What’s behind the common COVID-19 vaccine side effects?

Garvan immunologist Professor Jonathan Sprent explains why you should feel good about the common COVID-19 vaccine side effects, such as headache, fatigue and muscle pain.

Professor Jonathan Sprent

07 July 2021

After receiving a COVID-19 vaccine, many experience mild yet common symptoms, such as headache, fatigue and muscle pain – side effects reported by more than 100,000 Australians to date in a national survey.

These vaccine side effects have led to hesitancy in some younger people, who may have more symptoms following a COVID-19 vaccine than during an infection with coronavirus itself, says immunologist Professor Jonathan Sprent who heads the Cellular Immunity Lab at the Garvan Institute of Medical Research.

“However, these common post-vaccine side effects, such as headache, fatigue and muscle pain, are a reassuring sign that the immune system is doing its job in responding to the vaccine. They signal type I interferon production – the body’s in-built immune stimulator that elicits a powerful immune response to eliminate the pathogen and also generates memory immune cells that protect against re-infection.”

A recent Science Immunology article, co-authored by Professor Sprent, delves into the science behind common COVID-19 vaccine side effects and explains why they should be viewed positively – a necessary prelude to an effective immune response.

Interferon – a first responder with lasting protection

During an infection with a viral pathogen, the immune system jumps into action. A crucial part of this response is the immune molecule interferon. Named for its ability to ‘interfere’ with virus replication, interferon rapidly signals cells to heighten their defences and prevent viruses from replicating in human cells.

“Interferon then begins to act on immune cells, causing B cells to expand and produce specific antibodies that enter the bloodstream to inactivate the virus. At the same time interferon stimulates T cells to destroy cells that have ingested the virus,” says Professor Sprent.

“Together the combined attack by these two types of immune cells eliminates the pathogen quite quickly. Meanwhile, interferon stimulates some of the specific T and B cells generated during the initial infection to survive and form long-lived memory cells, which provide long-term protection against a second encounter with the same pathogen.”

Although direct evidence is still lacking, it is highly likely that the side effects of COVID-19 vaccines are simply a reflection of strong interferon production, says Professor Sprent. In fact, therapeutic injection of interferon, which is currently used to treat hepatitis B and hepatitis C infections and multiple sclerosis, is known to induce the same side effects as COVID-19 vaccines.

How interferon elicits these side effects is unclear, he adds, but they are likely a manifestation of interferon’s ability to stimulate production of multiple cytokines, molecules that activate various components of the immune response.

Blocking interferon – a COVID-19 survival strategy

Some people with severe COVID-19 have autoantibodies – antibodies that attack a person’s own cells or proteins – that target interferon and effectively block its action in the body, explains Professor Sprent. In addition, certain components of the virus can physically block interferon.

“This may be one of the coronavirus’s survival strategies – by suppressing interferon production, it stops people from feeling sick while allowing virus replication. This means that people are more likely to be in the community, spreading the virus on to others.”

But COVID-19 vaccines get around this problem, he adds.

“Most COVID-19 vaccines rely on production of the spike protein of SARS-CoV-2, which doesn’t block interferon and is therefore able to elicit an effective immune response – crucial for providing protection against re-infection the next time the virus comes around.”

“This difference means that young people, who are more often asymptomatic during COVID-19 infection, may have stronger side effects to the vaccine than to the virus itself. Younger people and women naturally make more interferon, and they are also the group which has the most side effects to the COVID-19 vaccine,” says Professor Sprent.

“It should be noted however, that the side effects of vaccination will nearly always be mild and transient, and indicate merely that the vaccine is doing its job of stimulating production of interferon and providing us with crucial protection against COVID-19.”

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