Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines

Authors: Johanna Chapin-Bardales, PhD, MPH1Julianne Gee, MPH1Tanya Myers, PhD, MSc1

In December 2020, 2 mRNA-based COVID-19 vaccines (Pfizer-BioNTech and Moderna) were granted Emergency Use Authorization by the US Food and Drug Administration as 2-dose series and recommended for use by the Advisory Committee on Immunization Practices.13 In late February 2021, the US Food and Drug Administration granted Emergency Use Authorization for a third COVID-19 vaccine, a single-dose adenovirus vector-based vaccine from Janssen (Johnson & Johnson).

In clinical trials of the mRNA-based 2-dose vaccines, participants reported local and systemic reactions (reactogenicity).4,5 Frequently reported reactions included injection site pain, fatigue, and headache; greater reactogenicity was reported following the second dose.4,5 Continued monitoring of reactogenicity of COVID-19 vaccines outside of clinical trial settings may provide additional information for health care practitioners and the public about transient local and systemic reactions following COVID-19 vaccination.

V-safe Active Surveillance System

To facilitate rapid assessment of COVID-19 vaccines, in 2020, the Centers for Disease Control and Prevention (CDC) established v-safe, a new active surveillance system for collecting near–real-time data from COVID-19 vaccine recipients in the US. V-safe participants voluntarily self-enroll and receive periodic smartphone text messages to initiate web-based health surveys from the day of vaccination (day 0) through 12 months after the final dose of a COVID-19 vaccine.6 From day 0 through day 7 after each vaccine dose, participants are asked questions about solicited local and systemic reactions (eg, injection site pain, fatigue, headache). These solicited reactions do not include allergic reactions or anaphylaxis; however, v-safe does allow participants to enter free-text information about their postvaccination experience and asks about adverse health events (eg, received medical care). Medically attended events are followed up on through active telephone outreach; future analyses will address these adverse vaccine experiences. This report describes information on solicited local and systemic reactogenicity reported to v-safe on days 0 to 7 after each dose of vaccine from December 14, 2020, through February 28, 2021. Responses were limited to individuals who were vaccinated by February 21, 2021, to allow a 7-day reporting period after the day of vaccination. Preliminary data from v-safe through January 13, 2021, have been previously reported.7 This activity was reviewed by the CDC and was conducted consistent with applicable federal law and CDC policy (see Additional Information).

Self-reported Local and Systemic Reactions Among V-safe Participants

By February 21, 2021, more than 46 million persons received at least 1 dose of an mRNA-based COVID-19 vaccine.8 A total of 3 643 918 persons were enrolled in v-safe and completed at least 1 health survey within 7 days following their first vaccine dose; 1 920 872 v-safe participants reported receiving a second vaccine dose and completed at least 1 daily health survey within 7 days following the second dose. Solicited local and systemic reactions during days 0 to 7 after each dose were assessed.

Most v-safe participants reported an injection site reaction (dose 1: 70.0%; dose 2: 75.2%) or a systemic reaction (dose 1: 50.0%; dose 2: 69.4%) during days 0 to 7 after vaccination (Table). The most frequently reported solicited local and systemic reactions after the first dose of COVID-19 vaccine were injection site pain (67.8%), fatigue (30.9%), headache (25.9%), and myalgia (19.4%). Reactogenicity was substantially greater after the second dose for both vaccines, particularly for systemic reactions, including fatigue (53.9%), headache (46.7%), myalgia (44.0%), chills (31.3%), fever (29.5%), and joint pain (25.6%).Table.  Solicited Local and Systemic Reactionsa to mRNA-Based COVID-19 Vaccines Reported 0 to 7 Days After Vaccination—Centers for Disease Control and Prevention V-safe Surveillance System, December 14, 2020, to February 28, 2021 View LargeDownload

Solicited Local and Systemic Reactionsa to mRNA-Based COVID-19 Vaccines Reported 0 to 7 Days After Vaccination—Centers for Disease Control and Prevention V-safe Surveillance System, December 14, 2020, to February 28, 2021

A greater percentage of participants who received the Moderna vaccine, compared with the Pfizer-BioNTech vaccine, reported reactogenicity; this pattern was more pronounced after the second dose (Table). When stratified by age (<65 vs ≥65 years), differences in reactogenicity by vaccine remained consistent with overall findings (data not shown). Local and systemic reactions were less commonly reported by v-safe participants 65 years and older compared with those younger than 65 years, but greater reactogenicity after the second dose was observed for both age groups (eFigure in the Supplement). For both doses of both vaccines, the percentage of v-safe participants who reported local and systemic reactions was highest on day 1 after vaccination and declined markedly through day 7.

For More Information: https://jamanetwork.com/journals/jama/fullarticle/2778441

Scientists explain possible causes of anaphylaxis following mRNA COVID-19 vaccination

Authors: By Angela Betsaida B. Laguipo, BSN

In an effort to stem the spread of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, vaccination efforts have been implemented in most countries.

Two of the vaccines developed to prevent SARS-CoV-2 infection are the novel messenger ribonucleic acid (mRNA) vaccines: the Pfizer-BioNTech (BNT162b2) and the Moderna (mRNA-1273) vaccines.

Despite this vaccine type’s novelty, mRNA vaccines have been studied by scientists for decades. Moreover, both vaccines underwent extensive testing and rigorous clinical trials to determine their safety and efficacy.

Against the backdrop of a global public health emergency, clinical trials and regulatory body approval for both mRNA vaccines had been compressed into a shorter timespan than usual for novel pharmaceuticals like these. However, no safety measures had been compromised in the process, and all of the usual protocols were still followed within this expedited timeframe.

The pharmaceutical companies made this possible by conducting overlapping clinical trials, which involve human testing and occur in three phases that scale up each time. Meanwhile, some regulatory bodies – like the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK –  conducted a ‘rolling review’ of the trial data for both vaccines as and when it was made available. This is an emergency measure that is employed to speed up the process in pressing instances like global pandemics.

This said, as with all pharmaceuticals, a small subset of individuals are unfortunately susceptible to adverse reactions, something which is not always detected at the clinical trial level. This includes, though is not limited to, anaphylaxis or allergic reactions to ingredients that vaccines sometimes contain or are stored in.

A new report from a team of scientists at the Centre for Research in Molecular Modeling, Department of Chemistry and Biochemistry, Concordia University in Canada, has aimed to determine the potential causes of anaphylaxis or allergic reactions reported in some individuals after receiving COVID-19 vaccines, including the mRNA vaccines by Pfizer-BioNTech and Moderna.

For More Information: https://www.news-medical.net/news/20210601/Scientists-explain-possible-causes-of-anaphylaxis-following-mRNA-COVID-19-vaccination.aspx

Anaphylaxis is a rare reaction in COVID-19 vaccination

Authors: R G Bellomo 1C E Gallenga 2Al Caraffa 3G Tetè 4G Ronconi 5P Conti 6

Abstract

Anaphylaxis is a severe multisystem reaction that occurs rapidly after the introduction of an antigen that would otherwise be a harmless substance. It is characterized by airway and respiratory problems, cardiovascular collapse, mucosal inflammation, and other complications, all severe symptoms that can cause death. IgE-dependent anaphylaxis involves mast cells (MCs) which are the main sources of biologically active mediators that contribute to the pathological and lethal phenomena that can occur in anaphylaxis. Antibody-mediated anaphylaxis can follow multiple pathways such as that mediated by MCs carrying the FcεRI receptor, which can be activated by very small amounts of antigen including a vaccine antigen and trigger an anaphylactic reaction. In addition, anaphylaxis can also be provoked by high concentrations of IgG antibodies that bind to the FcγR receptor present on basophils, neutrophils, macrophages and MCs. For this reason, the IgG concentration should be kept under control in vaccinations. Activation of MCs is a major cause of anaphylaxis, which requires immediate treatment with epinephrine to arrest severe lethal symptoms. MCs are activated through the antigen binding and cross-linking of IgE with release of mediators such as histamine, proteases, prostaglandins, leukotrienes and inflammatory cytokines. The release of these compounds causes nausea, vomiting, hives, wheezing, flushing, tachycardia, hypotension, laryngeal edema, and cardiovascular collapse. mRNA and viral vector vaccines have been cleared by the United States, Food and Drug Administration (FDA), generating hope of prevention and cure for COVID-19 around the world. Scientists advise against giving the vaccine to individuals who have had a previous history of anaphylaxis. The US Centers for Disease Control and Prevention (CDC) advises people with a previous history of any immediate allergic reaction to remain under observation for approximately 30 minutes after COVID-19 vaccination. To date, vaccines that prevent SARS-CoV-2 infection have not raised major concerns of severe allergic reactions, although, in some cases, pain and redness at the injection site and fever have occurred after administration of the vaccine. These reactions occur in the first 24-48 hours after vaccination. It has been reported that probable forms of anaphylaxis could also occur, especially in women approximately 40 years of age. But after tens of millions of vaccinations, only a few patients had this severe reaction with a low incidence. Anaphylactic and severe allergic reactions can also occur to any component of the vaccine including polysorbates and polyethylene glycol. To date, there is no precise information on allergic reactions to COVID-19 vaccines. Individuals with MCs and complement with higher activation than others may be at greater allergic risk. Moreover, the reactions called anaphylactoids, are those not mediated by IgE because they do not involve this antibody and can also occur in COVID-19 vaccination. These not-IgE-mediated reactions occur through direct activation of MCs and complement with tryptase production, but to a lesser extent than IgE-mediated anaphylaxis. However, at the moment it is not known exactly which component of the vaccine causes the allergic reaction and which vaccine causes the most side effects, including anaphylaxis. Thus, individuals who have a known allergy to any component of the vaccine should not be vaccinated. However, should an anaphylactic reaction occur, this requires immediate treatment with epinephrine to arrest severe lethal symptoms. In conclusion, the purpose of this editorial is to encourage the population to be vaccinated in order to extinguish this global pandemic that is afflicting the world population, and to reassure individuals that anaphylactic reactions do not occur with a higher incidence than other vaccinations.

For More Information: https://pubmed.ncbi.nlm.nih.gov/34105336/

Interim Considerations: Preparing for the Potential Management of Anaphylaxis after COVID-19 Vaccination

Authors: CDC

Summary of recent changes (last updated March 3, 2021)

  • Considerations broadened to include use of Janssen (Johnson & Johnson) COVID-19 vaccine.

Key Points

Under the Emergency Use Authorizationsexternal icon for COVID-19 vaccines, appropriate medical treatment for severe allergic reactions must be immediately available in the event that an acute anaphylactic reaction occurs following administration of a COVID-19 vaccine. These interim considerations provide information on preparing for the initial assessment and management of anaphylaxis following COVID-19 vaccination.

Overview

Anaphylaxis, an acute and potentially life-threatening allergic reaction, has been reported rarely following COVID-19 vaccination. These interim considerations provide recommendations on assessment and management of anaphylaxis following COVID-19 vaccination. Detailed information on CDC recommendations for vaccination, including contraindications and precautions to vaccination, can be found in the Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. Patients should be screened prior to receipt of each vaccine dose, and those with a contraindication should not be vaccinated. A COVID-19 prevaccination questionnaire pdf icon[6 pages] is available to assist with screening.

For More Information: https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html

Biden team’s misguided and deadly COVID-19 vaccine strategy

Vaccination ‘arms race’ could prove dangerous to the American public

Authors: Dr. Robert Malone and Peter Navarro

The Biden administration’s strategy to universally vaccinate in the middle of the pandemic is bad science and badly needs a reboot.

This strategy will likely prolong the most dangerous phase of the worst pandemic since 1918 and almost assuredly cause more harm than good – even as it undermines faith in the entire public health system.

Four flawed assumptions drive the Biden strategy. The first is that universal vaccination can eradicate the virus and secure economic recovery by achieving herd immunity throughout the country (and the world).  However, the virus is now so deeply embedded in the world population that, unlike polio and smallpox, eradication is unachievable. SARS-CoV-2 and its myriad mutations will likely continually circulate, much like the common cold and influenza.

The second assumption is that the vaccines are (near) perfectly effective. However, our currently available vaccines are quite “leaky.” While good at preventing severe disease and death, they only reduce, not eliminate, the risk of infection, replication, and transmission. As a slide deck from the Centers for Disease Control has revealed, even 100% acceptance of the current leaky vaccines combined with strict mask compliance will not stop the highly contagious Delta variant from spreading.

The third assumption is that the vaccines are safe.  Yet scientists, physicians, and public health officials now recognize risks that are rare but by no means trivial.  Known side effects include serious cardiac and thrombotic conditions, menstrual cycle disruptions, Bell’s Palsy, Guillain Barre syndrome, and anaphylaxis.

Unknown side effects which virologists fear may emerge include existential reproductive risks, additional autoimmune conditions, and various forms of disease enhancement, i.e., the vaccines can make people more vulnerable to reinfection by SARS-CoV-2 or reactivation of latent viral infections and associated diseases such as shingles.  With good reason, the FDA has yet to approve the vaccines now administered under Emergency Use Authorization.

The failure of the fourth “durability” assumption is the most alarming and perplexing.  It now appears our current vaccines are likely to offer a mere 180-day window of protection – a decided lack of durability underscored by scientific evidence from Israel and confirmed by  Pfizer, the Department of Health and Human Services, and other countries. 

For More Information: https://www.washingtontimes.com/news/2021/aug/5/biden-teams-misguided-and-deadly-covid-19-vaccine-/