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…
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/)
This lack of LLPC against the spike protein is also true for IgA-secreting plasma cells. IgA is an isotype of antibody that can be transported across the mucosal epithelial cells. Plasma cells secreting IgA may be present in the respiratory tract esp after infection (not tested here). (4/)
Can infection boost spike-specific LLPC in the bone marrow? The answer appears to be no. Vaccinated people who also had infection still made very little LLPC against spike. (5/)
In summary, this study shows that for some reason, vaccination against Spike with mRNA vaccine (even combined with infection) fails to establish long lived plasma cells that provide IgG against the virus long term. (6/)
Why is this? Is it the vaccine or antigen? We can test whether other vax platforms (subunit, viral vectored), routes (mucosal, epidermal) or adjuvants can overcome the limitations of establishing LLPC against spike. We may also need to modify the spike antigen to elicit LLPCs. (7/)
Note that current vaccines are still important, as they boost short-term antibody responses, restimulate memory cells, generate variant-matched immune responses...etc. But we can do better. (8/)
For example, nasal boosters given every few months may be able to maintain protective IgA in the nose and throat. Self-administration can make this easier. We need out of the box thinking to combat respiratory viruses like COVID and to prevent infection, transmission & #longCOVID (end)
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Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium
An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD
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/)
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/)
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/)
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/)
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/)
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…
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…
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/)
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/)