SINGAPORE - The most common side effect experienced among those who have received a Covid-19 vaccine has been soreness around the injection site.

This was also more frequent among younger vaccine recipients, with 83 per cent of those between 18 and 55 reporting sore arms after receiving the first jab, noted a Pfizer-BioNTech vaccine clinical trial. This compared with 71 per cent of those aged above 55.

Similarly, 87 per cent of people under the age of 65 reported localised pain after the first shot of the Moderna vaccine during clinical trials, compared with 74 per cent of those over 65.

The Straits Times looks at why the side effects vary between different groups of people.

Q: Why does my arm hurt after taking the vaccine and why are side effects worse after the second dose?

A: Professor Ooi Eng Eong from the Duke-NUS Medical School said the commonly reported side effects of the mRNA Covid-19 vaccines are largely caused by the body's immune response. These are pain at the injection site, tiredness, headache and body aches.

"For instance, the pain at the injection site is caused not only by the insertion of a hypodermic needle, but also by immune cells infiltrating the injection site to 'pick up' the vaccine," he said.

"Moreover, activated immune cells would 'talk' to other immune cells to coordinate their response through chemicals, which causes the... side effects."

This explains why more people experience side effects after the second dose than the first, as the first jab primes the immune system to the Sars-CoV-2 spike protein. So the immune response to the second dose is likely to be more robust than the first, said Prof Ooi.

Dr Tseng Hsien Cho, physician lead at Raffles Medical Group, said the immune system has two layers of response - the innate immune response followed by the adaptive immune response.

"The innate immune response is activated as soon as our body detects any foreign material, from a speck of dust to a virus. The goal is to identify and eliminate the foreign substance with specialised white blood cells known as neutrophils and macrophages," he added.

This form of inflammatory response explains the aches and pains after receiving the first jab, said Dr Tseng, and this usually lasts for only a few hours or days.

It is the adaptive immune response - the second layer of immune defence - that takes days or weeks to develop.

"This is when the immune system's T-cells and B-cells learn to recognise specific invaders, such as proteins from the Sars-CoV-2 virus."

This time, the immune memory generated is a long-lasting one, such that if the body encounters the same viral protein in future, the immune cells will be able to recognise the invaders and start generating antibodies for defence.

Q: Why do younger people experience more side effects compared with older people?

A: Prof Ooi said the robustness of the body's immune response to the vaccine can explain why the incidence of side effects differs depending on age.

Health Sciences Authority data has shown that about 0.13 per cent of the doses administered resulted in suspected adverse reactions, with younger people more likely to experience side effects.

"Like the rest of our body, the immune system ages. Younger individuals react more robustly to vaccines than older individuals," said Prof Ooi.

However, he noted that it is unclear whether the side effects are caused by the immune response to the spike gene or protein encoded in the vaccine, or due to other components in the vaccine formulation.

Professor Paul Tambyah, president of the Asia-Pacific Society of Clinical Microbiology and Infection, said that while it is possible for the side effects to be "immune-mediated reactions", there is no data on exactly how this occurs.

For instance, one of the common side effects - facial swelling - is related to the release of a protein by various kinds of cells and can be in response to an allergen or some types of medications, he added.

Q: How do the side effects of the Pfizer and Moderna vaccines compare with those of other types of Covid-19 vaccines?

A: Dr Tseng said there has been a higher incidence of allergies linked to mRNA vaccines than non-mRNA vaccines.

This is because the mRNA component in the vaccine is wrapped in a bubble of lipids with polyethylene glycol, which is a compound that could trigger allergic responses, he said.

However, Prof Tambyah said there is a need to carefully scrutinise the data from various health authorities to determine the range of side effects for different vaccines.

For instance, he pointed out that in the clinical trials of the mRNA vaccines, Bell's Palsy, which causes temporary weakness or paralysis of facial muscles, occurred more commonly in subjects who received the vaccine versus those who received a placebo.