This video shows that vaccines have helped some people with #longCOVID with their symptoms. While the numbers are still small in some groups, there are encouraging signs (also via @DanielGriffinMD).
I present my hypothesis on how vaccines might improve #LongCovid 🧵 (1/)
Back when I first learned about #longcovid in June 2020, I proposed 3 possible mechanisms.
1) Persisten viral reservoir
2) Viral fragments/remnants (RNA, protein) 'viral ghost’ driving inflammation
3) Autoimmune response induced by the infection (2/)

theatlantic.com/health/archive…
Since then, many studies have provided support for all of these. Viral reservoirs are found in tissues, viral RNA is found in non-respiratory tissues ⬆️ inflammation (@virusninja) 👇🏽, and diverse autoantibodies found in COVID patients (@Aaronmring). (3/)

cell.com/immunity/fullt…
These are not mutually exclusive mechanisms. If 1) is true, vaccine-induced T and Ab responses may be able to eliminate the reservoir. If 2) is true, vaccine-induced immunity may be able to eliminate the viral ghost if they are associated with the spike protein. (4/)
If 3) is true, still the vaccine might divert autoimmune cells (see below). I suspect that people with #LongCovid have varying degrees of 1), 2) and 3) taking place and are therefore should considered as heterogenous disease. Of course, other mechanisms can contribute. (5/)
Another possible way in which vaccines can help #longCOVID symptoms is through stimulation of innate immune responses (caused by vaccine-associated PAMPs). Transient inflammation might somehow divert the leukocytes causing #longCOVID (6/)

cell.com/cell/fulltext/…
If this is the case, the beneficial impact of vaccines will not be long lasting.
It is also possible that adaptive immune responses induced by vaccines divert the leukocytes causing #longCOVID - not clear for how long or how (7/)
To determine which mechanism(s) are responsible for vaccine-mediated improvement in #longCOVID, we can design a trial. Adding on @EricTopol;
A) mRNA SARS-CoV-2 Spike vaccine
B) mRNA irrelevant antigen vaccine (e.g. ZIKV)
C) mRNA not coding for protein
D) Placebo (saline)
(8/)
The outcome of the trial (summarized below) can tell us both what may be driving #longCOVID as well as possible therapy. Such a trial may be difficult for various reasons but is worth considering. Also, it would be great if there’s an animal model to try first. (9/)
If mRNA not coding protein improves #LongCovid even transiently, we can think of stimulating innate immune system using viral PAMPs or IFN-b periodically (kind of like MS therapy). Lastly, my hope is that the data from such trial may also inform treatment of #MECFS. (end)

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More from @VirusesImmunity

7 Feb
How well do various vaccines reduce severe COVID disease & death? Awesome @YaleMed students, @dariusdariusdar, @ChaneyKalinich, @Larson_HaleighT & Caroline Valdez put together summary tables from vaccine trials. Remarkable ability of vaccines to ⬇️ severe/lethal COVID! 🧵(1/n)
The phase 3 Pfizer BioNTech two-shot mRNA vaccine trial data. All the tables here and below indicate the # COVID-related death in the vaccinated as the right-most column (which is ZERO). (2/n)

nejm.org/doi/full/10.10…
The phase 3 Moderna two-shot mRNA vaccine COVE trial. (3/n)

nejm.org/doi/full/10.10…
Read 9 tweets
13 Jan
Top 10 most downloaded articles in 2020 includes our review in the @AnnualReviews Virology - “Seasonality of Respiratory Viral Infections” by @MiyuMoriyama et al! It’s free to download: arevie.ws/3aYt32Y

Here let’s highlight other relevant pieces on the same topic (1/n)
Just to recap, seasonal factors that drive respiratory tract viral infections are mainly these three;

1) ⬇️ Temperature
2) ⬇️ Humidity (esp. indoor)
3) ⬇️ Sunlight/Vitamin D

(2/n)
A twitter thread that demonstrates the importance of humidity on antiviral defense through mucociliary clearance measured by @Ericsongg. (3/n)

Read 11 tweets
10 Jan
What is the relevance of viral load in #COVID19 disease severity? A very talented @YaleMSTP student @SilvaJ_C found that saliva viral load to be a better predictor of disease than nasopharyngeal viral load. Here is a thread to explain the findings. (1/n)

medrxiv.org/content/10.110…
I preface by saying that numerous fantastic studies by many have demonstrated nasopharyngeal viral load to correlate with disease severity and mortality, while others do not find such correlation. Here are some of these studies. (2/n)
Being at @yale, the birthplace of #SalivaDirect and everything saliva bc of awesome colleagues like @awyllie13 @NathanGrubaugh @VogelsChantal et al, we had access to both saliva and nasopharyngeal (NP) samples from the same patients to do direct comparisons. (3/n)
Read 13 tweets
1 Jan
My first tweet of 2021 is going to be about 1 dose vs. 2 dose vaccine. I have tweeted in the past of the immunological advantages of a 2 dose vaccine. However, given the enhanced transmission variants on the rise, we need a modified strategy. (1/n)

theatlantic.com/science/archiv…
We typically give vaccines in more than one dose to increase 1) quantity, 2) quality, 3) longevity of antibody responses. This holds true for most vaccines including mRNA vaccines. Here is what I tweeted about this before. (2/n)

However, the 2 dose vaccine with limited number of vaccine means only half the people getting vaccinated at this time. If the virus is spreading slowly, we want to do the right thing and give the most vulnerable 2 doses and others to wait. (3/n)
Read 11 tweets
30 Dec 20
Inspired by this tweet by @TheMenacheryLab, I reached out to the wonderful colleagues at the @serimmune to see if the other mutations found in the B.1.1.7 variant would evade antibody responses generated by the wild type #SARSCOV2. (1/n)
According to this report, B.1.1.7 harbors non-synonymous mutations in the following viral genes, resulting in truncation, deletions and amino acid changes. Would these mutations result in evasion from antibodies generated by wild type virus? (2/n)

virological.org/t/preliminary-…
To probe this possibility, @serimmune used their technology platform based on bacterial display peptide libraries, next generation sequencing & machine learning to reveal antibody reactivity against WT and B.1.1.7 viral antigens. (3/n)

serimmune.com/technology.html
Read 11 tweets
26 Dec 20
What aspects of antibody responses determine the outcome of #COVID19? In this new preprint by @carolilucas @sneakyvirus1 et al., we found that the early timing of antibody response (before 14 days of symptom) in infected person is key to recovery. (1/n)

medrxiv.org/content/10.110…
As others have shown, we found that antibody levels from COVID patients correlated with disease severity.

journals.plos.org/plospathogens/…
wwwnc.cdc.gov/eid/article/26…

However, patients with lethal COVID did not have the highest level of anti-S or anti-RBD antibodies. What’s going on? (2/n)
To understand better the features of antibody responses in patients who died vs. survived, we compared their time course. We found a delay in antibody responses in lethal disease. We also noted patients with very high neutralizing Ab (HN) with very early antiviral Abs. (3/n)
Read 11 tweets

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