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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Oct 11 • 8 tweets • 3 min read • Read on X
Much-needed data on the genetics of #longCOVID in a new preprint by @23andMeResearch - GWAS of #LongCOVID identified 3 loci pointing to immune and thrombo-inflammatory mechanisms 🔥 @ninaadsc
1) HLA-DQA1–HLA-DQB
2) ABO
3) BPTF–KPAN2–C17orf58
(1/)
medrxiv.org/content/10.110…Image
Among research participants who reported acute SARS-CoV2 infection, 64,384 participants reported to have experienced Long COVID and 178,537 participants did not. Their analytical cohort consisted of 54,390 cases and 124,777 controls 👇🏼 (2/) Image
The top locus was in the HLA-DQA1–HLA-DQB intergenic region. Further analysis showed that HLA alleles HLA-DRB1*11:04, HLA-C*07:01, HLA-B*08:01, and HLA-DQA1*03:01 were significantly associated with #LongCOVID. In other words, crucial genes for T cell target detection! (3/)
Curious that the HLA-DQA2 gene identified to be expressed higher in those resistant to SARS-COV-2 sustained infection is also in the vicinity of that locus. (4/)

The second most significant GWAS link was found in the ABO gene. ABO blood group and has also been previously linked to COVID susceptibility and severity by others reviewed here. (5/) ncbi.nlm.nih.gov/pmc/articles/P…
The last locus identified contains at least 3 plausible causal genes; BPTF, KPAN2, and C17orf58. C17orf58 gene has been associated with posterior myocardial infarction; KPAN2 encodes importin α1 associated with viral suppression (6/)
biorxiv.org/content/10.110…
The authors then looked for genetic correlations with similar phenotypes and found the strongest correlations between #LongCOVID and chronic pain, chronic fatigue, fibromyalgia, and lupus. (7/) Image
These data provide a much-needed glimpse into the pathomechanism of #LongCOVID, pointing to biological differences in adaptive immunity, blood groups, and innate antiviral mechanisms. Thank you to all the authors for this important contribution 🙏🏼 (end)

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More from @VirusesImmunity

Prof. Akiko Iwasaki Profile picture
Oct 13
This time, we developed a nasal booster vaccine for influenza viruses. In this preprint, @MiyuMoriyama et al. show that nasal boosters with unadjuvanted hemagglutinin protein induce sterilizing immunity in mice against flu. (1/)
biorxiv.org/content/10.110…
This work builds on the Prime and Spike vaccine strategy by @tianyangmao @BenIsraelow et al. against COVID where mRNA vaccine followed by nasal booster with recombinant spike protein established local immunity, ⬇️ infection & transmission in rodents. (2/)
science.org/doi/10.1126/sc…
For Prime and HA against flu, @MiyuMoriyama tested several different mRNA IM prime and nasal HA booster doses, followed by a homologous influenza virus challenge. Like Prime and Spike, no adjuvant is needed for the nasal booster due to preexisting immunity from Prime. (3/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Oct 4
Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium Image
An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD Image
Where we need to go @MichaelPelusoMD Image
Read 4 tweets
Prof. Akiko Iwasaki Profile picture
Oct 2
Sharing this scoping review on "Post-Acute sequelae of COVID-19 in pediatric patients within the United States" by @ChrisMillerDO - an amazing @YalePediatrics infectious diseases fellow focused on research and treatment of #longcovidkids (1/)

sciencedirect.com/science/articl…
Key findings:
- Most pediatric LC patients were adolescents.
- ♀>♂️
- 80% of pediatric LC patients started with a mild initial infection.
- Asthma, atopy, allergic rhinitis (type 2 immune diseases), and obesity were frequently reported pre-existing conditions. (2/)
The most frequently reported symptoms in #longcovidkids are listed here (3/) Image
Read 4 tweets
Prof. Akiko Iwasaki Profile picture
Sep 27
An important study by F. Eun-Hyung Lee's team shows that long lived plasma cells (the source of long-term circulating antibodies) fail to establish after mRNA vaccination (even combined with SARS-CoV-2 infection). 🧵 (1/)
nature.com/articles/s4159…
The longevity of antibody-mediated protection against infectious diseases rely on whether or not the vaccines can establish long lived plasma cells (LLPC) in the bone marrow. They are the source of circulating antibodies for years to decades. (2/)
nature.com/articles/s4159…
Image
The study by Nguyen et al examined the long lived and short lived plasma cells in the bone marrow in people who received COVID mRNA vaccines, tetanus and flu vaccines at various time points . They found no LLPC (PopD) specific to COVID but found PopD against tetanus and flu. (3/) Image
Read 9 tweets
Prof. Akiko Iwasaki Profile picture
Jul 29
A new study led by @marioph13 in collaboration with the @WilenLab examines two bat coronaviruses that are the closest relatives of SARS-CoV-2 for their ability to infect, evade immunity and transmit between rodents. Some key takeaway points 🧵 (1/) nature.com/articles/s4156…
Here is a link to the accessible manuscript (2/)
rdcu.be/dPjsA
We used the highest biosafety level available at Yale (BSL3+) to conduct the study and we did not introduce gain-of-function mutations into the bat viruses. No serial passaging of the viruses were done - to avoid adaptation. Grateful to @YaleEHS for all the support. (3/)
Read 9 tweets
Prof. Akiko Iwasaki Profile picture
Jun 19
Sharing our new study by @keylas3, @SilvaJ_C, Rafael Bayarri Olmos et al (with T. Horvath & @PutrinoLab) showing that a passive transfer of IgG from patients with #longCOVID into mice recapitulates ⬆️ pain and other symptoms 🧵 (1/)

medrxiv.org/content/10.110…
Long COVID disease pathogenesis includes persistent SARS-CoV-2 virus, dysbiosis, herpesvirus reactivation, autoimmunity, and others. In this study, we focus on the role of autoantibodies. (2/) Image
Among the original Mount Sinai-Yale Long COVID study participants 👇🏼 (with @PutrinoLab), we focused on patients with high neurological symptom burden (n=55), and compared antibodies with convalescent controls (n=42) or uninfected controls (n=39). (3/)
nature.com/articles/s4158…
Read 20 tweets

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