23andMe : Felt Ill After COVID-19 Vaccine? It May Depend on Which Vaccine and Whether You’ve Had COVID-19

These relationships between sex, age, and vaccine reaction held up, even after controlling for potential confounders.

How do the COVID-19 vaccines work?

The COVID vaccines teach your immune system to recognize and respond to the virus that causes COVID-19. The vaccines introduce genetic instructions to make a harmless protein that is unique to the virus. This triggers a two-step immune response: a first, more immediate and non-specific reaction (the innate immune response), followed by a more gradual, pathogen-specific reaction (the adaptive immune response).⁶

But why do some people feel very sick from their COVID-19 vaccine, and others don't feel sick at all? Scientists aren't quite sure why that is. However, data points to the immune system.

What does my vaccine reaction mean?

Trends identified in 23andMe data support what the vaccine clinical trials and other studies have observed -that there are certain groups of people who are more likely to have felt sicker from their COVID-19 vaccination. These include:

• Women⁷
• Younger people^7,8,9,10
• Recipients of a second dose vaccine (compared to their first dose)^8,9,11

Women, for instance, seem to have stronger immune reactions than men. Research for other types of vaccinations, such as for influenza, yellow fever, and hepatitis, showed that women produce more infection-fighting antibodies than men following vaccination.¹²Hormonal and genetic differences between the sexes may also play a role in how the immune systems of men and women respond differently to vaccinations.^12,13

As we age, our immune systems tend to weaken.¹⁴This may explain why younger adults were generally more likely to report a larger number of and more severe symptoms following their vaccination compared to older adults, as seen in data from 23andMe consented research participants and elsewhere, including the vaccines' clinical trials.^7,8,9,10

By the time you receive a second dose, your body has already become primed to recognize and respond to the virus that causes COVID-19, and as a result your immune system responds faster and stronger.^15,16This likely explains why people tend to have more severe reactions to their second dose compared to their first dose.

And it may also be why 23andMe researchers observe that people with a history of COVID-19 infection also feel more ill following their most recent vaccination, compared to those without a prior infection. The virus itself is an additional trigger for your immune responses to kick in. Several small studies have found that people with a history of COVID-19 infection experienced symptoms more frequently^17,18and had higher levels of antibodies after a first dose,¹⁹compared to those without a history of infection.

This analysis on over 100,000 individuals builds upon these findings, showing that a previous COVID-19 infection might not just be related to the number of symptoms experienced following a COVID-19 vaccination, but also the severity of these symptoms.

The COVID-19 vaccines are still effective, regardless of your vaccine-related reaction

Although there is some uncertainty regarding why some people experience more mild or severe symptoms following their COVID-19 vaccination, what we do know is this: the COVID-19 vaccines are effective, whether or not you felt sick after the vaccination.

Data from the vaccine trials showed that not everyone reported vaccine-related reactions; 23% from Pfizer, 18% from Moderna (second dose), and between 39% (younger adults) and 55% (older adults) from J&J didn't experience any systemic reactions.^8,9,10And this is coming from the same data that demonstrated how safe and effective these vaccines are.

Put another way: 'Even if you don't have an unpleasant reaction, the vaccines are still doing their job, because the real work of the immune system - and of the vaccines - takes place during the second, or adaptive phase of the immune response.'¹⁶

What's next?

Research is ongoing to understand why reactions to the COVID-19 vaccines differ and what these differences mean. This work is part of our ongoing broad research into COVID-19 that has included studying how genetics plays a role in both thesusceptibility and severity of COVID-19, and looking at other aspects of the pandemic like its impact onsleep,physical activityand how it hashit some communities harder than others. As part of this work our, scientists are preparing to run genetic analyses to help answer why individuals react differently to the vaccine and what those differences might mean.

*The 23andMe COVID-19 research team includes: Adam Auton, Adrian Chubb, Alison Fitch, Alison Kung, Amanda Altman, Andy Kill, Anjali Shastri, Antony Symons, Catherine Weldon, Chelsea Ye, Jason Tan, Jeff Pollard, Jey McCreight, Jess Bielenberg, John Matthews, Johnny Lee, Lindsey Tran, Maya Lowe, Michelle Agee, Monica Royce, Nate Tang, Pooja Gandhi, Raffaello d'Amore, Ruth Tennen, Scott Dvorak, Scott Hadly, Stella Aslibekyan, Sungmin Park, Taylor Morrow, Teresa Filshtein Sonmez, Trung Le, and Yiwen Zheng.