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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Jun 19 • 10 tweets • 4 min read • Read on X
What determines whether someone gets infected or not after exposure to SARS-CoV-2? A new study by Lindeboom et al examined this question with COVID-19 human challenge study. @BenIsraelow and I summarize their key findings in this News & Views 🧵 (1/)
nature.com/articles/d4158…
The study: 16 healthy young volunteers with no prior infection or vaccination were inoculated nasally with a low dose of pre-Alpha SARS-CoV-2 strain. Interestingly, only 6 had sustained infection, 3 had transient, and 7 had abortive infection at this dose. (2/) nature.com/articles/s4158…Image
The three infection outcomes allowed investigation of key features associated with susceptibility vs. resistance. Higher baseline expression of HLA-QA2 mRNA was associated with COVID resistance. Early nasal interferon I response was seen in those with transient infection. (3/) Image
In people who had sustained infection, local IFN I responses and cellular infiltrations were delayed (>5 days). Transiently infected people had rapid IFN-I and cellular recruitment into the nasopharynx (1 day). Adaptive immunity was induced only after sustained infection. (4/) Image
Curiously, in all exposed individuals regardless of infection outcomes, blood levels of activated monocytes declined while activated mucosal-associated invariant T (MAIT) cells were elevated ~3-10 days post-exposure. This feature may be useful as an early biomarker of viral exposure. (5/)Image
Of note, the HLA-DQA2 molecule may not operate conventionally as other MHC class II molecules. HLA-DQA2 is poorly polymorphic and highly conserved. It can pair with HLA-DQB2 to be expressed on Langerhans cells (antigen-presenting cells in the skin). (6/) doi.org/10.4049/jimmun…
Does HLA-DQA2 protein stimulate (unconventional?) T cells to provide COVID resistance? HLA-DQA2 mRNA might correlate with some other process that confers resistance. HLA-DQA2 alleles have been associated with diseases such as type 1 diabetes, rheumatoid arthritis, and Parkinson’s disease. (7/)
Fortunately, none of the challenged volunteers developed long COVID. This study provides key new insights into the immune signatures associated with sustained, transient, and abortive infection in human mucosa and blood. Congratulations to all the authors of this paper 👇🏼 (end) Image
I will post the article on SharedIt so you can read our News and Views, as soon as I receive the link from Nature.
Here is the SharedIt link to our piece


Thanks for reading!rdcu.be/dLjEt

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More from @VirusesImmunity

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
Prof. Akiko Iwasaki Profile picture
Apr 22
Preventing infection is the best way to avoid diseases like #PAIS. A new study from our team @tianyangmao, Jooyoung Kim, @marioph13 et al shows that a generic antibiotic neomycin acts on the host immune system in the👃🏽to trigger antiviral resistance. (1/)🧵
pnas.org/doi/10.1073/pn…
This work is inspired by @SmitaGopinath et al who showed that an antibiotic class called aminoglycosides has an unusual antiviral property. Aminoglycosides including neomycin trigger interferon-stimulated genes through a TLR3-dependent mechanism. (2/)
ncbi.nlm.nih.gov/pmc/articles/P…
In our current study, we showed that nasal application of neomycin in mice one day before infection reduces viral load and disease burden after the SARS-COV-2 challenge. @tianyangmao (3/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Mar 3
Delighted to share our latest work on #longCOVID - sex differences in symptoms and immune signatures. Led by @SilvaJ_C @taka_takehiro @wood_jamie_1 et al. with @LeyingGuan & @PutrinoLab. We find a striking inverse correlation btw testosterone levels and symptom burden👇🏼 (1/)

medrxiv.org/content/10.110…
This work leverages data from our recent Mount Sinai-Yale long COVID "MY-LC" study with the @PutrinoLab. This time, we asked the question, "Are there differences in symptoms and immune signatures of ♀️ vs. ♂️ with LC"? (2/)

nature.com/articles/s4158…
Image
While some symptoms were equally frequent in females and males, many were more frequent in females (e.g., swelling, headaches, muscle pain, cramps) than males. The top distinguishing symptoms of LC status by sex were hair loss in females and sexual dysfunction in males. (3/) Image
Read 16 tweets
Prof. Akiko Iwasaki Profile picture
Jan 13
In this prospective observational study, we examined changes in symptoms & immune phenotypes in vaccine-naïve people with #LongCovid after COVID-19 vaccination. Due to the timing of the initiation of this study, we were only able to recruit 16 people. However, the insights we gained are intriguing. Led by @connorbgrady, @bornali_27, @silva_JC, @hmkyale et al. (1/)
medrxiv.org/content/10.110…Image
This study was initiated in collaboration with @Survivor_Corps @dianaberrent based on their Facebook poll showing that 40% of respondents with self-reported Long COVID had mild to full symptom resolution after vaccination while 14% reported worsening of their symptoms. (2/)
doi.org/10.1101/2021.0…
In addition, evidence from other patient advocate groups, including @patientled and @longCovidSOS, and from @DanielGriffinMD, was emerging at the time on the impact of COVID vaccines in people with long COVID. (3/)
Read 19 tweets
Prof. Akiko Iwasaki Profile picture
Sep 25, 2023
So pleased to report that our Mount Sinai-Yale long COVID (MY-LC) paper with @putrinolab & others is now published!! Proud of the hard work of all who contributed. We found biological signatures that can distinguish people with vs. without #longCOVID (1/) nature.com/articles/s4158…
Question being asked: are there circulating cells & immune factors that are distinct in people with #longCOVID (LC) vs. those who recovered from COVID (convalescent control; CC) or those who never had COVID (healthy control; HC)? We studied 268 participants to address this. (2/) Image
Most participants were infected during the first wave in 2020, and studied on average about a year after the infection. Most were not hospitalized at acute phase and ~2/3 were female. We examined plasma factors, blood leukocytes & antibodies to SARS2, other viruses & self (3/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Aug 27, 2023
A short 🧵on a recent study by @MaggieLind2 with @MHitchingsEpi @datcummings Albert Ko et al. Data show that immunity induced by vaccines, prior infection or both (hybrid) protects against SARS-CoV-2 infection when viral exposure is low to moderate (1/)

nature.com/articles/s4146…
Question being asked: What is the risk of becoming *infected* with SARS-CoV-2 after developing immunity following a vaccine, prior infection, or both if exposure to the virus is very high, moderate, or low? They did not study the severity of symptoms. (2/)
How? The authors used the existing database of the Connecticut Department of Correction, where infection data based on high frequency of testing for SARS-CoV-2 on ~9300 residents across 13 facilities were available. (3/)
Read 9 tweets

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