Long-term Vaccine Safety: the Facts

Still commonly shared online, the claim that we don't know the long-term side effects of  Covid vaccines is untrue. In fact in the scientific and medical world, a year is considered 'long-term' when it comes to vaccine safety.

It is now (25th Feb. 2022) more than 14 months since the first Covid-19 vaccine dose was given, and a year since the first delivery of Covid-19 vaccines under the Covax scheme. Scientists explain that this is more than enough time for all but the rarest side effects to have emerged. 

In fact the number of people who have received vaccine is more important than the length of time vaccines have been in use. New vaccines undergo stringent procedures to identify (a) whether it works, (b) if there are any side effects and (c) are the side effects mild or severe. In normal times, vaccine trials have gaps between the different stages due to researchers obtaining funding for the next stage. With Covid-19, funding was made instantly available, thus shortening the time from concept to production.

What happens in your body?

Covid vaccines may be new, but the processes they trigger in your body are not, and we know how the immune system works. Understanding how they stimulate the immune system can help us understand how quickly we can expect to have any negative reactions. 

After 15 minutes

• A tiny fraction of people will have an allergic reaction to the inactive ingredients in the vaccine and this will happen within about 15 minutes of receiving it.

After a few hours

• Shortly after receiving the vaccine, the immune system recognises an alien invader and attacks it with immune cells, the weapons it would use against any virus or bacteria.
• In this innate phase, any reactions will happen within hours or a couple of days, including the most common side effects of a sore arm, temperature and other flu-like symptoms.
• Also in this phase is a much rarer side effect which has been linked to the mRNA vaccines Moderna and Pfizer is myocarditis (inflammation of the heart).
• While the exact cause of myocarditis is not understood, inflammation is one of the body's responses to infection or injury.
• Vaccine induced mycarditis is generally mild, and gets better on its own or with basic anti-inflammatory drugs such as ibuprofen.

After 10 days

• The innate phase also starts the second phase of your immune response - the adaptive phase - where your body starts to make cells which are specifically tailored to fight off the target virus. 
• As this phase starts around 10 days after infection, which is why vaccines will take this length of time to begin to have an effect in protecting you against Covid. 
• Your body pumps out new immune cells, peaking after about two weeks and fading away after about 28 days. 
• A very rare but serious side effect linked to the Astra-Zeneca vaccine (a specific type of blood clot) happens during this phase and is related to the antibodies produced by your immune system in response to the vaccine. That is why most of these rare clots have been seen within four weeks of vaccination.

By 28 days

• Once the adaptive phase dies down - after about a month - you are left with memory cells which give you protection for months or years after initial exposure but don't generate new responses. If you have not a reaction after the first couple of months, it is incredibly unlikely that anything that happens after that will be caused by the vaccine.
• While there is never a 100% guarantee with anything in medicine, vaccination history shows that most side effects occur within hours of receiving the vaccine, and rare side effects within days or weeks.  

Will we identify new side effects?

• From our hundreds of years of knowledge showing how the immune system works, an individual who has not had a reaction to a vaccine in the first couple of months, is vanishingly unlikely to have any new side effects after that.
• Countries world wide have put systems in place to monitor side effects and to share that information with each other. 
• It is these systems that picked up both the blood clots and myocarditis, which are extremely rare with only a handful of cases per million doses.
• While milder symptoms (e.g. sore arm or temperature) are likely to be under-reported, the more severe side effects are thoroughly recorded.
• Billions of doses have already been given, so any side effect not yet seen would be rarer than one in a billion.
• While the vaccines have all completed the expected three phases of trials that usually take place before being offered to the general public, they are still being carefully monitored until at least 2023, to make sure even the rarest of events are identified.

And remember....
All the evidence suggests that the overall risks of catching Covid far outweigh any risks from the vaccine.

Source: Covid: How we already understand long-term vaccine safety by Rachel Schraer (BBC Health and misinformation reporter)

UK Covid Trial Tests Mixing Vaccines

February 2021: A UK trial has been started to see if giving people different Covid vaccines for their first and second doses works as well as the current approach of giving the same type of vaccine twice.

If there is a proven benefit it would (a) provide more flexibility with vaccine rollout and help deal with any potential disruption to supplies, and (b) scientists say mixing vaccine jabs might also give better protection. No changes would be made to the UK's current approach until at least summer 2021.

Current official guidance from the Joint Committee on Vaccination and Immunisation (JCVI) is that anyone who has had a first dose already should be given the same vaccine for their second dose. (In rare circumstances a different vaccine can be given - if only one vaccine is available or it is not known which was given for the first dose.)

Why is the trial happening? Scientists have good reason to believe that mixing vaccines may prove beneficial; some Ebola immunisation programmes already involve mixing different jabs to improve protection. In the UK mixing doses has happened historically with vaccines for hepatitis, polio, measles, mumps and rubella.

Study details. The Cm-Cov study is run by the National Immunisation Schedule Evaluation Consortium and will involve over 800 volunteers over the age of 50 in England. Some will receive the Oxford jab followed by the Pfizer jab, or vice versa. Some will have the jabs four weeks apart and others 12 weeks apart. Other vaccines may be added to the trial as they are approved by regulators. Results are likely to be published during summer 2021. 

Volunteers will be monitored for side-effects and blood tests will check how well their immune systems respond. They are currently being recruited in London, Birmingham, Liverpool, Nottingham, Bristol, Oxford and Southampton.

Why this approach could work. Animal studies have shown a better antibody response with a mixed schedule rather than the same vaccine on both occasions. The trial will test if an enhanced immune response happens in humans, or at least that the response is as good as using the same vaccine twice.

The full study will continue for 13 months, but it is hope that initial findings can be announced by June 2021, and could inform the types of vaccines younger age groups are offered as their second dose. It will also provide data on:

• The impact of the vaccines on new variants.
• The effects of second doses at four and 12 weeks.

Source: BBC News 4 Feb. 2021. Covid trial in UK examines mixing different vaccines.  https://www.bbc.co.uk/news/health-55924433

Vaccine Update

Several vaccines have been developed and have been undergoing trials for safety and effectiveness in order that they can be licensed. Here is the latest information and I will continue to update this post.

Vaccines are usually cultured in animal cells (e.g. chicken eggs for flu vaccines). Work is ongoing to develop plant based methods.

Vaccine timings. All currently (Feb. 2021) approved Covid-19 vaccines require two doses. In trials these were 3 weeks apart. Early Jan. 2021. As immunity develops over time, the UK extended the time between first and 'booster' doses to 12 weeks. 13 Feb. 2021. France has decided to give only one 'booster' dose of vaccine to anyone who has had the virus, and therefore already has some antibodies.

I can't have a vaccine, as my immune system doesn't function as it should due to an immune deficiency or because taking immune-suppressing drugs for another illness (e.g. cancer). A possible alternative to a vaccine is entering final stage trials, with first results expected in spring 2021. Developed by AstraZeneca, this uses Covid-19 antibodies from a single Covid patient in the US. The hope is that it will provide protection for at least six months, and possibly a year. However, the therapy is significantly more expensive than vaccination and difficult to produce at scale, so unlikely to be used for the wider population. AstraZeneca has also suggested it could possibly be used in care home settings to protect residents if a case is identified. While vaccines take time to build immunity, this should work immediately, so could be used as a preventative measure.

I have severe allergic reactions and carry an Epipen. People with known severe allergic reactions can react to any vaccine (including flu vaccinations) and are advised not to have a Covid-19 vaccine. If they do suffer a reaction they are treated with drugs such as steroids or adrenaline.

Common misconceptions about vaccine testing. Because of the speed with which vaccines were developed, some people are concerned that not enough testing was carried out. This is not the case. All normal testing was carried out as it would have been in non-pandemic times. However, researchers were able to move from one phase to the next without having to spend months or years to get funding for the next stage trials. However, rare side effects (of any vaccines or other drug treatments) are not always encountered in trials and are only reported when being used for prevention or treatment in many times larger numbers.

Side effects

• Many vaccinations do cause minor side effects, which usually quickly go away on their own. Typically there is often some soreness at the vaccination site. The most common other side effects are mild fever, chills, feeling tired and joint and muscle aches. 
• Women may sometimes experience a delayed period. This reverts to normal after one affected cycle. This side effect is not confined to Covid-19 vaccines, and can happen with other vaccines (such as flu vaccines) as well.

Serious side effects are rare

• Serious side effects are extremely rare, affecting 1 or 2 people in 1 million.
• Although vaccines are tested in large scale trials before being approved for general use, it is possible for rare side effects to only emerge once much larger numbers of people receive a vaccination. 
• As some instances are extremely rare occurrences not related to a vaccine, researchers will check to see if there is a link, and if there is, what is causing it. 
• They will compare the reported cases with the normal incidence in a population. For example, blood clots. While it now appears there may be 1 in 250,000 people who suffer this with the Astra Zeneca vaccine, far more will get this from other causes: 1 in 2,000 women develop blood clots from taking the combined oral contraceptive pill, and 1 in 1,000 people from air travel. 
• The possible Astra-Zeneca blood cases review did not compare the number of vaccinated people with this syndrome with the rate in unvaccinated people. Two of the reported cases had pre-existing blood clotting disorders, while for the other cases it was not stated whether they had recently had a Covid-19 infection, which itself can cause increased blood clots.
• Most of the cases occurred in women under 55, a group that already has a higher rate of blood clots because the contraceptive pill raises the risk of them.
• Being infected with Covid-19 also carries far more risks of blood clots developing. Thus 7.8% of cases develop pulmonary embolism, 11.2% deep vein thrombosis, 1.6% strokes and c. 30% thrombocytopenia. If admitted to Intensive Care Units, c. 23% of cases have venous thrombolism.

Vaccines approved for use in UK: Oxford Univ./AstraZeneca # Pfizer/BionTech # Moderna #

Oxford.Univ and Astra Zeneca (approved 30 Dec. 2020) UK has ordered 100 million doses. Vaccinations begun 4 Jan. 2021.

• Type: Uses a harmless virus that infects chimpanzees.
• Doses: Two doses a month apart. (Overall protection from both dosage trials is 70%).
• Protection (1): Full dose followed by full dose. Trial data indicates 62% of trial participants appear to be protected. Analysis also suggests a reduction in numbers being infected without showing symptoms.
• Protection (2): Half dose followed by full dose. Two weeks after the second dose, more than 90% of trial participants appear to be protected. 
• Protection (3): Why is the low dose better? (A) The immune system may reject the vaccine, which is built around a common cold virus, if it is given in too big a dose. (B) A low shot then a high shot may be a better mimic of a coronavirus infection and lead to a better immune response.
• UK and Overseas Trial: Phase 2 showed a strong immune result in adults in their 60s and 70s, based on 560 adult volunteers. Phase 3 in progress. No-one getting the vaccine developed severe Covid-19 or needed hospital treatment.
• US Trial: More than 32,000 volunteers, mostly in America, but also in Chile and Peru. The vaccine was 79% effective at stopping symptomatic Covid disease and 100% effective at preventing people from falling seriously ill. There were no safety issues regarding blood clots. The vaccine provided volunteers over 65 as much protection as younger age groups. Trial report March 2021.
• Side Effects: Apart from minor side effects (soreness at injection site, and mild headaches, fever and aches that clear up quickly) none were reported in trials. Early April 2021: a small number of cases of rare blood clots and low platelet levels were reported. There were 79 cases and 19 deaths among more than 20 million vaccinations in the UK. This equates to 1 case per 250,000 people (0.004%) and 1 death per million. The EU investigated 62 cases of cerebral venous thrombosis and 24 cases of sphlanchnic vein thrombosis, of which 18 were fatal from around 25 million vaccinations in the EU and UK. It is thought that a condition similar to heparin induced throbocytopenia occurs. Both UK and EU regulators deemed the vaccine safe to continue using but recommended that where possible people under 30 should be offered a different vaccine. 
• Notes (1): Can be stored at fridge temperature, unlike the Pfizer and Moderna vaccines, enabling it to be distributed world wide. 
• Notes (2): The Oxford technology is more established, so the vaccine is easier to mass produce cheaply. Costs around £3 per shot, less than Pfizer (around £15) or Moderna (£25) vaccines.
• Notes (3): A batch of trial vaccine was more concentrated. To avoid wastage, and with regulator approval, volunteers were given smaller amounts for their first dose and a full second dose. Results indicate that this gave better protection. 

24 Jan. 2021: Oxford University potential new vaccine (RBD-SpyVLP). Early animal studies show it could be effective in lower doses, making it easier to make in large quantities and be used in conjunction with other vaccines. This type of vaccine is not a competitor for the first wave of vaccines, it is hoped that it could be a standalone vaccine or a booster for those with a different Covid vaccine. Tests also show it is highly resilient, stable at room temperature and can be freeze dried without damage. These properties mean it would reduce dependence on cold chain transport and storage and help with global distribution. (Source The I newspaper 24/01/2021).

Pfizer and BioNTech: Licenced for use in UK early Dec. 2020. First order of 10 million doses started to arrive in early December; a further 30 million doses already ordered. 

• First vaccinations: 8th Dec. 2020. Over 80 age group and hospital and health care workers.
• Contraindications: Anyone with a history of severe allergic reactions. Reactions like this are uncommon but not unknown with various vaccines, including flu vaccines.
• Type: RNA - virus genetic code (uses part of the Covid-19 genetic code)
• Doses: Two doses, three weeks apart.
• Protection: Trial data (based on the first 170 volunteers to develop symptoms) indicates that 95% protection is achieved seven days after the second dose. There is also emerging evidence that it protects against severe Covid, but this is based on only 10 cases.
• Trial: 42% of all participants are from diverse ethnic backgrounds and 41% are aged between 56 and 85 years old.
• Side effects: Myocarditis (heart inflammation) can occur after infection with Covid-19 (typically within three months of catching it), with males 12-17 most likely to do so; rate of this complication is c.450 cases per million infections. Myocarditis following a second dose of Pfizer vaccine is much less common with just 67 cases per million. Mild cases are usually treated with anti-inflammatory drugs such as ibuprofen, with most people recovering within a few months. 
• Notes: There are massive manufacturing and logistical challenges as the vaccine has to be kept in ultra-cold storage at below minus 80C.

Moderna: Licenced for use in UK 8th Jan. 2021. Each person needs two doses. Not one of the six the UK initially ordered; 17m now on order, should be available spring 2021. 

• Type: RNA - virus genetic code
• Doses: Two doses, four weeks apart.
• Protection: Trial data (based on the first 95 to develop symptoms) indicates 94.5% is achieved after the second dose, appears to be effective in older age groups.
• Notes: The vaccine remains stable at minus 20C for up to six months and can be stored in a standard fridge for up to one month.

Novovax: The UK has secured 60m doses, which will be made in Stockton-on-Tees in NE England. If approved, supplies are expected to be available in the second half of 2020.

• Type: Uses recombinant nanoparticle technology to grow harmless copies of the virus spike protein, teaching the body's immune system to recognise and fight the pandemic virus.
• Doses: Two doses three weeks apart.
• Protection: Trial data indicates 89.3% effective in large-scale UK trials, and that it is effective against the faster-spreading variant present in the UK, and the South African variant.
• Notes: 

Russia Sputnik V: Registered for emergency use in August 2020, although had only been tested on a few dozen people. December 2020: doctors, teachers and social workers are being offered Sputnik V in a mass inoculation campaign ordered by President Putin. Still in trial, so some Russians are wary of receiving it yet.

• Type: Uses a harmless virus that infects chimpanzees. Comprises two entirely different injections, using different 'vectors' or carriers each time. This puts extra pressure on producers as the first component is the most stable but the second needs strict temperature controls.
• Trials: Still in midst of safety and effectiveness trials.
• Data: Reported to be 92% effective.
• Notes: Must be stored at -18 C at least in its liquid form. A planned powder version is not yet being made in large amounts.

China CoronaVac: Produced by biopharmaceutical company Sinovac. Although already in use and being shipped to some Asian countries, it has yet to finish late-stage trials.

• Type: An inactivated vaccine, using killed viral particles to expose the immune system to the virus without risking serious disease response. It is a more traditional method that is used in many vaccines like rabies.
• Doses: Two are required.
• Trials: Stage 1 and 2 trials completed, stage 3 still in progress. Jan. 2021: trials in Brazil found it only 50.4% effective.
• Notes: Can be stored in a standard refrigerator at 2-8 C. Therefore like the Oxford-AstraZeneca vaccine is more useful to developing countries where ultra low temperature storage is an issue.

In development

• Canadian company Medicago has produced a Covid-19 vaccine. (Jan. 2021. No details on this.)
• Janssen (trial volunteers being recruited). Type: Uses a modified common cold virus.Trial: 6,000 volunteers to be recruited in the UK, as part of 30,000 worldwide to assess whether two doses are more effective.
• Codagenix, US: Single does nasal spray using a modified synthesised version of the virus to provoke an immune response. Feb. 2021: in Phase 1 trials.
• Valneva, France: Whole inactivated virus two-shot vaccine. This type of vaccine can be given to vulnerable populations at risk of allergic reactions. Feb.2021: in Phase 1 and 2 trials, with plans for testing on children.
• Inovio, US: Synthesised DNA version of Covid-19 spike inserted into DNA plasmids. Two-shot vaccine blasted into skin using re-usable 'gun'. DNA Vaccines don't require frozen storage, have a one-year shelf life at room temperature and up to five years in a refrigerator. Feb. 2021: in Phase 2 trials.
• CureVac, Germany. Uses mRNA built from naturally occurring nucleotides stabilised to induce a strong innate immune response. A portable mRNA printer is also being developed to rapidly manufacture doses where vaccine is needed and used to produce on demand. Feb.2021: in Phase 3 trials. (UK says it will buy 50m doses if approved.)
• Vaxart, US: In early stages of developing a vaccine in pill form that could be distributed by post. Weakened human adenovirus (Ad5) loaded with genes from the coronavirus for both spike and shell. Designed to break down in the small intestine. Feb.2021: Phase 1 study shows it elicits response from T-cells in bloodstream and antibodies in nasal lining but no antibodies in bloodstream. 
• CanSino Biologics, China: A vaccine similar to the Oxford/Astra-Zeneca one. Feb.2021: in Phase 3 trials, which include 30 children aged 6 and 12 given two shots.
• GCVI, global initiative: Vital part of spike protein grown in transgenic yeast and mixed with an adjuvant. This type of vaccine has a good track record, and is similar to a common hepatitis B vaccine. Such vaccines cost about $3 for two doses, and is likely to be suitable for children. Feb.2021: in Phase 2 trials in India. GCVI will seek emergency authorisation in India within months and is negotiating with manufacturers in Africa, Latin America and the Middle East.

Sources: Various.