia;
clinical evaluation of vaccine reactions should be done by allergy-immunologists, including skin trials of vaccine ingredients, which may be beneficial.
results of other laboratory tests may contribute to clinical and institutional assessments and guide future vaccine and drug safety assessments and treatments, such as the use of other vaccines for excitation trials when revaccination is required.
can search for information on drugs and vaccines is: .
information on the agents of approved vaccines is: https://we can rest assured that for most known vaccines, vaccine-related severe allergic reactions are extremely rare, with a rate of only one in a million.
allergic reactions after vaccination may be caused by vaccine antigens, residual non-human proteins, or preservatives and stabilizers (also known as emoticons) in vaccine formulations.
While local reactions may be mostly related to active antigens in vaccines, IgE-mediated reactions or severe allergic reactions have traditionally been more associated with inactive ingredients or substances in the vaccine production process, such as eggs, gelatin or latex.
mRNA vaccines developed by Pfizer-BioNtech and Modena use lipid nanoparticle carrier systems to prevent mRNA from being rapidly degraded by enzymes and facilitate in vivo delivery of vaccines.
this lipid nanoparticle-carrying drug system is combined with polyethyl glycol (PEG) 2000 lipid conjugate, peG lipids further enhance the stability of the drug-carrying system and provide it with a hydrophobic layer to extend the half-life.
mRNA vaccine is not a new technology, there is currently no licensed mRNA vaccine.
Pfizer-BioNtech and Modner are the first two mRNA vaccines to be obtained from EUA.
, we do not have any experience with the likely occurrence or mechanism of allergic reactions associated with the mRNA vaccine.
this may be the case: some populations have a higher risk of non-IgE-mediated activation of fat cells or complement activation, which is associated with vaccine lipids or PEG lipid components.
As a comparison, up to 40% of patients will have an infusion reaction after entering preparations such as polyethyl glycol liposome polyjust, and it is currently assumed that the infusion reaction occurs because the patient activates the supplement after the first injection of the drug without contact with the drug, and the reaction can be reduced after the second and subsequent injection of such drugs.
, PEG is considered a rare "hidden danger" for IgE-mediated reactions and relapses of severe allergic reactions.
mRNA vaccine contains lipid PEG 2000, there are concerns that the ingredient may be associated with severe allergic reactions.
, no other vaccines with PEG as an agent have been widely used.
the risk of allergenicity from drugs containing high molecular weight PEG injections appears to be higher, and cases of severe allergic reactions have been reported after intestinal preparation with drugs containing PEG 3350 to PEG 4000.
case reports included a patient who developed a severe allergic reaction after receiving preparation with PEG 3350, after which the patient was first exposed to polyethyl glycol lipid microfoules (i.e., PEGLip 5000 perfluoropropanane ultrasonic heartbeat graph agent (Definity)) and a warning of a rapid hair-sensitive reaction on the label.
it appears that FOR drugs containing PEG 3350, such as methadone acetate and methicillin for injection, PEG ingredients are more likely to cause severe allergic reactions than active drugs.
patients with a history of severe allergic reactions to Pfizer-BioNTech's SARS-CoV-2 mRNA vaccine are at risk of developing severe allergic reactions if they are revaccinated against Modner's SARS-CoV-2 mRNA vaccine, which also uses a PEG 2000-based delivery system, but the lipid mixture is different (see Table 1).
Table 1. The SARS-CoV-2 vaccine, constructed in adenovirus vectors and protein sub-units by obtaining authorization for emergency use (EUA) or at a later stage of research, typically uses polysorbide 80 (an ionic surfactant and emulsion similar in structure similar to PEG) as an extrusion agent, and its future application is currently unknown.
In accordance with the current recommendation of the CDC in the United States, no one with a history of severe allergic reactions to any component of the SARS-Cov-2 mRNA vaccine should be vaccinated against such vaccines, and the current recommendation also requires that no one with a history of PEG-related rapid reactions be vaccinated against such vaccines.
addition, the recommendation requires patients with severe allergic reactions after being vaccinated against BioNTech-Pfizer or Modner to avoid a variety of m-based PEG 2000 as an exoneration