How Scientists Know The Approved COVID-19 Vaccines Are Safe

After a year which resulted in over 1.7 million deaths and multiple lockdowns, many people are welcoming the news that COVID-19 vaccines are starting to be given to the public. 

How Scientists Know The Approved COVID-19 Vaccines Are Safe

Widespread vaccination may mean that life can return to pre-pandemic normality, however this scenario depends on people’s willingness to get the jab.

Some people are concerned about the safety of vaccines in general, whilst others are suspicious of the novelty and rapid turn-around time of COVID vaccines in particular. We asked 14 experts in immunology, biostatistics and vaccinology whether the COVID-19 vaccines are safe.

Which COVID-19 vaccines have been approved and what does that mean?

Vaccines, along with all other medications, are not allowed to be used until a country ‘approves’ them. This approval process is carried out in each country or group of countries by an independent agency.

In the USA this is done by the FDA (Food and Drug Administration), in the UK by the MHRA (Medicines and Healthcare products Regulatory Agency) and in the European Union the EMA (European Medicines Agency).

In order for anything to be approved by these agencies, it has to show that it is 1) safe and 2) does what it is meant to do.

There are numerous COVID-19 vaccines currently undergoing research and development. Although some of these are already being used in Russia and China, only two vaccines are currently approved for use in the USA and Canada.

One is a joint effort from Pfizer and BioNTech called ‘BNT162b2’ and one is manufactured by Moderna and called ‘mRNA-1273’. BNT162b2 has been approved in 9 countries worldwide, including the UK, and it is also authorised by the EMA.

How does a vaccine get approved?

In order for the Pfizer and Moderna vaccines to be approved by the agencies mentioned above, they must have proved themselves safe. The safety data that is scrutinised during the approval process covers every step of the vaccine’s journey, from the initial experiments in the lab to the manufacturing process.

An important part of this data is the clinical trials. All drugs, including vaccines, pass through three clinical trial stages:

  • Stage I ~ test the vaccine on a small group of volunteers (20-80) to check its safe and find the right dose
  • Stage II ~ find out if the vaccine actually works by dividing 100-300 volunteers into two groups and giving one group the vaccine and the other group a placebo.
  • Stage III ~ divide thousands of volunteers into a vaccine group and a placebo group randomly. Don’t tell the volunteers or the doctors who is in which group (this is called making the trial ‘double-blind’) and check if the vaccine is working and if there are any side effects.

If a trial is not successful, for example the results show that the vaccine is not actually preventing the disease or its causing adverse side effects, the trial is stopped, and the vaccine is not approved.

Even once the vaccine has been approved, it then passes onto Phase IV, where it continues to be monitored and information is collected on adverse effects. This is important to establish whether there are very rare effects, for example at a 1 in 100,000,000 chance.

For example, two people in the UK had an allergic reaction to the Pfizer vaccine after it was given to thousands. This sometimes happens in response to flu vaccines as well, and healthcare workers are ready to handle such reactions when they give the jab.

Both people have fully recovered, but collecting information on this is useful , for example the UK has now issued precautionary advice to people who have severe allergies.

Dr Olivera Finn from the University of Pittsburgh explains that “All new vaccines continue to be monitored once they begin to be widely distributed. We are now well connected with the whole world so a single problem with the vaccine anywhere in the world will prompt quick examination and changes if warranted.”

What safety data are there?

Both the Pfizer and Moderna vaccines have undergone all three clinical trials and not found any serious side effects from their vaccines.

For the Pfizer vaccine, 195 people were recruited in the USA-based Phase I trial and 456 were included in the Germany-based Phase II trial. In both trials, nobody who received the vaccine had any serious side effects. Pfizer’s Phase III trial has been published in a peer-reviewed journal and included over 40,000 volunteers in 152 sites worldwide.

In this trial, volunteers were divided into two groups. One group was given two placebo jabs 21 days apart, and one group the actual vaccine jabs. This means that in the end 18,566 people received the full 2 doses of the vaccine.

For 14 weeks after the second jab all 18,366 volunteers were assessed for side effects, both by surveys and taking blood samples. After the second jab, only 0.8 percent of them got a fever. More common symptoms were soreness at the injection site and sometimes sore muscles and headaches.

Professor Rick Kennedy from the Mayo Clinic explains that “the vast majority of the side effects seen were expected and are a direct result of the immune response to the vaccine. Side effects are similar to what has been seen with most other licensed vaccines and ore occurring at similar rates and with similar levels of severity (mostly mild and moderate).” No one in the study had a severe reaction to the vaccine.

An important factor is that this Phase III study included people from diverse backgrounds: 49 percent were female and 37 percent were black, African-American or Hispanic.

On top of this, the study included people who may be at a higher risk level: 35 percent of participants were obese, 21 percent had at least one coexisting condition and the median age of the volunteers was 52.

The Moderna vaccine similarly included 120 people in their Phase I trial and 600 people in their Phase II trial. Although not all the data from the Phase III are available for the public yet (the approving agencies are given access), it included 30,000 people of diverse demographics and has not seen any severe side effects.

All of the above information is freely available for anyone to read. On top of this, the regulatory agencies that approved these two vaccines had access to much more data that cover not only the clinical trials but lab and animal studies. This information is often more than 10,000 pages long and is carefully examined by the FDA, MHRA and EMA.

What is in the COVID vaccines?

Both Moderna and Pfizer’s vaccines are RNA vaccines. RNA is the information inside the SARS-CoV-2 virus which codes for all the virus’ machinery.

Traditional vaccines use a dead or modified version of the virus to cause the body to create an immune response, so it learns to recognise this virus and therefore becomes immune to it. RNA vaccines use a modified version of the SARS-CoV-2 virus RNA instead.

When the RNA gets into your cells, your cells make their own virus fragments, which then teach your body to become immune like any other vaccine. RNA in itself is not harmful, in fact your cells make and use RNA all the time.

As Professor Crotty from the La Jolle Institute for immunology explains “At any moment a human cell has 5,000+ different RNA messages, and they are all temporary messages, like post-it notes that get torn up by the cells within minutes or hours after being read.”

The RNA from the vaccine is broken down within a day of injection. Importantly, the vaccines only contain a small section of the RNA, “the RNA message is for one single coronavirus protein. It takes 25 different coronavirus proteins to make a coronavirus, so there is no worry about the RNA making a virus.”

The RNA is packaged in tiny balls of fats called lipid nanoparticles. These lipids are broken down and eliminated by your cells. The other ingredients are water and some salts and sugars to keep these particles stable.

This technology of delivering RNAs by lipid nanoparticles has not been used for vaccines before. However, medicines that use lipid nanoparticles (called ‘nanomedicines’) have been in use since the 1990s, and to date over 20 different ones have been approved by the FDA or EMA. Some of these medicines are RNA-based, similar to the RNA vaccines. They are usually used for cancer and gene therapies.

How come the vaccines were made so quickly?

Usually, vaccines take years to be developed and produced. The COVID-19 vaccines took less than one year. This is due to a number of reasons, three of which are explained by Dr Robert Carnahan from the Vanderbilt University Medical Centre:

“One, all of the vaccines … were manufactured ‘at risk’. This means that they were being produced before the clinical trials were even completed. This would never happen in a normal situation. Many of these costs were supported by various government organizations around the globe. Therefore, the instant that emergency approval was secured, the distribution could begin.

Second, vaccine developers were rapidly analyzing data as they emerged and communicating this in real-time to various regulatory agencies. There are often gaps of months to years between the various phases of clinical trials due to these activities alone.

Third, recruitment to clinical trials is often a slow and laborious process. There have to be people ‘at-risk’ for the disease in many different demographic and health categories. Due to the immense scope of the pandemic, finding sufficient and appropriate volunteers was rapid.”

Importantly, the speed did not affect the clinical trials and safety aspects of the process: “The size, thoroughness, and complexity of the clinical trials conducted for the current COVID-19 vaccines were no different than traditional clinical trials. These are as safe as vaccines and interventions developed on much slower timelines.” – Dr Carnahan says.

A balance of risk

Nothing in medicine is 100 percent safe – you don’t take medication for a disease you don’t have or a vaccine against a disease that doesn’t exist.

Dr William Hausdorff from PATH, a global nonprofit public health organisation, explains that “all discussions of ‘safety’ for vaccines (or medicines in general) have to start with discussions of how serious and frequent is the condition you are trying to prevent or treat. 

If the condition is very minor, then even trivial side effects may be not worth it. If the condition is very serious, then people will accept much bigger potential side effects”.

Every medical intervention is a balance of risk vs benefit. Both the Pfizer and Moderna vaccines have shown >90 percent efficacy at protecting people from COVID-19 in their Phase III clinical trials. This protection from a virus which has so far caused over 1.7 million deaths globally is also an important consideration when thinking about vaccine safety.

The Takeaway

All 14 experts agreed with the scientific consensus that the COVID vaccines that have been approved by the proper regulatory agencies such as the FDA are as safe as any other vaccine or medication.

Nothing in medicine is risk-free and the decision to take a vaccine is personal and dependent on a person’s individual circumstances. 

Originally published at Science alert