Among the talks and presentations at the <a href="https://www.ashg.org/meetings/2023meeting/">annual meeting of the American Society of Human Genetics</a> during the first week of November in Washington D.C. will be two poster presentations by 23andMe scientists on new genetic findings around COVID and long COVID.



The poster presentations are part of a collection of presentations, panel discussions, and talks by scientists from 23andMe at this year’s conference.&nbsp;



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="1024" height="477" src="http://35.88.189.111/wp-content/uploads/2021/12/COVID-Image-1024x477.png" alt="A logo for 23andMe's COVID-19 Research Study" class="wp-image-29418" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image-1024x477.png 1024w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image-300x140.png 300w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image-768x358.png 768w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image-880x410.png 880w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image-1180x550.png 1180w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/12/COVID-Image.png 1394w" sizes="auto, (max-width: 1024px) 100vw, 1024px" /></figure>



23andMe’s Vice President of Genomic Health, Noura Abul-Husn, M.D. Ph.D. will be on a panel focused on returning genetic results to consumers. 23andMe senior research project manager Anjali Shashtri, Ph. D., will talk on a separate panel about 23andMe’s efforts in building trust and research participation within underrepresented populations.



ASHG expects more than 8,000 researchers and clinicians at this year’s meeting, where they&#8217;ll share emerging discoveries and new genetic research.&nbsp;



“Human genetics is transforming science and health at a rapid pace, and ASHG’s 75th anniversary Annual Meeting provides both a milestone in the history of human genetics and genomics and a moment to look to a future in which genetics research improves the health and wellbeing of people everywhere,” said ASHG President Brendan Lee, MD, PhD. “Thousands of our members from across the globe will join to network, share discoveries, and explore new ways to apply genetics knowledge.”



<h6 class="wp-block-heading" id="h-23andme-covid-research">23andMe COVID Research</h6>



The two COVID presentations highlight include data on novel genetic variants associated with long COVID and other variants associated with COVID and having the symptom of diarrhea. Other studies have shown that having diarrhea may prolong the time it takes to clear the virus from their bodies, increasing the chances of more severe symptoms.



The two studies are part of ongoing COVID research 23andMe began soon after the pandemic emerged in 2020.&nbsp;



The work has revealed new insights on <a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/">the role blood type plays</a> in severity and susceptibility to the virus, as well as insights into the genetics that influence <a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/">different reactions</a> to COVID-19 vaccines. In early 2022, 23andMe published a study in<a href="https://www.nature.com/articles/s41588-021-00986-w"> Nature Genetics</a> that identified genetic variants associated with the loss of smell or taste due to COVID-19. That paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.



<h6 class="wp-block-heading" id="h-long-covid">Long COVID</h6>



The work presented this year at ASHG includes data on novel variants associated with long COVID. The variants are in genes within the human leukocyte antigen (HLA) complex related to immune response. Studies previously revealed an association of one of the variants with COPD, another with an allergic response, and a third with a response to viral infection.&nbsp;



The new data may help as researchers are still trying to determine why some people with COVID develop long COVID. Estimates suggest that between 12 -to- 16 percent of people with COVID will develop long COVID. The risk of long COVID is much higher among COVID patients with symptoms that are serious enough to require hospitalization.&nbsp;&nbsp;



One of the largest of its kind, this study included data from 140,000 23andMe customers who consented to participate in research, 41,000 of whom had long COVID.&nbsp;



The study also confirmed some previous findings and found novel genetic variants associated with long COVID. Among those were that females were likelier to develop long COVID than males. Individuals with long COVID are also more likely to have had depression, smoked cigarettes, or have had high blood pressure than those who do not develop long COVID. In addition, the researchers found genetic correlations between long COVID and conditions such as chronic fatigue, fibromyalgia, chronic pain, and depression.



<h6 class="wp-block-heading" id="h-covid-and-diarrhea">COVID and Diarrhea</h6>



23andMe’s second COVID-related presentation at the ASHG conference includes new genetic findings about individuals with COVID who also experience diarrhea. The study included data from about 140,000 people with COVID who also consented to participate in 23andMe’s research; of that total, about 80,000 reported having diarrhea as a symptom of COVID.



The researchers found several novel genetic variants associated with diarrhea and COVID-19. The strongest association was in the gene CYP7A1, associated with lipid function and cholesterol levels. Researchers also found an association with a variant in the gene CCR9, which was previously associated with susceptibility to COVID. Another variant associated with diarrhea among those with COVID was a variant in the gene GCKR, which is associated with fasting plasma glucose and chronic kidney disease.



<h6 class="wp-block-heading" id="h-23andme-other-research-presentations">23andMe Other Research Presentations</h6>



The conference will include a broad range of research across the field of genomics.&nbsp;



Along with the presentations on COVID and long COVID and panel discussions, 23andMe scientists will also be presenting some of our latest research on using polygenic risk scores to make earlier diagnoses of diabetes, evaluating the contributions of both rare and common variants in disease risk, and details from the study on the genetic legacy of African Americans from the Catoctin Furnace.&nbsp;



<hr class="wp-block-separator has-alpha-channel-opacity"/>



<figure class="wp-block-image aligncenter size-full"><img loading="lazy" decoding="async" width="174" height="87" src="http://35.88.189.111/wp-content/uploads/2023/10/ASHG-logo-75anniversary.png" alt="" class="wp-image-32283"/></figure>



<h6 class="wp-block-heading" id="h-23andme-s-presentations-amp-panels">23andMe&#8217;s Presentations &amp; Panels</h6>



<ul class="wp-block-list">
<li>Noura Abul-Husn, M.D. Ph.D., 23andMe Vice President of Genomic Health </li>



<li>Presenter: “Returning genomic results to consumers: The DTC approach”</li>



<li>Sat, Nov 4 8:50 &#8211; 9:05 am (ET) </li>



<li>Conv Ctr/Ballroom C/Level 3 </li>



<li>Presenter 04</li>
</ul>



<ul class="wp-block-list">
<li>Noura Abul-Husn, M.D. Ph.D., 23andMe Vice President of Genomic Health </li>



<li>Panelist: “Advancing Global Data Sharing and Complex Considerations” </li>



<li>Fri, Nov 3 3:00 &#8211; 4:15 pm (ET) </li>



<li>Conv Ctr/Room 152AB/Level 1</li>
</ul>



<ul class="wp-block-list">
<li>Anjali Shastri, Ph.D., 23andMe Senior Research Project Manager</li>



<li>Presenter: “Lessons learned in building trust and engaging underrepresented groups in direct-to-consumer genetic testing” </li>



<li>Sat, Nov 4 1:45 &#8211; 2:00 pm (ET) </li>



<li>Conv Ctr/Room 202A/Level 2</li>



<li>Presenter 06</li>
</ul>



<ul class="wp-block-list">
<li>Amy Sturm, Ph.D., 23andMe Director, Population Health Genomics</li>



<li>Session Co-Moderator “Harnessing return of value: Progress in returning genomic results to individuals in diverse, large-scale programs” </li>



<li>Sat, Nov 4 8:30 &#8211; 10:00 am (ET) </li>



<li>Conv Ctr/Ballroom C/Level 3 </li>



<li>Session 92</li>
</ul>



<h6 class="wp-block-heading" id="h-posters">Posters</h6>



<ul class="wp-block-list">
<li>Stella Aslibekyan, PhD, 23andMe Principal Scientist, Genetic Epidemiology </li>



<li>Poster: “Multi-ancestry analysis of COVID-19+ diarrhea reveals genetic associations with lipid function: a 23andMe Research Study” </li>



<li>Thu, Nov 2 3:00 &#8211; 5:00 pm (ET) </li>



<li>Board number 4160 </li>



<li>Presenter 054</li>
</ul>



<ul class="wp-block-list">
<li>Ninad S. Chaudhary, PhD,&nbsp; 23andMe Postdoctoral Fellow, Genetic Epidemiology </li>



<li>Poster: “Genetic architecture of Long COVID indicates associations with immune function, and shared etiology with chronic conditions in European population” </li>



<li>Thu, Nov 02 3:00pm &#8211; 5:00pm (ET) </li>



<li>Board number 1666 </li>



<li>Presenter 121</li>
</ul>



<ul class="wp-block-list">
<li>Zachary Fuller, PhD, 23andMe Scientist II, Statistical Geneticist </li>



<li>Poster: “Evaluating the contributions of rare and common variants in disease risk” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4137 </li>



<li>Presenter 47</li>
</ul>



<ul class="wp-block-list">
<li>Chris Germain, PhD, 23andMe Scientist I, Statistical Geneticist &amp; Machine Learning&nbsp;</li>



<li>Poster: “Polygenic risk and early diagnosis of diabetes” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4323 </li>



<li>Presenter 109</li>
</ul>



<ul class="wp-block-list">
<li>Éadaoin Harney, PhD, 23andMe Scientist I, Population Genetics R&amp;D&nbsp;</li>



<li>Poster: “The genetic legacy of African Americans from Catoctin Furnace”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 3122</li>



<li>Presenter 122</li>
</ul>



<ul class="wp-block-list">
<li>Sarah Laskey, PhD, 23andMe Senior Scientist, Health R&amp;D&nbsp;</li>



<li>Poster: “Absolute and relative contextualization of polygenic scores in genetically diverse and admixed populations” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4338 </li>



<li>Presenter 114</li>
</ul>



<ul class="wp-block-list">
<li>Yanyu Liang, PhD, 23andMe Scientist I, Statistical Geneticist&nbsp;</li>



<li>Poster: “Credible set is sensitive to imputation quality and missing variants”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4107</li>



<li>Presenter 037</li>
</ul>



<ul class="wp-block-list">
<li>Shubham Saini, PhD, 23andMe Scientist I, Statistical Geneticist&nbsp; </li>



<li>Poster: “Population Scale Analysis of Copy Number Variation in 23andMe Research Cohort” </li>



<li>Fri, Nov 3; 3:00-5:00 pm ET </li>



<li>Board number 4326 </li>



<li>Presenter 110</li>
</ul>



<ul class="wp-block-list">
<li>Jingchunzi Shi, PhD, 23andMe Senior Scientist I, Genomics R&amp;D </li>



<li>Poster: “Evaluating genetically-predicted causal effects of lipoprotein(a) in human diseases: a phenome-wide Mendelian randomization study”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4136</li>



<li>Presenter 046</li>
</ul>



<ul class="wp-block-list">
<li>Wei Wang, PhD, 23andMe Senior Scientist I, Statistical Genetics</li>



<li>Poster: “A polygenic risk score of postoperative nausea and vomiting improves risk prediction and shows genetic correlation with CNS conditions including vertigo and motion sickness”</li>



<li>Fri, Nov 3; 3:00-5:00 pm ET</li>



<li>Board number 4209</li>



<li>Presenter 010</li>
</ul>



<ul class="wp-block-list">
<li>Amy Williams, PhD, 23andMe Senior Scientist II, Product R&amp;D </li>



<li>Poster: “Reconstructing parent genotypes at direct testing-level accuracy using siblings and other relatives.” </li>



<li>Thurs, Nov 2; 3:00-5:00 pm ET </li>



<li>Board number 3106 </li>



<li>Presenter 106</li>
</ul>



You can find out more about this year’s ASHG meeting <a href="https://www.ashg.org/meetings/2023meeting/">here</a>.

A logo for 23andMe's COVID-19 Research Study

23andMe to Present New COVID Data at ASHG Conference

In early March 2020, the World Health Organization declared we were in the middle of a worldwide pandemic. Three years later, and few things are left untouched by the COVID-19 virus. Almost seven million people worldwide have died, and untold millions are still struggling with long COVID. Yet, looking at all that has happened and continues to transpire, there is much to glean from this experience.



<figure class="wp-block-image size-large"><img loading="lazy" decoding="async" width="914" height="1024" src="http://35.88.189.111/wp-content/uploads/2022/02/COVID-Study-Graphic-914x1024.jpg" alt="" class="wp-image-29489" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2022/02/COVID-Study-Graphic-914x1024.jpg 914w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2022/02/COVID-Study-Graphic-268x300.jpg 268w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2022/02/COVID-Study-Graphic-768x861.jpg 768w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2022/02/COVID-Study-Graphic-785x880.jpg 785w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2022/02/COVID-Study-Graphic.jpg 1026w" sizes="auto, (max-width: 914px) 100vw, 914px" /><figcaption class="wp-element-caption">A run-down of COVID-19 research during the first months of the pandemic.</figcaption></figure>



Others are looking at the public health response, public policy, questions about the virus&#8217;s origin and other issues that are very important. But we here at 23andMe want to look at the science, or at least what we learned through our ongoing research of COVID-19.



<h6 class="wp-block-heading" id="h-the-covid-19-study">The COVID-19 Study</h6>



So, how has 23andMe contributed to COVID-19 research?



When the pandemic emerged, our scientists, like others worldwide, asked what we could do to help. 23andMe has a research platform that leverages one of the largest genetic and phenotypic databases of consented research participants to generate genetic insights at unprecedented speed. So back in March 2020, we decided to leverage this tool to learn as much as possible about the virus and share it as rapidly as possible with others. That&#8217;s how we began our <a href="https://you.23andme.com/covid19-study/">COVID-19 study</a>.



We launched in March 2020, asking our customers who have consented to participate in research about their own experience with the virus. In a matter of a few months, we had more than 1.2 million people participating in our study, and we were able to generate a host of insights. By June, we shared our first finding — that <a href="https://blog.23andme.com/23andme-research/blood-type-and-covid-19/" target="_blank" rel="noreferrer noopener">blood type</a> could play a role in the susceptibility of the virus. In addition, we identified a locus on chromosome 3 that could influence the severity in symptoms among those who get it.



In less than 90 days, we were able to analyze results and share them with other scientists, offering insights into the nature of the virus and why some people may be more susceptible or have a more severe reaction than others. We published the findings on a preprint server in September and later in <a href="https://www.nature.com/articles/s41588-021-00854-7" target="_blank" rel="noreferrer noopener">Nature Genetics</a>.



<figure class="wp-block-image size-full"><img loading="lazy" decoding="async" width="675" height="711" src="http://35.88.189.111/wp-content/uploads/2013/04/Empty-Bed.jpg" alt="An empty bed." class="wp-image-17852" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2013/04/Empty-Bed.jpg 675w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2013/04/Empty-Bed-285x300.jpg 285w" sizes="auto, (max-width: 675px) 100vw, 675px" /></figure>



<h6 class="wp-block-heading">Taste, Smell, Anxiety, and Sleep</h6>



We found other genetic insights, including genetic associations with the loss of <a href="https://blog.23andme.com/23andme-research/loss-of-smell-covid-study/" target="_blank" rel="noreferrer noopener">smell and taste</a>, a common symptom among those with the virus. This information could indicate how the coronavirus SARS-CoV-2 enters the body and accumulates in the olfactory cells of those infected.



23andMe scientists also looked at <a href="https://blog.23andme.com/23andme-research/covid-19-vaccine-reactions/" target="_blank" rel="noreferrer noopener">vaccine reactions</a>. We learned that the second in the two-dose Moderna vaccine produced the strongest response, and we found that younger people and women tended to have a stronger reaction to the vaccine.



We also garnered insight into the vaccine’s impact on underrepresented populations. Because 23andMe has so many individuals from traditionally underrepresented populations, our scientists were able to look at how the virus impacted people of <a href="https://blog.23andme.com/23andme-research/impact-disparities-of-covid-19/" target="_blank" rel="noreferrer noopener">different ethnicities</a>.



We did other non-genetic studies looking more broadly at how the pandemic, <a href="https://blog.23andme.com/articles/social-distancing-and-covid-19" target="_blank" rel="noreferrer noopener">social distancing</a> guidelines, and other public health responses were impacting people&#8217;s <a href="https://blog.23andme.com/articles/covid-impact-on-sleep">sleep</a> <a href="https://blog.23andme.com/articles/activity-changes-during-covid" target="_blank" rel="noreferrer noopener">and activity levels</a>. 



<h6 class="wp-block-heading">Long COVID</h6>



More recently, we&#8217;ve looked at how <a href="https://blog.23andme.com/articles/anxiety-long-covid" target="_blank" rel="noreferrer noopener">depression and anxiety</a> significantly increase the risk for <a href="https://blog.23andme.com/articles/anxiety-depression-long-covid" target="_blank" rel="noreferrer noopener">Long COVID</a>. Ours was one of the largest studies of long COVID at the time and confirmed that long COVID disproportionately impacts women.  



In three years, we learned a lot. But we still need to learn more, particularly about the long-term implications of having had the virus, and long COVID itself.



We&#8217;re now focused on long COVID, trying to understand why it impacts women more than men. We&#8217;re also looking at an apparent association with cardiometabolic diseases, such as <a href="https://www.23andme.com/topics/health-predispositions/high-blood-pressure/" target="_blank" rel="noreferrer noopener">high blood pressure</a>, <a href="https://www.23andme.com/topics/health-predispositions/coronary-artery-disease/" target="_blank" rel="noreferrer noopener">coronary artery disease,</a> <a href="https://www.23andme.com/topics/health-predispositions/type-2-diabetes/" target="_blank" rel="noreferrer noopener">type 2 diabetes</a>, and <a href="https://www.23andme.com/topics/health-predispositions/ldl-cholesterol/" target="_blank" rel="noreferrer noopener">high cholesterol</a>.



As new insights into COVID-19 arise, we’ll be sure to share them.

COVID-19 Three Years In 

Despite a lingering pandemic, most people in the US say they feel less stressed or anxious this year compared to earlier in the pandemic, according to a new survey by 23andMe.



In this third holiday under the shadow of COVID-19, people appear to have adjusted to the new normal and are more optimistic about their health. Many have returned to their traditional holiday celebrations, according to the survey.&nbsp;&nbsp;



<h6 class="wp-block-heading" id="h-stress-and-anxiety-remains">Stress and Anxiety remains</h6>



However, about 14 percent say they still feel stressed, and more than 11 percent said they’re anxious about the future. And about 77 percent of those surveyed said they still feel some sort of negativity around their health.



But stress levels have significantly dropped since the beginning of the pandemic, with only about 14 percent of those surveyed saying they were stressed, compared to more than 47 percent in 2020. Similarly, only about 5 percent said they were more depressed this year than last, compared to almost 32 percent in 2020.



Beyond this survey, 23andMe has done extensive research on the genetics of depression and anxiety, which has downstream impacts on health. Anxiety disorders like depression and anxiety are <a href="https://www.nimh.nih.gov/health/statistics/major-depression">very common</a>. Up to three-in-ten people in the U.S. will be diagnosed with one during their lifetime, according to prevalence <a href="https://www.nimh.nih.gov/health/statistics/any-anxiety-disorder">statistics</a> from the National Institute of Mental Health. Researchers believe that genetics combine with other factors to influence how likely an individual is to develop an anxiety disorder.&nbsp;



<h6 class="wp-block-heading">A focus on health</h6>



The survey commissioned by 23andMe and conducted by SurveyMonkey on U.S. adults in early November, found that health is understandably a focus for many people. Almost half of the respondents who said they’re focused on their health also said they planned to make healthy lifestyle changes in the new year with a focus on their diet and weight.



Many of those surveyed said the pandemic had impacted their waistline in the last year, with about 12 percent saying they gained weight.



People are also feeling less isolated this year. Perhaps contributing to that shift in optimism is a renewed connection to family and friends. The percentage of respondents who feel less connected to friends and family dropped from 48 percent in 2020 to just 5 percent in 2022. The survey showed a similar drop in the percentage of people saying they were depressed, going from 32 percent in 2020 to just 5 percent this year.



<h6 class="wp-block-heading">More family bonding this holiday season</h6>



Lockdowns meant that in the first year of the pandemic, most people said they’d canceled family holiday plans, preferring to stay at home. But this year, that has shifted. Only about 17 percent of people said they would not be having a traditional holiday this year, compared to 62 percent in 2020.



More than 40 percent of those surveyed said they’re returning to their traditional holiday plans this year, and one in five people said they never changed their traditional celebration throughout the whole pandemic.



This is in stark contrast to 2020 when 41 percent of those surveyed said they weren&#8217;t traveling for the holidays, and 34 percent said their friends and family also didn’t plan to visit them.

Despite COVID-19 People Less Anxious This Holiday

A new study by researchers at the Harvard T.H. Chan School of Public Health confirms<a href="https://blog.23andme.com/23andme-research/anxiety-depression-long-covid/"> findings from 23andMe</a> that depression and anxiety dramatically increase the likelihood of experiencing long COVID.
Published online in JAMA Psychiatry earlier this month, the<a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796097"> study</a> found that psychological distress in the form of depression, anxiety, stress, and loneliness were more predictive than many physical risk factors like obesity, asthma, and hypertension, said Siwen Wang, the researcher in the Department of Nutrition at Harvard T.H. Chan School who led the study.
“We were surprised by how strongly psychological distress before a COVID-19 infection was associated with an increased risk of long COVID,”<a href="https://www.hsph.harvard.edu/news/press-releases/psychological-distress-before-covid-19-infection-increases-risk-of-long-covid/"> Siwen said.</a>
<h2>Psychological Stress Increases Risk of COVID</h2>
The team’s findings showed that psychological stress contributed to a one-and-a-half-fold increase in the risk for long COVID. 23andMe’s results showed a two-fold increase. But the differences in the two studies may be explained by how the studies defined long COVID. 23andMe looked at data from individuals with a formal diagnosis of long COVID. The Harvard study didn&#8217;t just look those with a diagnosis but with COVID symptoms lasting four weeks or longer. But when applying similar criteria to the 23andMe data, our researchers also saw a one-and-a-half-fold increased risk of developing long COVID.
The Harvard study examined data from 54,000 individuals over a 19-month  period. About 3,200 of participants in the study contracted COVID. The 23andMe study included data from more than 100,000 individuals who reported contracting COVID-19. Of those, more than 26,000 reported that they had experienced long COVID. Over 7,000 of participants said they’d been diagnosed with it. Even after a year, more than 10 percent of those in 23andMe’s study  continued to have symptoms like brain fog, fatigue, and shortness of breath. It’s important to note that long COVID refers to individuals with symptoms that linger weeks, months, or longer after a COVID-19 infection.
<h2>23andMe Long COVID Findings</h2>
Data from 23andMe’s as-yet unpublished study<a href="https://blog.23andme.com/23andme-research/anxiety-depression-long-covid/"> first appeared on our blog. </a>It is part of<a href="https://blog.23andme.com/tag/covid-19/"> a series of studies</a> being conducted by 23andMe scientists since the beginning of the pandemic in 2020.
Among the areas of study is research on<a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/"> the role blood type plays</a> in severity and susceptibility to the virus. Our researchers have also drawn new insights into the genetics that influence<a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/"> different reactions</a> to COVID-19 vaccines. Earlier this year, 23andMe published a study in<a href="https://www.nature.com/articles/s41588-021-00986-w"> Nature Genetics</a> that identified genetic variants associated with the loss of smell or taste due to COVID-19. That paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.
The Harvard study and the preliminary 23andMe data offer more insight into the perplexing nature of long COVID. But the studies also offer another illustration of the broader health impacts of these kinds of psychological stressors.   
Find the full Harvard study<a href="https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2796097"> here</a>.

More on Psychological Distress and Risk for Long COVID

By Catherine Weldon and Stella Aslibekyan, Ph.D.* 
In what is among the largest studies of long COVID to date, researchers at 23andMe confirm that it disproportionately impacts women, and being diagnosed with depression or anxiety is associated with a more than a two-fold increase in risk for the condition. The study also found that about half of those with persistent symptoms are experiencing them for six months or longer.  
Even after a year, more than 10 percent of those who reported being diagnosed with long COVID continue to have symptoms like brain fog, fatigue, and shortness of breath. It’s important to note long COVID refers to individuals who have health effects that linger weeks, months, or longer after COVID-19 infection.
In regression analyses controlling for age, sex, and ethnicity, 23andMe researchers found that those who reported that they had depression or anxiety prior to COVID-19 infection had a two-fold increase in the risk of being diagnosed with long COVID, and having a cardiometabolic disease was associated with a 90 percent higher risk of being diagnosed.  Cardiometabolic diseases include conditions such as high blood pressure, coronary artery disease, type 2 diabetes, and high cholesterol.
23andMe data also indicate that more than half of the participants saw no difference after vaccination. Of those who did see a difference, approximately twice as many people reported improvement rather than worsening of some or all symptoms. 
<h6>Confirms Some Previous Findings</h6>
Preliminary data from the unpublished study indicates that women are at least twice as likely to be diagnosed with long COVID compared to men even when controlling for age, ethnicity, and related health conditions. This contrasts with the overall breakdown of those infected with COVID-19, where<a href="https://link.springer.com/article/10.1007/s42399-020-00341-w"> men are much more likely</a> to be infected than women. Men are slightly more likely to die from the virus as well, according to a<a href="https://www.sciencedirect.com/science/article/pii/S0277953622000193#!"> recent Harvard study</a>.
The 23andMe study data is also consistent with<a href="https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00629-7/fulltext"> other studies</a> that have found women are much more likely to develop long COVID. More than 78 percent of those diagnosed with long COVID in the study were females, compared to about 62 percent among those who reported not having experienced long COVID. The findings in our study are aligned with other studies, including a <a href="https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00629-7/fulltext">study</a> led by researchers at the University of Milan that found that women were more than three times as likely to develop long COVID than men.
23andMe’s data also indicated that when compared with men, a larger percentage of women with long COVID appear to have symptoms that persist a bit longer, which is also consistent with<a href="https://www.liebertpub.com/doi/10.1089/jwh.2021.0411"> other smaller studies</a>. In addition, long COVID disturbs menstrual cycles; according to 23andMe’s data, about a quarter are reporting that they are still dealing with disruptions after a year. 
Beyond the disproportionate impact on women, those who have had the most severe cases of COVID are also at a much higher risk of developing long COVID. In the 23andMe study, researchers found that individuals with COVID who required hospitalization had a more than ten-fold risk of being diagnosed with long COVID compared to those who were not hospitalized when controlling for age, sex, and ethnicity. 
<h6>Very Large Study Cohort</h6>
Scientists still don’t understand what causes long COVID, nor how to best treat it. An effort to recruit patients to study the condition by the National Institutes of Health got off to a slow start, with the agency only recruiting about 1,300 people by late March, far short of their 40,000-patient goal.
The 23andMe study included data from more than 100,000 individuals who reported contracting COVID-19. Of those included in this study, more than 26,000 reported that they had experienced long COVID, and over 7,000 said they’d been diagnosed with it. This unpublished study is part of <a href="https://blog.23andme.com/tag/covid-19/">a series of studies</a> being conducted by 23andMe scientists since the beginning of the pandemic in 2020.
Among the areas of study is research on <a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/">the role blood type plays</a> in severity and susceptibility to the virus, and insights into the genetics that influence <a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/">different reactions</a> to COVID-19 vaccines. Earlier this year, 23andMe published a study in the journal<a href="https://www.nature.com/articles/s41588-021-00986-w"> Nature Genetics</a> that identified genetic variants associated with the loss of smell or taste due to COVID-19. That paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.

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Long-Haulers and Sex Differences
This latest study is part of an effort to better understand the so-called<a href="https://www.nature.com/articles/s41592-021-01145-z"> long haulers</a>: individuals with health effects that linger weeks, months, or longer after COVID-19 infection.
Why do some individuals continue to have symptoms long after the initial infection? Why are women more likely to develop long COVID than men, and what is the role of genetics in this?
While the 23andMe researchers found no genetic variants associated with developing long COVID, the higher rate of cases in women may be indicative of differences in hormonal levels, which are substantially rooted in genetics.
The sex differences do suggest biological underpinnings and can help elucidate them.  
Scientists know there are similar differences for other kinds of conditions. For example, women are much more likely than men to develop autoimmune conditions such as lupus or multiple sclerosis. Autoimmune conditions occur when the body’s immune system misfires and attacks healthy cells in the body. Females typically have two copies of the X chromosome, which has the largest number of immune-related genes. That in turn means that different immune responses are more pronounced in women.
Whether this explains the much higher incidence of long COVID in women has yet to be determined. But 23andMe researchers did find that about a third, or 32 percent, of those diagnosed with long COVID had some sort of autoimmune disease, compared to only about 20 percent among those who reported not having experienced long COVID. 
<h6>Serious Symptoms</h6>
<div style="float: right; text-align: justified; width: 315px; background-color: #eee; padding: 15px; margin-left: 10px;">
<ul>
<li style="font-weight: 400;" aria-level="1">Among the largest long COVID studies to date using self-reported data from more than 100,000 individuals consented to participate in research.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">Females are more than twice as likely to be diagnosed with long COVID compared to males when controlling for age, race/ethnicity, and related health conditions.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">Long COVID Symptoms linger past 12 months among at least 10 percent of those with long COVID.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">More than half of those with Long COVID had a history of depression, anxiety, or cardiometabolic disease prior to COVID-19 infection.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">Having a history of depression or anxiety was associated with more than a two-fold increase in the risk of being diagnosed with Long COVID.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">Having a cardiometabolic disease is associated with an approximately 90% higher risk of being diagnosed with long COVID.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">About a third of those who develop Long COVID have an autoimmune disease.</li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">More than half of the participants saw no difference in symptoms after vaccination. Of those who did, almost twice as many reported improvement in symptoms compared to those who reported worsening symptoms. </li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">Hospitalization for COVID led to a ten-fold increase in the risk of being diagnosed with long COVID. </li>
</ul>
<ul>
<li style="font-weight: 400;" aria-level="1">This unpublished study is part of <a href="https://blog.23andme.com/tag/covid-19/">a series of studies</a> being conducted by 23andMe scientists since the beginning of the pandemic in 2020.</li>
</ul>
</div>
Although trend lines are pointing downward for infections, hospitalizations, and deaths due to COVID-19, the impact of long COVID remains unknown. The condition is thought to affect as many as <a href="https://www.bmj.com/content/373/bmj.n1626">30 percent</a> of those who are infected with the virus.
23andMe’s study found that symptoms lasted from three months to more than a year, with some individuals continuing to suffer. The top symptoms– which the participants reported arose only after the COVID-19 infection– were brain fog, fatigue, and shortness of breath.
Among those diagnosed with COVID-19, even at six months about 34 percent of those diagnosed with the condition reported an inability to focus or concentrate associated with what’s termed “brain fog.” After a year, about 19 percent still had brain fog. After 12 months, about 14 percent reported having shortness of breath, and about 7 percent said they had heart palpitations.
<h6>What’s Next</h6>
There are a few limitations to our study that we should note. For one, this study relies on self-reported data from 23andMe consented research participants. As with other studies on long COVID, the diagnosis is still nebulous and highly variable, and the reports can be subjective. We include both information from those participants who reported that they were diagnosed with long COVID or simply reported that they had long COVID. 
Another important consideration is that 23andMe’s data is not representative of the U.S. population as a whole. That said, the prevalence of various symptoms is similar to that in the published literature. 
Future studies are warranted to continue documenting the natural history of long COVID over longer time periods. In addition to corroborating our findings, it is possible that future studies of even larger populations will find some genetic underpinnings of the reported symptoms, although the individual effect of each genetic factor is likely to be small. 
As people continue to deal with symptoms of long COVID, using studies like ours to better understand the illness will be increasingly important. Projecting over the millions of individuals worldwide who’ve been infected or are yet to be infected, the public health impact of long COVID is likely to linger for years to come. Understanding the underlying biology and associations may help as scientists wrestle with the best way to treat the condition.
<hr />
*Catherine is an associate scientist at 23andMe and Stella is a genetic epidemiologist at 23andMe.
<hr />
Editor&#8217;s note: Throughout this post we use the word women for simplicity, but the study was actually based on anyone with XX chromosomes. So &#8220;women&#8221; in our study may include people whose gender identity is different than the sex they were assigned at birth.

Anxiety and Depression Raise the Risk for Long COVID

23andMe’s research that has identified genetic variants associated with the loss of smell or taste due to COVID-19 was published today in the journal <a href="https://www.nature.com/articles/s41588-021-00986-w">Nature Genetics</a>. 
As part of 23andMe’s ongoing research on COVID-19, the findings were<a href="https://blog.23andme.com/23andme-research/scientists-find-genetic-link-to-loss-of-smell-among-covid-19-patients/"> first reported</a> in June of last year. The paper offers more detail on the study, which identified variants near two olfactory genes — UGT2A1 and UGT2A2.
&#8220;We&#8217;re delighted to see this manuscript published,” said Adam Auton, 23andMe’s Vice President for Human Genetics. “It is another example of how data contributed by 23andMe customers can provide unique insights into COVID-19. It really wouldn&#8217;t be possible without our customers, and we&#8217;re extremely grateful to everyone that participated in this research.&#8221;
<h2>Common Symptoms</h2>
Loss of smell and or taste, also called anosmia, is a hallmark symptom of COVID-19. It is often the earliest indication of infection, and in some cases, the only symptom. An individual with one copy of the variant is about 11.5 percent more likely to lose their sense of smell or taste if infected compared to someone with zero copies.
For this work researchers* conducted a genome-wide association study (GWAS) using data from more than 69,000 23andMe customers who consented to participate in research.  Along with identifying variants implicating the two olfactory genes, the study also noted that loss of taste and smell after COVID-19 was most common among women and younger research participants. It was less common among research participants of East Asian or African American ancestry.
<h2>Long Haulers</h2>
The research is part of ongoing work by 23andMe since the beginning of the pandemic in 2020. Among the areas of study is research on<a href="https://blog.23andme.com/23andme-research/23andme-covid-study-published/"> the role blood type plays</a> in severity and susceptibility to the virus, and insights into the genetics that influence<a href="https://blog.23andme.com/23andme-research/reaction-to-covid-vaccine/"> different reactions</a> to COVID-19 vaccines. In addition, researchers are currently studying so-called long haulers, individuals with continued health effects weeks, months or longer after infection, to determine whether genetics plays a role.
For the loss of taste and smell study, the researchers found that about two-thirds of participants who tested positive for the virus reported loss of smell or taste. In addition, the researchers working on this study also ran separate GWAS for individuals of European, Latino, African American, East Asian, and South Asian ancestries, and then combined the data via a meta-analysis. The researchers found the risk variants for loss of taste or smell most common among people of European ancestry, and least common among those of East Asian ancestry.
Because the novel coronavirus SARS-CoV-2 first enters the body and accumulates in olfactory support cells, the findings may offer researchers important insights into the biological pathway for infection. 
To read the full paper go to <a href="https://www.nature.com/articles/s41588-021-00986-w">Nature Genetics</a>.  You can learn more about 23andMe&#8217;s COVID-19 study <a href="https://you.23andme.com/covid19-study/">here</a>.
Many thanks to the over 1 million research participants who answered our questionnaire and made this research possible. 
<hr />
*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, Daniella Coker, Janie Shelton, 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.

23andMe Study on Loss of Smell and Taste Due to COVID-19 Published

What stories and breakthroughs shaped the year in science and genetics? 
That was the question we asked a group of 23andMe leaders who are experts in everything from human genetics to product science to diversity, equity, and inclusion.
Their wide-ranging responses span disciplines. You’ll find biology breakthroughs, public health declarations, illuminating visualizations, AI technologies, and rigorous scientific debates. 
COVID-19 is well represented in their answers, too, including new gains in scientific literacy as we continue to add terms like “spike protein” and “T cells” to the lexicon. 
The result is a list that collectively embodies our <a href="https://www.23andme.com/about?bst=pff">core value</a> of scientific discovery and captures a year of progress. 
<h2>Virology, Variants, Vaccines: A New Era of Scientific Literacy </h2>
<a href="https://mediacenter.23andme.com/press-release/23andme-announces-the-appointment-of-joseph-r-arron-m-d-ph-d-as-chief-scientific-officer">Joe Arron</a>, Chief Scientific Officer

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“Any way you slice it, the biggest story of the year — genetic or otherwise — is the coronavirus pandemic. The global scale of COVID-19’s effects on health, politics, economics, and culture is staggering, but observing biology plays out in real-time has been equally staggering. 
I have been struck by the dramatic rise in scientific literacy across our society. This is partly because scientists, journalists, and politicians have worked to understand and explain rapidly changing developments in viral variants, vaccines, antiviral therapies, epidemiology, and public health guidelines. These explanations often use technical molecular terms that have become part of our everyday language. 
For example, soon after the Omicron variant of SARS-CoV2 was discovered and sequenced, you could find visualizations of a <a href="https://www.nytimes.com/interactive/2021/12/14/science/omicron-variant-science.html">molecular model of the spike protein</a> mutations in the media. As an immunologist, it’s gratifying to see both the public’s interest in such things as antibodies, T cells, and viruses, as well as the patience and enthusiasm with which my colleagues endeavor to explain these complex processes in accessible language. 
While we all hope that this pandemic will soon recede into memory, I also hope that our society will remain engaged in seeking a deeper understanding of science, medicine, and the power of genetic technology to benefit human health.” 

<h2>Racism is a Public Health Crisis for Black Americans</h2>
<a href="https://blog.23andme.com/articles/melinda-king/">Melinda King</a>, Director of Diversity, Equity, and Inclusion and People Business Partner

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“I read an article from 60 Minutes on CBS News recently that shared what most healthcare professionals already know: there is a healthcare disparity gap for minorities compared to their white peers. There are many reasons for this gap, many of which are rooted in the by-products of systemic racism. However, Dr. David Williams, a professor and chair at Harvard’s T.H. Chan School of Public Health, has spent his career researching and sharing information on what the CDC now recognizes: racism itself can be a killer.
Dr. Williams classifies the various levels of mistreatment using an <a href="https://scholar.harvard.edu/davidrwilliams/node/32397">Everyday Discrimination Scale</a>, which includes nine elements designed to assess an individual’s daily experience of discrimination. The scale tries to gauge well-being by asking questions like: 
<ul>
<li style="font-weight: 400;" aria-level="1">How often are individuals treated with less courtesy than others? </li>
<li style="font-weight: 400;" aria-level="1">How often are individuals treated with less respect than others? </li>
<li style="font-weight: 400;" aria-level="1">How often do they receive worse service in restaurants or stores? </li>
<li style="font-weight: 400;" aria-level="1">And how often do people act as if they’re afraid of them?</li>
</ul>
Individuals with a high score tend to also have adverse health outcomes. A high score is associated with high blood pressure, diabetes, cardiovascular disease, and poor mental health.
Dr. Williams’s research also demonstrates that the health of Black Americans suffers whether they are rich or poor, well-educated or not. For example, Black women with college degrees are more likely to see their babies die as infants than white women who didn&#8217;t finish high school. Even when they are treated in the same healthcare settings, Black Americans receive worse care. 
While there is nothing new for me from this article, this has been my ancestors&#8217; journey. And I appreciate the research that supports what we know — racism is a killer. To improve the health and well-being of minorities, we have to spend an equal amount of energy on eliminating racism. 
As a company that leads with science and is focused on improving the health outcomes for everyone, this provides us with another angle to help close the healthcare gap. As we work to conduct research and develop therapeutic solutions, we should also focus equal time and resources to eradicating racism.” 

<h2>Predicting Protein Structures with Atomic Accuracy</h2>
<a href="https://investors.23andme.com/corporate-governance/leadership">Adam Auton</a>, Vice President, Human Genetics

	<figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="400" height="266" src="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2009/10/dnaoragami.jpg" alt="" class="wp-image-5013" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2009/10/dnaoragami.jpg 400w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2009/10/dnaoragami-300x200.jpg 300w" sizes="auto, (max-width: 400px) 100vw, 400px" /></figure>
	
“The<a href="https://deepmind.com/blog/article/alphafold-a-solution-to-a-50-year-old-grand-challenge-in-biology"> AlphaFold publication</a> is likely the most impactful research of the year regarding our ability to accurately predict protein structure. 
Understanding protein structure is critical for understanding biological function; knowing how a protein folds allows us to understand its shape and the protein&#8217;s function following that shape. 
However, predicting protein structure from the DNA sequence has been challenging for decades. As a result, only a relatively small number of proteins have had their structures &#8220;solved&#8221; by experimental means. 
This year, the DeepMind team released their AlphaFold technology, which used Machine Learning techniques to make tremendous strides in improving protein structure predictions. This technology has now been used to make structure predictions for every protein in the human genome and really opens a door for understanding biology in a way that wasn&#8217;t possible before.

<h2>The Past – and Future – of mRNA</h2>
<a href="https://www.lemonaidhealth.com/meet-our-lemons">Paul Johnson</a>, CEO, Lemonaid, and Vice President, General Manager Consumer
“The Fast Company article, <a href="https://www.fastcompany.com/90664662/how-biontech-created-a-new-delta-focused-covid-vaccine-in-just-a-few-weeks">How BioNTech created a new delta-focused COVID vaccine in just a few weeks</a>, described how creating some vaccines has become almost as easy as updating software code using mRNA. That was unheard of until recently and is critical as we encounter future viral illnesses and variants. It also lets us re-imagine how we might retool existing vaccines.<img loading="lazy" decoding="async" class="alignright size-full wp-image-29419" src="https://blog-api.23andme.com/wp-content/uploads/2021/12/Vaccine.png" alt="" width="164" height="168" />
Much like software, it&#8217;s now possible for biology to be sequenced and programmed using a &#8220;platform technology&#8221; so that if you change a sequence of the code, it is stable enough that everything else remains the same.  What used to take years now takes weeks. Like many breakthroughs, this discovery of mRNA as a potential platform in care delivery was not an overnight success. It was a consequence of risk-taking, personal sacrifice, and resilience. 
This <a href="https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race/">background article</a> written before the approval of the mRNA vaccine is equally inspiring. It details the bold vision of Hungarian-born scientist Katalin Karikó, who spent the 1990s getting rejected for her grants for mRNA. 
In 1995, she was demoted when her bosses thought the pursuit of mRNA was a dead end. Yet, she persisted, and the foundational science behind her work is the pillar to our mRNA vaccines today.” 

<h2>Polygenic Scores Enter the Mainstream</h2>
<a href="https://blog.23andme.com/articles/be-fascinated-for-womens-history-month/">Shirley Wu</a>, Director, Product Science

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“While there have been many compelling genetics stories related to the COVID-19 pandemic, one theme in genetics that I’ve found very interesting this year was the conversation around polygenic scores. 
Polygenic scores are statistical models that combine the effects of potentially thousands or millions of genetic factors, sometimes alongside other factors, to predict the likelihood of a disease or trait in an individual. These started to become part of the academic sphere about five to eight years ago, but this year it became clear that they’ve entered the mainstream. 
Biotech and pharmaceutical companies are leveraging them to improve drug development, healthcare systems are beginning to apply polygenic scores to patient populations, and companies (including 23andMe) are offering them to consumers and healthcare providers. 
With that comes all the <a href="https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7" target="_blank" rel="noopener" data-saferedirecturl="https://www.google.com/url?q=https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7&amp;source=gmail&amp;ust=1641313460594000&amp;usg=AOvVaw09nnlrAHzEpbAqzEBbQVE3">challenges and debates</a> around ensuring validity, demonstrating utility, and ethical questions. Also, are models that predict traits like intelligence or neurodivergence <a href="https://www.newyorker.com/magazine/2021/09/13/can-progressives-be-convinced-that-genetics-matters" target="_blank" rel="noopener" data-saferedirecturl="https://www.google.com/url?q=https://www.newyorker.com/magazine/2021/09/13/can-progressives-be-convinced-that-genetics-matters&amp;source=gmail&amp;ust=1641313460594000&amp;usg=AOvVaw0TZiNtUsOxzKUYVlMWq8HN">appropriate</a>? And how do we address health disparities, given that most of the data underlying these models are from samples of European descent?
A common thread that ties this discussion to what we do at 23andMe is figuring out how to broaden access to the benefits of the genome in a responsible, science-driven way. I’ll follow closely where this conversation goes in the next year and beyond!”

The Genetics of Reactions to COVID-19 Vaccines

By Daniella Coker, MPH, and Janie Shelton, Ph.D.*
Several studies show the three COVID-19 vaccines being used in the United States — from Johnson &amp; Johnson (J&amp;J), Moderna, and Pfizer — are safe<a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html">1,</a>2 and effective2,<a href="https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/work.html">3</a>  and offer the best hope to beat the pandemic.2,4 And as so many of us have gotten vaccinated, it’s impossible not to notice that people react differently to the vaccines. Many people report having no reaction, while others feel sick enough to stay home in bed. 23andMe researchers wanted to know more about why. Is it due to the type of vaccine, our age, or something else?
To learn more about these differences we analyzed the data from more than 100,000 23andMe consented research participants and found that the second in the two-shot vaccine from Moderna produced the strongest reactions. We also learned that younger people and women tended to react more to the vaccine than others.
<h2>Get Vaccinated</h2>
But before going into what our researchers found, we should be clear: The side effects of vaccines are minimal, while the risks from the virus caused by COVID-19 are severe. This was further confirmed by new <a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e4.htm?s_cid=mm7032e4_w">data from the CDC</a>.  More than 35 million people in the United States have contracted the virus caused by COVID-19, and 614,000 of them have died. Even with the emerging Delta variant cases, the most significant risk is remaining unvaccinated. We encourage people to take the advice of healthcare professionals, the <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/advice">World Health Organization</a>, state and local public health officials, and the CDC and get vaccinated. 
23andMe’s researchers wanted to examine differences in how sick people felt after receiving the vaccines. Now that more than half the U.S. population has been fully vaccinated and about 60 percent have had at least one shot,<a href="https://covid.cdc.gov/covid-data-tracker/#vaccinations">5</a> our scientists wanted to explore how people react differently to different vaccines and what factors may influence those differences. This study does not look at adverse reactions but categorizes how people felt after they were vaccinated and compares the degree of “feeling sick” between three different vaccines.
For 23andMe’s study, consented research participants were asked three questions: (1) What was their most recent COVID-19 vaccination? (2) What symptoms, if any, did they experience? and (3) How sick did they feel afterward.
Most research participants reported that their most recent vaccination was their second dose of either the Pfizer (44%) or Moderna (38%) vaccine.

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Approximately half of respondents didn’t feel sick, 40% felt a little or somewhat ill, and 10% felt very or extremely sick. And to be clear, “feeling sick” as a reaction to the shot is not the same as being clinically sick from the virus and requiring hospitalization. 23andMe scientists sought to describe and characterize this wide range of reactions to the COVID-19 vaccines.
Here are some of the key findings:
<h2>The second Moderna shot seemed to produce the strongest reactions</h2>
Compared to the other vaccines, it was those people with a second dose Moderna vaccination who most often reported experiencing any symptoms (85%), and most often reported feeling either very or extremely sick (18%) after their vaccination. Again, these differences were not related to clinical outcomes. In other words, these are relatively modest reactions to the vaccines, but the vaccines still offered strong protection against the virus. In addition, these reactions were generally only for a couple of days after the vaccination. Whereas the severity of COVID-19 infections includes potential weeks or months of hospitalization or death. In addition, scientists still don’t fully know the timeline for so-called COVID-19 “longhaulers,” people dealing with lingering symptoms long after being infected.

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Fatigue, pain at the injection site, and muscle/body aches were the most commonly reported symptoms for all vaccine types. Yet, for every symptom (except nausea), a larger portion of Moderna’s second-dose recipients reported experiencing that symptom compared to recipients of other vaccines.

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And in logistic regression models controlling for key demographics (age, sex, BMI, ethnicity, education, and history of COVID-19 infection), having received a second Moderna shot was significantly associated with 3x odds of experiencing any symptom and nearly 1.5x odds of feeling very or extremely sick (as compared to J&amp;J).
So, you are not imagining things &#8212; if you got the Moderna 2nd dose and felt “under the weather”, you are not alone. A lot of people did (nearly 1 in 5), but for <a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/moderna-faqs.html#vaccine-safety-efficacy">94.1% effectiveness</a> against COVID-19, we are all applauding those of you who suffered through a few days of discomfort for your and the greater good.
<h2>A history of COVID-19 infection associated with feeling sicker </h2>
You may have heard the rumor that people who have had COVID-19 are more likely to feel sick after receiving a vaccine. According to 23andMe data, that seems to be true — a larger proportion of consented research participants previously infected with COVID-19 reported feeling sick for every degree of sickness (from “a little” to “extremely”) compared to those not previously infected with COVID-19. In fact, only a third of participants with a previous infection experienced no symptoms from their vaccine, compared to half of those without a COVID-19 history.

	<figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="285" src="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/How-Sick-do-you-feel.png" alt="" class="wp-image-29113" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/How-Sick-do-you-feel.png 512w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/How-Sick-do-you-feel-300x167.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
	
Even after controlling for the key demographic variables listed above, having a history of a COVID-19 infection increased your odds of experiencing any symptoms or feeling very/extremely sick after your vaccination, both by about 30%.
<h2>More and stronger reactions for women and younger individuals</h2>
Women were more likely to have any symptoms, have more whole body (systemic) symptoms, and generally feel sicker following their vaccination compared to men.  

	<figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="314" src="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccin-reaction-by-sex.png" alt="" class="wp-image-29114" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccin-reaction-by-sex.png 512w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccin-reaction-by-sex-300x184.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
	
In fact, after controlling for potential confounders, women were almost twice as likely as men to have felt very or extremely ill.
Similar trends were observed for younger individuals when compared to older folks. Those 40 years of age and younger experienced between 2 and 3 whole-body symptoms on average, and nearly a quarter felt very or extremely sick. By contrast, those at least 75 years old experienced between 0 and 1 whole-body symptoms on average, and only 4% felt very ill.

	<figure class="wp-block-image size-large is-style-default"><img loading="lazy" decoding="async" width="512" height="315" src="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccine-reaction-by-age.png" alt="" class="wp-image-29109" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccine-reaction-by-age.png 512w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2021/08/vaccine-reaction-by-age-300x185.png 300w" sizes="auto, (max-width: 512px) 100vw, 512px" /></figure>
	
These relationships between sex, age, and vaccine reaction held up, even after controlling for potential confounders.
<h2>How do the COVID-19 vaccines work?</h2>
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).<a href="https://www.healio.com/hematology-oncology/learn-immuno-oncology/the-immune-system/the-innate-vs-adaptive-immune-response">6</a>
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.
<h2>What does my vaccine reaction mean?</h2>
Trends identified in 23andMe data support what the vaccine clinical trials and other studies have observed — that certain groups of people are more likely to have felt sicker from their COVID-19 vaccination. These include:
<ul>
<li aria-level="1">Women<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7</a></li>
<li aria-level="1">Younger people<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7,</a> 8,9,<a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a></li>
<li aria-level="1">Recipients of a second dose vaccine (compared to their first dose)8,9,<a href="https://jamanetwork.com/journals/jama/fullarticle/2778441">11</a></li>
</ul>
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.<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438701/">12</a> Hormonal and genetic differences between the sexes may also play a role in how the immune systems of men and women respond differently to vaccinations. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438701/">12,</a><a href="https://www.sciencedirect.com/science/article/pii/S1028455920302175">13</a>
As we age, our immune systems tend to weaken.<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901832/">14</a> This 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.<a href="https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm">7,</a>8, 9, <a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a>
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. <a href="https://www.gavi.org/vaccineswork/why-vaccine-side-effects-might-be-more-common-people-whove-already-had-covid-19">15,</a><a href="https://www.nationalgeographic.com/science/article/why-vaccine-side-effects-really-happen-and-when-you-should-worry">16</a> This 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<a href="https://www.medrxiv.org/content/10.1101/2021.01.29.21250653v1">17,</a><a href="https://covid.joinzoe.com/post/vaccine-after-effects-more-common-in-those-who-already-had-covid">18 </a>and had higher levels of antibodies after a first dose,<a href="https://jamanetwork.com/journals/jama/fullarticle/2777171">19</a> compared 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.
<h2>The COVID-19 vaccines are still effective, regardless of your vaccine-related reaction</h2>
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&amp;J didn’t experience any systemic reactions.8,9,<a href="https://www.cdc.gov/vaccines/covid-19/info-by-product/janssen/reactogenicity.html">10</a> And 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 &#8211; and of the vaccines &#8211; takes place during the second, or adaptive phase of the immune response.”<a href="https://www.nationalgeographic.com/science/article/why-vaccine-side-effects-really-happen-and-when-you-should-worry">16</a>
<h2>What’s next?</h2>
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 the <a href="https://www.nature.com/articles/s41588-021-00854-7">susceptibility and severity of COVID-19</a> and looking at other aspects of the pandemic like its impact on <a href="https://blog.23andme.com/23andme-research/covid-impact-on-sleep/">sleep</a>, <a href="https://blog.23andme.com/23andme-research/stepping-back-up-amid-covid-19/">physical activity</a> and how it has <a href="https://blog.23andme.com/23andme-research/impact-disparities-of-covid-19/">hit some communities harder than others</a>. 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.
<hr />
*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.

COVID-19 Vaccine Reaction Data

Earlier this summer, a consortium that included more than 3,000 researchers and scientists from around the world jointly published a summary analysis on genetic clues linked to both the susceptibility to COVID-19 and to the most severe cases of people who contracted the virus.&nbsp;&nbsp;&nbsp;
Published in the journal Nature,<a href="https://www.nature.com/articles/s41586-021-03767-x"> the paper notes</a> 13 genetic associations found in genes or gene regions involved in such things as immune response, blood type, and lung disease.
The findings help shed light on the biological pathways in not just how people become sick with the virus but why some people become severely ill from it. The hope is that these <a href="https://www.23andme.com/dna-health-ancestry" target="_blank" rel="noopener">genetic insights</a> will help researchers hunting for therapeutics for treating the virus.
“The better we get at treating COVID-19, the better equipped the medical community could be to manage the disease,” said<a href="https://www.broadinstitute.org/node/7003"> Ben Neale</a>, co-director of the<a href="https://www.broadinstitute.org/node/8507"> Program in Medical and Population Genetics</a> at the Broad and co-senior author of the study. “If we had a mechanism of treating infection and getting someone out of the hospital, that would radically alter our public health response.”
But almost as striking as the genetic findings are the level of collaboration among scientists that formed into this loose consortium known as the<a href="https://www.covid19hg.org/"> COVID-19 Host Genetics Initiative</a>. The initiative began in March of 2020 by scientists at the<a href="https://www.fimm.fi/en/"> Institute for Molecular Medicine Finland, University of Helsinki</a>, and the Broad Institute of MIT and Harvard, and quickly grew from there.&nbsp;
Among the researchers are those from both the private and public sector, from academic institutions and public companies — including scientists from 23andMe — who joined forces to pool what they’ve learned.
“This has exceeded anything I’ve seen in my lifetime,” said Janie Shelton, a 23andMe senior scientist, and epidemiologist. “The rate we’ve been able to collaborate with international teams to uncover the genetic vulnerability to COVID-19 has been incredible.”
Over the last year, several participants in the initiative have already published their findings that ultimately became part of this broader paper. For instance, 23andMe published last June on our findings around genetic associations between the genes that <a href="https://blog.23andme.com/23andme-research/blood-type-and-covid-19/">influence blood type</a> and a person’s susceptibility to COVID-19 and the severity of their symptoms. This year, we published on genetic associations with COVID-19 and<a href="https://blog.23andme.com/23andme-research/scientists-find-genetic-link-to-loss-of-smell-among-covid-19-patients/"> loss of smell and taste</a>, as well as created a tool to help people better understand<a href="https://blog.23andme.com/health-traits/covid-19-severity-calculator/"> the non-genetic factors</a> that contribute to a higher risk for hospitalization due to the virus.
Since launching our<a href="https://you.23andme.com/covid19-study/"> COVID-19 Research Study</a> soon after the pandemic began, we have been sharing our findings with the broader scientific and medical community to help address this health crisis.
As Janie said in an interview earlier this year:
“It’s important for us to unveil our findings as publicly as possible.”
The researchers now plan to focus their attention on so-called “long-haulers,” people who have had the virus who continue to have symptoms for months.
You can read more about the paper<a href="https://www.nature.com/articles/s41586-021-03767-x"> here</a>.
&nbsp;

COVID-19