ISOP ISRAEL - The Israeli Chapter of the International Society of Pharmacovigilance

THEORY 1-  The vaccines could cause illnesses.

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 20/01/2021 Ref: 0016 EN FALSE!

• No data suggests that vaccines could cause severe diseases. The vaccinated participants in the vaccine trials do not show a higher rate of severe illness compared to unvaccinated participants.
  
• The mRNA vaccines do not contain or induce the production of any pathogen substance; they do not contain any virus or any part of it and have been synthesized in laboratories or in manufacturing facilities where the virus has never been introduced.
  
• Post vaccinal follow-up is carefully monitored in order to detect the eventual occurrence of any uncommon side effect.

THEORY 2-  There are unwanted components in the vaccine

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 20/01/2021 Ref: 0013 EN FALSE! None of these unwanted components are present in the mRNA vaccines such as live viruses, inactivated viruses, gluten, egg proteins, pork products, foetal material, blood product, DNA, antibiotics, preservatives like thimerosal, adjuvants. The approval of the vaccines by Regulatory Health agencies like the FDA, the EMA etc. warrant their composition. __________________________ Sources: WHO:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines Health Feedback independent Professors:No evidence that COVID-19 vaccines cause more severe disease; antibody-dependent enhancement has not been observed in clinical trials
https://healthfeedback.org/claimreview/no-evidence-that-covid-19-vaccines-cause-more-severe-disease-antibody-dependent-enhancement-has-not-been-observed-in-clinical-trials/ Finnish Government:Vaccines and coronavirus
https://thl.fi/en/web/infectious-diseases-and-vaccinations/what-s-new/coronavirus-covid-19-latest-updates/transmission-and-protection-coronavirus/vaccines-and-coronavirus Hospital of Philadelphia:Questions and Answers about COVID-19 Vaccines
https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/prevent-covid?utm_source=prevent-covid&utm_medium=redirect&utm_campaign=VECCOVID

THEORY 3-  There is a connection between the 5G networks, the pandemics and the vaccines.

Vaccine Safety Net Resources Author: Task Force Vaccine ​​​​​​​Published: 20/01/2021 Ref: 0014 EN FALSE!

• There is absolutely no way that 5G mobile phone signals could either transmit the virus or reduce our defences to it.
  Viruses cannot travel on radio waves/mobile networks. In fact, COVID is spreading in many countries that do not have 5G.
  
• There is absolutely no connection between 5G networks and vaccines. Vaccines can’t be “activated “by 5G to harm people.

THEORY 4- Vaccines contain microchips that can track people

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 20/01/2021 Ref: 0015 EN FALSE !
The approval of the vaccines by Regulatory Health agencies like the FDA, the EMA etc. warrant their composition. _________________________ Sources: WHO:
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines Health Feedback independent Professors:No evidence that COVID-19 vaccines cause more severe disease; antibody-dependent enhancement has not been observed in clinical trials
https://healthfeedback.org/claimreview/no-evidence-that-covid-19-vaccines-cause-more-severe-disease-antibody-dependent-enhancement-has-not-been-observed-in-clinical-trials/ Finnish Government:Vaccines and coronavirus
https://thl.fi/en/web/infectious-diseases-and-vaccinations/what-s-new/coronavirus-covid-19-latest-updates/transmission-and-protection-coronavirus/vaccines-and-coronavirus Hospital of Philadelphia:Questions and Answers about COVID-19 Vaccines
https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/prevent-covid?utm_source=prevent-covid&utm_medium=redirect&utm_campaign=VECCOVID

THEORY 5- mRNA vaccines use a new technology and there has been no animal or clinical experimentation to test it.

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 21/01/2021 Ref: 0018 EN FALSE ! Research on mRNA vaccines began in the 1990s. Over the last ten years or so, numerous animal and human trials have been carried out, particularly during epidemics of two coronaviruses, SARS-CoV (2002-2003) and MERS-CoV (2012). A large amount of data has been collected and these data demonstrated the safety and efficacy of these mRNA vaccines. TO KNOW MORE

THEORY 6- The mRNA vaccine is a technology that has never been used in humans. (00008)

Author: Task Force Vaccine Published: 20/01/2021 Ref : 0019 EN FALSE !
In a review published in the journal Nature in April 2018 [1], numerous clinical trials, completed or in progress, using mRNA technology were already listed (10 trials in the framework of vaccine studies and more than fifty for the treatment of certain cancers).

In addition, studies of the mRNA-based COVID vaccine have enrolled more than 70,000 volunteers [2,3].
For the Pfizer-BioNTech vaccine alone, 43,734 volunteers were enrolled in the clinical trials: 21,937 received the vaccine and 21,797 received a placebo, providing sufficient data for Health Authorities to assess the vaccine's efficacy and safety and, following a rigorous review, to grant an Emergency Use Authorisation. ______________________________ Sources: 1-Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi: 10.1038/nrd.2017.243. Epub 2018 Jan 12. PMID: 29326426; PMCID: PMC5906799 2-Vaccines and Related Biological Products Advisory Committee Meeting, 2-2- December 10, 2020 FDA Briefing Document, Pfizer-BioNTech COVID-19 Vaccine
cf.: https://www.fda.gov/media/144245/download 3- Vaccines and Related Biological Products Advisory Committee Meeting, December 17, 2020, FDA Briefing Document Moderna COVID-19 Vaccine
cf.: https://www.fda.gov/media/144434/download

THEORY 7- mRNA vaccines present additional potential risks.

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 21/01/2021 Ref: 0020 EN FALSE ! The only adverse events that occurred in the volunteers tested in the study were minor and transient effects that are usually observed with other vaccinations [1,2]. Let's clarify the terms:

• Potential risk” is when an adverse reaction has occurred in animal studies BUT not in human clinical trials, or when an adverse reaction is known to be induced by a medicinal product of the same therapeutic class than the study product, BUT has not been observed in the study product (EMA, 2012 Good Pharmacovigilance Practices Annex I).

THEORY 8- Older people were not included in the clinical trials.

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 18/01/2021 Ref: 0021 EN FALSE !

• In the Pfizer-BioNTech vaccine trial mentioned in the FDA Briefing, it is stated that: 1712 patients over 75 years of age were included in the clinical trials, i.e. 4.3% of the total number (Table 4, p. 20) and that none of them subsequently contracted COVID 19 versus 5 in the placebo group (Table 9, p. 28). In addition, the Moderna group published similar results by including 1299 people over 75 years of age among its volunteers.
• Although these figures are not sufficient to certify the efficacy of the vaccine on the elderly, they are encouraging and consistent with the results observed in the lower age categories [1]. It is, moreover, important to note the similarity of the results of the two clinical trials in this age category [2].

THEORY 9- Mass vaccination is being carried out with experimental vaccines

Vaccine Safety Net Resources Author: Task Force Vaccine Published: 19/01/2021 Ref: 0022 EN

• Pfizer-BioNTech and Moderna vaccines can no longer be qualified as "experimental" vaccines at this stage. They now hold an Emergency Use Authorization granted by Health Agencies after a rigorous review of basic research data, animal studies results, and clinical trials Phase 1, 2, and 3 results,involving a very large number of volunteers.

Why is six feet away the right distance?

Author: Task Force vaccine Published: 20/01/2021 Ref: 0012 EN The coronavirus spreads primarily through droplets from your mouth and nose, especially when you cough or sneeze. Six feet has never been a magic number that guarantees complete protection. The C.D.C., one of the organizations using that measure, bases its recommendation on the idea that most large droplets that people expel when they cough or sneeze will fall to the ground within six feet. But some scientists have looked at studies of air flow and are concerned about smaller particles called aerosols. They suggest that people consider a number of factors, including their own vulnerability and whether they are outdoors or in an enclosed room, when deciding whether six feet is enough distance. Sneezes, for instance, can launch droplets a lot farther than six feet, according to a recent study. It's a rule of thumb: You should be safest standing six feet apart outside, especially when it's windy. But keep a mask on at all times, even when you think you’re far enough apart. Ref :
New York Times : Answers to Your Current Coronavirus Questions
Jamanetwork : Turbulent Gas Clouds and Respiratory Pathogen Emissions

Pfizer and Moderna vaccines contain lipid nanoparticles. Do they present risks?

Author: Ilan Bloch and Task Force Vaccine Published: January 23, 2021 Ref: 0005 EN The liposomes in which the messenger RNA is enclosed are well tolerated by the body and used in 30% of tablet drugs, shampoos and toothpastes etc..... This is Polyethylene Glycol which is very widespread [1] T To know more: Nanoparticles" are all particles between 1 and 100 nanometers in size - this is the order of magnitude of many viruses. Tolerance to nanoparticles depends largely on their composition. Some are highly toxic, such as those from tobacco smoke or diesel engines. The lipid nanoparticles used in messenger RNA vaccines are about 80 nanometers in size and are made of lipids similar to those found in the human body; they do not contain metals (silver, titanium, gold, etc...). Swissmedic [2], the Swiss drug regulatory agency, considers these lipid nanoparticles to be well tolerated by the body, as they are already used in several drugs approved in Switzerland (including drugs used in cancer treatment). Their medicinal use in Switzerland is strictly regulated by Swissmedic. References 1-Ref: * BJA. Allergic reactions to the first COVID-19 vaccine: is polyethylene glycol (PEG) the culprit? 2- i nfovac.ch - Swiss information plateform on viruses.

Is there any other possible solution than vaccination?

Summary of the Vaccine Safety Net resources Author: Task Force vaccine Published: 19/01/2021 Ref: 0007 EN

• What about medication?
  As for today, some treatments and medication help in assisting COVID patients but none of them has proven full efficacy in treating patients with severe symptoms and preventing complications or death. It is therefore crucial to stop the pandemic.
  But, as for today, no treatment has been proven effective to prevent the infection.
  
• What about vaccines?
  Clinical trials of the vaccines showed vaccinated persons were protected from getting Covid with a very high efficacy (up to 95% with the Pfizer-BioNtech and Moderna vaccines) Therefore, the vaccine is the most advanced way to end the pandemic.
  
• What about the wearing of mask on mouth and nose and social distanciation*?
  Those measures help reduce our risks of being exposed to the virus or spreading it to others, But, only associated to COVID vaccination, will those measures offer the best protection from COVID,

Is Covid-19 less dangerous than the mRNA vaccine used against it?

​​​​​​​ Author: Task Force on Vaccine​​​​​​​ Published: January 12, 2021 Ref: 0002 EN To this day, almost everyone knows someone who had a serious form of Covid-19 that is requiring hospitalization or even resuscitation, and many families have lost one or more loved ones. In addition, doctors have warned of the risk of collapse of the Healthcare system. In 2020, ethics and the need for care for the population do not allow us to consider this pandemic as benign. Regulatory agencies, FDA, EMA and MHRA and more agencies, have analyzed the vaccine development in real time and in an extremely rigorous manner. Efficacy results have been exceptional since the FDA required 60% efficacy and the new vaccines have demonstrated 95% efficacy with short-term safety comparable to other existing vaccines. This is a first of its kind in medicine. Of course, there are still unknowns about the long-term effects on efficacy and safety. Experts in all fields, including immunologists, hematologists and geneticists, have made the decision to give authorization to use these vaccines, weighing the benefits and the risks of the vaccine against the risk of the disease and emphasizing very close monitoring of the vaccinated individuals.

Can there be a causal link between vaccination and the onset of an autoimmune disease?

Authors: Daniel Maller- Task Force Vaccine Published: 20/01/2021 Updated: 22/03/2021 Ref: 0010 EN The WHO Vaccine Safety Advisory Committee has established criteria to allow an objective definition of associations between vaccination and adverse reactions. They also apply to autoimmunity problems. The assessment of autoimmune events should be accurate, based on rigorous analytical methods and sufficient data. It may be a coincidence that a side effect appears soon after a vaccination. Such undesirable events should be considered as side effects only if a significant association is demonstrated by epidemiological studies on different populations, in order to verify the hypotheses put forward on the basis of isolated cases. There are only 3 rare autoimmune diseases for which an association with vaccines has been shown:

• Guillain-Barré syndrome (neuropathy) which is a known complication of influenza, and can occur exceptionally after vaccination against influenza.

Is the muscle cell transfected with the S-antigen producing mRNA endangered?

Authors: Daniel Maller- Task Force Vaccine Published: 20/01/2021 Updated: 22/03/2021 Ref: 0004 EN Following injection of the vaccine, a small minority of muscle cells receive, not the virus, but one of its messenger RNAs, which will direct the synthesis of the "Spike" protein. The cells then expose this antigen on their surface and present it to the incoming immune cells, which identify it as foreign, and trigger a specific response of CD4 (helper) et CD8 (killer) T lymphocytes. The messenger RNA is quickly degraded, which stops the expression of the Spike protein: it is not renewed on the surface of the cells, and hence disappears rapidly. The immune response takes a few days to develop. The tiny minority of muscle cells that still display the Spike antigen on their surface are then eliminated by cytotoxic CD8 lymphocytes, and replaced according to the usual healing process. References Leitner, W.W., Ying, H., Restifo, N.P. DNA and RNA-based vaccines: principles, progress and prospects. Vaccine 18, 765-777 (1999). Pardi, N., Hogan, M.J., Porter, F.W., Weissman, D. mRNA vaccines – a new area in vaccinology. Nature Reviews – Drug Discovery 17, 261-279 (2018). Wiendl, H., Hohlfeld, R., Kieseier, B.C. Immunobiology of muscle: advances in understanding an immunological microenvironment. Trends in Immunology 26, 373-380 (2016).

Is mRNA vaccine a vaccine or a gene therapy?

Authors: Menahem Brégégère, PhD, Molecular biology & genetics Irène Fermont, MD, Pharmacovigilance Published: January 12, 2021 Ref: 0026 EN Vaccination with mRNA has nothing to do with gene therapy. Gene therapy introduces genetic material in order to correct or replace a defective gene, as a treatment of genetic disease or cancer. Pfizer vaccine mRNA enables cells to temporarily express the spike protein at their surface. It does not enter the nucleus. This limited exposure of the antigen is sufficient to trigger the immune response, without interference with cellular gene structure or function. This vaccine confers immunity by means of a single protein. It does not introduce an infectious agent, even inactivated, into the cells. This new technology therefore has definite advantages in terms of specificity and safety. SHOW MORE

What are the mRNA vaccine side effects?

Summary of the Vaccine Safety Net Resources Author: Task Force on Vaccine Published: January 12, 2021 Ref: 0008 EN NB : In February the CDC and the EMA have published a first report on spontaneous adverse events reported since the beginning of the vaccination campaign . This question is currently under revision and will be updated soon. Minor to moderate secondary effects may occur after vaccination as they may occur after any vaccination; those side effects are a sign that the immune system is building up protection to the disease. They may affect your ability to do daily activities, but should resolve within a few days. The regulatory authorities in most countries have set up extensive monitoring of the vaccinated people and track continuously the eventual occurrence of rare unexpected events with COVID vaccines. In the clinical trials, the following side effects have been described: 1- Common side effects on the arm where you got the shot

• Pain

Who should get or not get the COVID-19 vaccine ?

Summary of the Vaccine Safety Net Resources Author: Task force Vaccine Published : January 12,2021 Updated: 31/01/2021 Ref: 0011 EN Most people are able to get the COVID-19 vaccine. But, a few groups of people should not get the vaccine, some should not get the vaccine for the time being and others should consult with their doctor and eventually follow special procedures. 1 - People who should NOT get the vaccine: - Anyone who had a previous anaphylactic shock or a strong allergic reaction to a previous SAME vaccine (includes people who had a severe allergy to the 1st dose of the vaccines. Those people shouldn’t get the 2nd one) - Anyone with a severe allergy to any component of the COVID vaccine 2 - Persons who should NOT get the vaccine for the time being - People below 16 years of age because a too small amount of data is presently available - People isolated or with COVID symptoms; they must wait after isolation ends and/or symptoms resolve - People who recently had COVID; they-must wait until 90 days after treatment is over. NB According to the countries it may be recommended or not to vaccinate people who had COVID. Check the recommendations in your country.
- People who may get the vaccine after their doctor carefully considered their individual risks and benefit - Pregnant women and breastfeeding: due to the small amount of data during the clinical trials, it was not recommended to get the vaccine at the time of authorisation by regulatory agencies. - Then with the occurrence of several severe cases of COVID 19 in pregnant women, several countries are now recommending the vaccination in pregnancy and breastfeeding women.It is considered that pregnancy is in itself a risk of getting severe forms of COVID 19. This is the case in Israel and in the USA where the regulatory authorities recommend the vaccination after the 1st quarter of pregnancy and in breastfeeding. In France, the association of obstetricians has reached the same conclusion, but it is not yet officially recommended by the French regulatory authorities. Therefore, especially when breastfeeding or pregnant women present a high risk of getting a complicated COVID-19 either because of underlying disease or any other reason, the doctor could consider the individual benefit and risks. In addition it is admitted to consider vaccination for any pregnant woman who will desire it. According to the countries it may be possible or not to vaccinate pregnant and breastfeeding women. Check the recommendations in your country. - People with history of severe allergy (requiring medical intervention) to any vaccine or any injectable medication or non-injectable substance; they should consult their doctor prior to vaccination and remain under medical surveillance at the vaccination location for 30 min after injection - People with HIV - People with certain immune-compromising conditions - People on anticoagulants: a special procedure is described in
Sources : CDC : https://www.cdc.gov/coronavirus/2019-ncov/hcp/vaccination.html UK Government: https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a WHO : https://www.who.int/publications/m/item/who-sage-roadmap-for-prioritizing-uses-of-covid-19-vaccines-in-the-context-of-limited-supply Hospital of Philadelphia : https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/prevent-covid?utm_source=prevent-covid&utm_medium=redirect&utm_campaign=VECCOVID Israeli Ministry of Health French College of Obstetricians

How could COVID vaccines be developed so quickly?

Summary of the Vaccine Safety Net Resources Author: Task Force Vaccine Published: 19/01/2021 Ref: 0010 EN COVID vaccines were developed at a record speed while maintaining standards for safety and efficacy. The reasons behind this rapid progress include: 1- Research had started years ago The biggest misconception is that the work on the vaccine started when the pandemic began but research on Coronaviruses and on anti-Coronaviruses vaccines started more than a decade ago. The collected data have been used in the COVID19 vaccine development. 2- mRNA technology Technology has evolved to make development faster. Previously, viral vaccines could only be developed after growing the virus in a laboratory. Newer technologies build vaccines using the genetic code for the virus; thus, researchers could start as soon as the genome for the virus was released in January 2020. 3- Pandemic make clinical trials progress quickly Clinical trials involve the comparison of both safety and efficacy of the tested vaccine on a vaccinated group and an unvaccinated group. They progress more quickly if a disease is widespread, as is the case with COVID-19 in many countries, as a significant difference between the unvaccinated and vaccinated groups can be detected sooner than for a rare disease. 4- Parallel steps instead of sequential steps The different clinical development steps (phases 1, 2 and 3), the building of the production facilities and the production of the vaccine itself have been handled in parallel, making the process faster. In addition, the regulatory review of the data has been conducted phase by phase, without waiting for the end of the whole process. 5- Unprecedented international funding and collaboration between vaccine developers and governments around the world. Huge financial risks have been taken, such as building manufacturing facilities before a vaccine was even available and funding the research on a very large scale. Funding was coming from governments, WHO, foundations and industry. To ensure global equity to the access of the vaccine, WHO is leading COVAX, a global research platform of 75 countries, pooling international resources, accelerating development, production, and giving equitable access to tests, treatments, and vaccines. Sources WHO : https://www.who.int/news-room/q-a-detail/coronavirus-disease-(covid-19)-vaccine-research-and-development CDC : https://www.cdc.gov/vaccines/covid-19/hcp/prepare.html Australian Government : https://www.ncirs.org.au/covid-19/covid-19-vaccine-development-landscape

Are there risks of narcolepsy with COVID-19 mRNA vaccines?

Author: Task Force Vaccine Published: 24/01/2021 Update: 07/03/2021 Ref: 0024 EN

• No case of narcolepsy has been observed in clinical trials with COVID-19 mRNA vaccines, nor has been subject of warning to health agencies since the vaccination campaign started.

• Cases of narcolepsy were observed during the 2009-2010 H1N1 influenza epidemics following vaccination with Pandemrix® influenza vaccine. The number of cases in Europe is estimated at 650 out of 19 million people vaccinated, i.e. around 3 per 100,000. It is therefore an extremely rare phenomenon.
• Pandemrix® influenza vaccine is an attenuated virus vaccine (fragmented virion, inactivated, with adjuvant). Its responsibility in recorded cases of narcolepsy has been much debated, particularly by the US CDC, but appeared to be confirmed primarily in children and adolescents.

What is still unknown regarding the Covid-19 mRNA vaccine?

Author: Task Force Vaccine Published: 24/01/2021 Update: 07/03/2021 Ref: 0025 EN Health Agencies (FDA, EMA, MHRA) have decades of experience in the area of vaccine safety. These agencies have granted an Emergency Use Authorization for two vaccines that have achieved excellent results in clinical trials, both in terms of efficacy (over 90%) and in terms of safety. Some questions remain (see section For more information), and there is, as always, a low risk of long-term, unwanted effects that were undetected in animal studies or in clinical trials. However, it is crucial that this potential risk, present in any vaccine or medication , be assessed in comparison with the known and proven risks of mortality and morbidity, direct and indirect, linked to COVID19. Monitoring of side effects (pharmacovigilance) has been greatly improved in most countries, particularly in Israel where 90% of medical data are digitized, which allows a quick detection of warning signals. To date (March 3, 2021 ), after more than 300 millions of vaccines doses have been administered, patients have been closely monitored, COVID vaccines are estimated to be particularly safe. It should also be noted that the rapid development of mRNA vaccines is a major innovation that could allow: very rapid editing and renewal of current vaccines when mutations emerge, development of new treatments for certain cancers. - The mRNA technology is a historical breakthrough in the history of the medicine which opens a large field of new research . It is believed that its features may help saving millions of human lives. For more information Additional studies are scheduled that will allow further elucidation of certain questions, such as: - How long does the vaccine provide immunity? - Can vaccinated people transmit the virus? - What categories of people that were insufficiently or not represented in clinical trials (such as children and pregnant women), should be vaccinated? Update: The pharmaco-epidemiologic data coming from the countries where vaccination has been implemented have started to answer some of these questions and will soon bring more answers. Israel is leading the mass vaccination and, having 90% of the medical data digitalized, has already: - confirmed the efficacy of the clinical trials when vaccination is performed in real life - confirmed the safety with no new signals - started to vaccinate pregnant women and teens over 16 years of age - observed a drastic decrease of infection in the vaccinated people - a decrease of serious cases or mortality n the population at risks

What makes mRNA vaccine safe?

Author: Task Force on Vaccine Published: 25/01/2021 Update: 07/03/2021 Ref: 0023 EN The vaccine safety derives from its mechanism of action. Indeed : - Anti- COVID19 mRNA vaccines convey only one strand of messenger RNA instead of the whole viral RNA in a viral infection. This mRNA encodes only one protein, the Spike protein which is immunostimulant and non-pathogenic. The low risks associated with inactivated or attenuated viruses in conventional vaccines, are therefore irrelevant to these mRNA vaccines.The vaccine mRNA is free of all viral components,since it was synthesized in laboratories where the virus itself never entered. - After cell penetration, the vaccine mRNA remains in the cytoplasm, and being very labile, it is qickly eliminated. It never enters the nucleus, has no contact with DNA, and no access to the keys that allow interaction with DNA especially reverse transcriptase. This point is confirmed by all regulatory agencies that have granted emergency use authorization (FDA, EMA, MHRA.): mRNA does not enter the nucleus and it cannot act on the human genome. CDC, https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html

Can RNA vaccines be administered subcutaneously?

Author: Daniel Maller and Task Force Published: 23/03/2021 Ref: 0033 EN No. The vaccine must be injected strictly intramuscularly. In subjects with a hemostasis or coagulation disorder, or in people on anticoagulants, the vaccination can be done in the deltoid muscle with a fine needle (ideally 25G), followed by strong and prolonged compression ( 2 minutes). People with particularly severe hemostasis or coagulation disorder, which is a contraindication to intramuscular injection, should not be vaccinated unless the potential benefit clearly outweighs the risks associated with the injection. References : Lowe, D. mRNA vaccines: What happens. Science Translational Medicine (21 January 2021). https://blogs.sciencemag.org/pipeline/archives/2021/01/21/mrna-vaccines-what-happens

What is the efficacy of mRNA vaccines?

Summary of the Vaccine Safety Net Resources Author: Task Force Vaccine Published: 18/01/2021 Ref: 0006 EN All following results on efficacy in the clinical trials have been obtained in the same level, in all groups, ethnicities, and genders. Moderna vaccine

• Moderna vaccine efficacy was tested on 30,000-person.
  Only 11 who received the vaccine developed symptoms after being infected vs. 185 in a placebo group. That is an efficacy of 94.1%!
• Moderna’s vaccine showed 100% efficacy against severe forms of the disease:
  0 such cases among those vaccinated vs. 30 in the placebo group, inc. 1 death from the disease.

Why are scientists not unanimous?

Author: Task Force Vaccine Published: 20/01/2021 Ref: 0001 EN It is the nature of science to make hypotheses and try to verify them.
“A theory that is not refutable by any conceivable event is non-scientific. Irrefutability is not a virtue of a theory (as people often think) but a vice. (...) The criterion of the scientific status of a theory lies in its falsifiability, or refutability, or testability.“ (Karl Popper)


In physics, for instance, a theory is valid as long as the results of the equations fit with the results of the experiments.
In vaccine science, a vaccine is considered legitimate if it is safe and effective. It is scientifically correct to evaluate Covid vaccines according to these criteria and then to discuss the sample size and the monitoring time allowing to include these vaccines in the therapeutic arsenal.
It is therefore normal and even recommended that scientists "argue". But it is dangerous for them to do so publicly because their field of expertise involves complex notions and a specific language that only them are able to understand. Putting up contradictory arguments is legitimate, but making it publicly invalidates public confidence.
A physician or scientist should not use social networks to express non-evidence based theories in conflict with Public Health decisions, especially during a global pandemic. By doing so, he or she is participating in what he or she denounces.

What should we know about new variants of COVID?

Author: Menahem Bregegere,PhD, Contributors: Irene Fermont MD, MSC, Ayalah Livneh MD, MSc Published : 31 January 2021 Update: 07/03/2021 0027 EN Virus mutations are errors in the replication of their genetic material. Most are harmless, but some can change virulence, and/or virus susceptibility to the immune response.(1) The COVID-19 "Spike" is a strategic protein, by which the virus binds to the "ACE2" receptor of the cells it infects, in order to enter them. Spike affinity for the receptor is accountable for virulence.(2) Spike is the preferred target of anti-viral immunity. Therefore Pfizer and Moderna have chosen its messenger RNA as the active ingredient of their vaccine, in order to trigger an intense and well-targeted immune response.(3) In September 2020, a high virulence variant of COVID-19, "B.1.1.7", appeared in Great Britain. It has spread rapidly, and is accountable today for the majority of new infections in Israel. This variant contains 17 mutations, compared with the original Wuhan strain, including several in the receptor binding domain of Spike – the area of contact with the cell it infects. These mutations are likely to increase virulence.(4) They are also likely to let the virus escape the immunity acquired from a primary infection with the original virus, or from a vaccination. However, laboratory experiments with the B1.1.7 variant showed that the neutralizing power of antisera from convalescent COVID, or from people vaccinated with Pfizer or Moderna vaccines, was barely attenuated.(5) The protection provided by the vaccines against this variant is therefore essentially intact. The main problem raised by B1.1.7 is its high transmissibility, which increases contagion and multiplies the number of patients at all levels of severity.(6) In addition, health authorities also raise the possibility of higher virulence, with serious complications observed in pregnant women, and possibly also in children,(7) (8). Finally, preliminary results suggest that this variant tends to increase COVID severity and death rate.(9) 1) cles/d41586-020-02544-6 Callaway, E. 2020. Making sense of coronavirus mutations. Nature 585, 174-178. https://www.nature.com/arti 2) Starr, T. N., Greaney, A. J., Hilton, S. K., et al. 2020. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell 182 (5) 1295-1310. https://www.cell.com/cell/fulltext/S0092-8674(20)31003-5 3) Du, L., He, Y., Zhou, Y., et al. 2009. The spike protein of SARS CoV – a target for vaccine and therapeutic development. Nature Reviews Microbiology 7, 226-236. https://www.nature.com/articles/nrmicro2090 4) Corum, J., Zimmer, C. 2021. Inside the B.1.1.7 coronavirus variant. The New York Times (18/01/2021. https://www.nytimes.com/interactive/2021/health/coronavirus-mutations-B117-variant.html 5) Muik, A., Wallischn A. K., Sänger, B., et al. 2O21. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited sera. Science 10.1126/science.abg6105 (2021) https://science.sciencemag.org/content/early/2021/01/28/science.abg6105 6) Galloway, S. E., Prabasaj, P., Mac Cannel, D. R., et al. 2021. Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021. CDC – Morbidity and Mortality Weekly Report. https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm 7) Christensen, J. 2021. CDC doesn't know if new Covid-19 variants are causing rare complication in children. CNN Health (27/01/2021) https://edition.cnn.com/2021/01/27/health/new-covid-variant-complications-children-wellness/index.html 8) Jaffe-Hoffman, M. 2021. Coronavirus: Gov't to vote on full closure of airport today. Jerusalem Post (24/01/2021) https://www.jpost.com/health-science/coronavirus-six-pregnant-women-in-serious-condition-have-uk-variant-656461 9) Iacobucci, G. 2021. Covid-19: New UK variant may be linked to increased death rate, early data indicate. British Medical Journal, 372, n230 https://www.bmj.com/content/372/bmj.n230 Another variant appeared in South Africa in October 2020, named "501Y.V2". This variant has some mutations of the Spike in common with B.1.1.7, as well as an increased transmissibility, and it has more mutations in the Spike (8 in all) (10) , that allow it to partially escape immunity acquired from a primary infection(11). Laboratory studies have shown that sera from people who have received Pfizer or Moderna vaccines partially neutralize viruses carrying the 501.Y.V2 mutations (12) (13). But these results cannot simply be extrapolated to real life, leaving us in doubt about the effectiveness of these vaccines on the variant. Other variants with increased transmissibility have appeared, notably the Brazilian variant P.1, which has many features in common with 501.Y.V2 although it appeared independently;(14) the California variant CAL.20C, which shares mutations with B.1.1.7;(15) and probably others still, which have not yet been characterized. All these variants are already present in Israel, although in marginal amounts, and are expected to spread in the coming period. They therefore constitute a challenge that we will have to take in the near future. To achieve this, vaccines and social distancing measures are good tools. A major advantage of the mRNA vaccine is its adaptability: virus attempts to evade immunity can be thwarted by using an mRNA where variant mutations have been introduced. The site-directed mutagenesis technique makes this possible in a very simple manner.(16) Therefore Ugur Sahin, CEO of BioNTech, could say that he was "technically capable of delivering a new vaccine in six weeks".(17) The battle against the pandemic is therefore not over. It is well underway, but we have not yet won the war. 10) Tegally, H., Wilkinson, E., Giovanetti, M., et al. 2020. Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. medRxiv Preprint doi: https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1 11) Wibmer, C. K., Ayres, F., Hermanus, T., et al. 2021. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. bioRxiv Preprint doi: https://www.biorxiv.org/content/10.1101/2021.01.18.427166v2 12) Pfizer. In vitro studies demonstrate Pfizer and BioNTech vaccine elicits antibodies that netralize SARS-CoV-2 with key mutations present in U.K. and South African variants. 27/01/2021. https://www.pfizer.com/news/press-release/press-release-detail/vitro-studies-demonstrate-pfizer-and-biontech-covid-19 13) Moderna Inc. Moderna COVID-19 vaccine retains neutralizing activity against emerging variants first identified in the U.K. and the Republic of South Africa. 25/01/2021. https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against/ 14) Faria, N., Claro, I. M., Candido, D., et al. 2020. Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings. Virological.org. https://virological.org/t/genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-manaus-preliminary-findings/586 15) Zhang, W., Davis, B. D., Chen, S. S., et al. 2021. Emergence of a novel SARS-CoV-2 strain in Southern California, USA. medRxiv Preprint doi: https://doi.org/10.1101/2021.01.18.21249786 16) Hemsley, A, Arnheim, N., Toney, M. D., et al. 1989. A simple method for site-directed mutagenesis using the polymerase chain reaction. Nucleic Acids Research 17 (16), 6545-6551. https://pubmed.ncbi.nlm.nih.gov/2674899/ 17) Jordans, F. 2020. BioNTech CEO confident vaccine will work on UK variant. AP News, December 22, 2020. https://apnews.com/article/europe-europe-coronavirus-pandemic-united-states-8555f433c0cd8ea8c58040e3f7aa0e91

Covid 19  and Pregnancy/fertility: What is currently known? - Data extracted from Pfizer/BioNtech and Moderna Covid19 vaccine trials

Author: Task Force Vaccine Published: 19/01/2021 Ref: 0017 EN Questions have been recently raised related to the fertility of women receiving the Covid-19 Vaccine. While some studies have attempted to address the issue of reproductive impact of patients with Covid-19 (biological and psychobehavioral)[1], we present below what is known to date...
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Is there a risk for women fertility with Pfizer-Biontech vaccine?

Summary of the Vaccine Safety Net Resources Author: Task Force Vaccine Published: 24/01/2021 Ref: 0009 EN - Reports on social media have falsely asserted that the vaccine could cause infertility in women. It has been feared that this misinformation may cause women to avoid vaccination to prevent COVID-19, which is a potentially serious and life-threatening disease. - There is no scientific evidence to suggest that the vaccine could cause infertility in women. - In addition, infertility doesn’t occur as a result of COVID disease, demonstrating that immune responses to the virus, induced by infection or vaccine, cannot become a cause of infertility.
- The vaccine mechanism involves an immune reaction against the so-called Spike protein, a characteristic protein of the COVID 19. Contrary to false reports on social media, this protein to which the body opposes is not the same as any other protein involved in the formation of the placenta. Source: FDA : https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/pfizer-biontech-covid-19-vaccine-frequently-asked-questions

I am pregnant, what are the risks if I contract COVID-19?

Task Force 02/03/2021 Ref: 0035 EN Regarding the unborn child, some studies suggest that there is an increased risk of prematurity, intrauterine growth retardation or neonatal death. While SARS-CoV-2 infection may be a contributing factor, factors specific to the mother or to the course of the pregnancy may also be involved. As the studies available on the subject are still incomplete, it is advisable to be careful and to ensure a good follow-up of the pregnancy. The potential impact of the virus earlier in pregnancy has also been poorly studied to date. So far, transmission of the virus in utero to the unborn child has only been reported and confirmed in two pregnant women, according to international literature. The scientific community remains cautious, believing that if this route of transmission is possible, it is very rare. In practice, the virus is transmitted more often in the very first hours after birth, through direct contact between the infected mother and her newborn. The course of the disease in the newborn is not serious in the vast majority of cases. https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/pregnancy-and-covid-19/art-20482639

What do we know about vaccination of pregnant women against COVID 19?

Authors: Raphaelle Beau Ledjstrom PhD, Irene Fermont,MD,MSC Published: 31/01/2021 Update: 23/03/2021 Ref: 0037 EN Pregnant and lactating women were not initially included in the phase 2-3 trials of the mRNA vaccines. Use during pregnancy and lactation therefore appears as missing information. However, 36 pregnancies occurring during the trial were reported during follow-up (18 for the vaccine arm versus 18 for the placebo when the Pfizer / BioNtech and Moderna data are added together). The results have not shown any imbalance of new pregnancies between the two arms (vaccine versus placebo) and to date no significant pregnancy problem that could be related to the vaccination. However, 36 pregnancies occurred during the follow-up (18 among those who received the vaccine, and 18 among those who received the placebo, when Pfizer / BioNtech and Moderna data are merged). To date, the results have not shown imbalance of pregnancy numbers between the two groups (vaccine versus placebo), nor significant complications attributable to vaccination, albeit pregnancy follow-up has been short, and data is still limited at this stage. After the spread of new variants, and the increase in serious symptoms and death in pregnant women, they are now considered as a population at risk. The journal Nature reports a study from September 2020, carried out on 11,400 women hospitalized for COVID 19, which shows that the probability of being admitted to an intensive care unit (ICU) is 62% higher for pregnant women at the same age, while the probability of being placed on a respirator is 88% higher. Another study has shown that pregnant women who contract COVID 19 are three times more likely to give birth preterm. Taking this into account, the Israeli Ministry of Health has issued the following guidelines:

1. There is no evidence to suggest that the vaccine has any harmful effects either to the fetus or to the course of pregnancy, at any stage of the pregnancy, and there is no recognized biological mechanism that may indicate such a possibility.
2. It is recommended to vaccinate breastfeeding women.
3. It is recommended that women who are planning a pregnancy or who are undergoing fertility treatments complete the two vaccine doses before the beginning of the pregnancy.
4. In the case of a woman who received the first vaccine dose and then discovered that she is pregnant, it is recommended that she will receive the second vaccine dose according to the regular vaccination schedule.
5. We recommend vaccinating pregnant women who are considered as being at high-risk for infection (healthcare workers or any other group defined as high-risk by the Ministry of Health) or being at risk for severe illness (due to such pre-existing conditions as: obesity, pre-maternal diabetes, hypertension, etc.).
6. It is our recommendation to vaccinate all pregnant women in their second or third trimester.
7. The first trimester (regardless of coronavirus disease) is characterized by a relatively high rate of bleeding incidents, spontaneous miscarriage, and the appearance of fetal abnormalties. In order to prevent ant link, albeit incidental, between vaccination and these phenomena, it is our recommendation only to vaccinate pregnant women who do not belong to any of the high-risk groups detailed in article 5 above, starting at the second trimester.
8. In case of women who plan to undergo an amniotic fluid test, it is recommended that they refrain from vaccination around the time of the scheduled test (it is recommended to leave a buffer of at least one week between the vaccination and the test) in order to avoid fever or any other side effects which may be interpreted as complications to the tests.
9. Due to the severity of the coronavirus disease and its harmful effects, we reiterate our recommendation for the entire population, and women in the age of fertility, pregnant women, and breastfeeding women in particular, to continue following the social distancing and masking rules and thereby reduce their risk for exposure and infection with coronavirus disease.