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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Sep 30, 2020 • 9 tweets • 7 min read • Read on X
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Are you confused about the role of type I interferons (IFN) in #SARS_CoV_2 infection?

Here is my speculation on what makes IFN-I helpful vs. harmful in #COVID19 patients - it comes down to timing and dose. A short thread.

All figures made by @BioRender & @annsea_park (1/n)
In the best case scenario, a rapid and robust induction of IFN-I should result in viral control and mild disease. This may happen in young people, or with low viral exposure settings. For a discussion we wrote, please read this.
(2/n)
cell.com/cell-host-micr…
In older adults or after high dose viral exposure, impaired IFN response early during infection results in enhanced viral replication, and prolonged levels of IFN-I and IFN-III responses that could result in pathological consequences and severe disease. (3/n)
Some papers supporting this scenario can be found here. (4/n)

immunology.sciencemag.org/content/5/49/e…

sciencedirect.com/science/articl…

rupress.org/jem/article/21…

nature.com/articles/s4158…

sciencedirect.com/science/articl…

science.sciencemag.org/content/369/65…

science.sciencemag.org/content/369/65…

stke.sciencemag.org/content/10/509…
Not all studies show this pattern. Here is a study that showed lower IFN-I levels in more severe COVID patients. It would be interesting to understand this difference. (5/n)

science.sciencemag.org/content/369/65…
In the setting of host genetic mutations in viral sensors, signaling molecules, adaptors, transcription factors; or in older people with neutralizing antibodies to IFN-I, little to no IFN-I is available. Uncontrolled virus replication can lead to very severe COVID-19. (6/n)
Papers supporting this scenario can be found here. (7/n)

science.sciencemag.org/content/early/…

science.sciencemag.org/content/early/…

jamanetwork.com/journals/jama/…
Finally, recombinant IFN therapy, especially given early during infection, can shut down viral replication and promote recovery. Further, prophylactic treatment with rIFN might be useful in high risk groups. (8/n)
A number of clinical trials are under way to test whether IFN therapy can help #COVID-19 patients recover quickly from infection and disease. Thank you for reading! (End)

clinicaltrials.gov/ct2/results?co…

sciencemag.org/news/2020/07/c…

covid19treatmentguidelines.nih.gov/immune-based-t…

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More from @VirusesImmunity

Prof. Akiko Iwasaki Profile picture
Feb 20
Our preprint on post-vaccination syndrome is out. We studied immune signatures and examined spike protein in the blood of people who have developed chronic illnesses after COVID-19 vaccination. (1/) medrxiv.org/content/10.110…
Vaccines have saved countless lives and inspired me to become an immunologist. While generally safe, some people experience adverse effects, including Post-Vaccination Syndrome (PVS). Studying PVS is crucial for improving patient care and enhancing vaccine safety & acceptance. (2/) pubmed.ncbi.nlm.nih.gov/37986769/
To explain the study and results, @MalloryLocklear wrote this excellent summary. (3/)
news.yale.edu/2025/02/19/imm…
Read 6 tweets
Prof. Akiko Iwasaki Profile picture
Nov 8, 2024
Happy to share our latest work by @YYexin et al. on antibody-mediated control of endogenous retroviruses in mice. In the process, we found “natural antibodies” with broad reactivity against enveloped viruses. Here is how “panviral” antibodies work 🧵(1/)

science.org/doi/10.1126/sc…
Endogenous retroviruses (ERV) are remnants of genetic invaders that have integrated into our ancestors' genomes over millions of years. ERVs occupy ~8% of the human genome and are under constant host immune surveillance. (2/)
nature.com/articles/nrg31…
nature.com/articles/nrmic…
This work started over 7 years ago when @YYexin and @rebecca_treger began to examine why ERVs reactivate in certain mouse strains. Through many genetic crosses, we figured out that secreted IgM recruits complement to suppress infectious ERV from emerging. (3/) Image
Read 16 tweets
Prof. Akiko Iwasaki Profile picture
Oct 13, 2024
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 11, 2024
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/)
Read 8 tweets
Prof. Akiko Iwasaki Profile picture
Oct 4, 2024
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, 2024
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

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