Some interesting new molecular biology studies on SARS-CoV-2 that yield insight in the mechanisms of disease.

1/8 SARS-CoV-2 genes have functions in virus reproduction but also in:
- Undermining innate immunity by neutrophils
- Cell metabolism (glucose, hypoxia)
- Cell biology (mRNA splicing, transcription Protein polymerization, ER, Golgi)
nature.com/articles/s4158…
2/8

🇨🇳 Chinese paper suggest that >4💉would be detrimental. It is cheered by antivaxxers.

Good for in-depth look at paper.
💉A. Paper
💉B. Publicity
💉C. Data shown
💉D. Data not shown
💉E. Method used
💉F. Human data
💉G. Discussion.
💉H. Conclusion.
💉I. Notes.

1/16 💉A. Paper

🇨🇳 Chinese paper has provocative title:

"Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice"

Spoiler:
The title promises much more than the article does.

sciencedirect.com/science/articl…

2/16

Long COVID review.
>= 10% severe acute COVID19
>= 200 symptoms - multiple organ systems
>= 65 million individuals

After the acute disease by SARS-CoV-2, it is not over for a large subgroup.
nature.com/articles/s4157…

1/7 Systemic disease:
Impact on heart, lungs, immune system, pancreas, gastrointestinal tract, neurological system, kidneys, spleen & liver, blood vessels & reproductive organs.

Long covid morbidity goes beyond direct mortality
hartblik.weebly.com/diseaseoutnumb…
2/7

Paper investigates link between mRNA vaccination and myocarditis death. There were some worries about myocarditis in young men.

Evaluation of the evidence of 35 rare unexpected deaths after vaccination 🇩🇪.

1/6
link.springer.com/article/10.100… 35 unexpected deaths examined.

- 10 were under 40 years. None of these died due to mRNA vaccination (1 had AstraZeneca vaccine).

- The authors link 5 cases (46-75 years) likely/possibly to mRNA vaccination.

2/6

Nasal spray prevents 78% of SARS-2 infections.

Data sounds very interesting but some remarks.
- Young healthy participants ~ 34 (20s, 30s 40s)
- Many adverse events
- Juggling with numbers
- Many drop outs.
- Control data missing.
- Errors
1/9
medrxiv.org/content/10.110… Data errors (3x the same in paper!):
🧮135.544 = 27103 + 110441

It is not a major error but indicative for the data presentation.

2/9

Persistent infections in gastric and gallbladder tissue after SARS-CoV-2 infection.
- Detection of nucleoprotein (infection only - not in vaccine!)
- Up to 1 year (9-12 months) after infection.
- Especially with young people.
- Observed in 1/3 patients
link.springer.com/content/pdf/10…
1/3 SARS-2 viral persistence has been described before in the gut. ncbi.nlm.nih.gov/pmc/articles/P…
molecularcasestudies.cshlp.org/content/7/2/a0…
medrxiv.org/content/medrxi…

And found to be functionally important for the immune system 6 months after infection. 2/3
pubmed.ncbi.nlm.nih.gov/33461210/

💉Why are mRNA vaccines so effective?

After decades of trying to make mRNA stable enough to elicit immune responses they seem to outcompete all other vaccines:

💉>90% protection against severe disease compared to ~60% for other vaccine or previous infection

1/8 💉Even better protection from severe disease after boosting.

https://twitter.com/johnjljacobs/status/1606773862829625350

What is different about mRNA vaccines that makes them so effective.
A. Virology
B. Immunology

2/8

Time for a deep dive into SARS-CoV-2 immunology after vaccination and infection. I’ll try to explain it also for non immunologists.
New observation: Booster mRNA vaccines induce antibody switch to IgG4, what does this mean?
science.org/doi/epdf/10.11…
pubmed.ncbi.nlm.nih.gov/36548397/
1/ It is known that immune responses could either protect against disease or exacerbate disease.
Early non-neutralizing, afucosylated IgG1 antibody responses are associated with COVID-19 severity.
pubmed.ncbi.nlm.nih.gov/35040666/
pubmed.ncbi.nlm.nih.gov/36385627/
2/

Covid reinfection has higher higher ratio (HR) of death (2.17) hospitalization (3.32) and sequelae #longcovid incl. pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders.
1/
nature.com/articles/s4159… Hazard ratio in the left column. Note all are above he dotted line at 1 (same risk as 1. infection).
2/

Study showing intracellular LINE-1 reverse transcriptase in a liver cell line is able to perform RT activity on mRNA of Spike protein and allow DNA integration.
It is quoted as evidence that vaccination #Pfizer is dangerous, but
mdpi.com/1467-3045/44/3…
1/4 1. The human liver cell line is a cancer cell line that could only survive in petri dish, not in a human.
2. LINE-1 can indeed perform RTase activity for mRNA but would not discriminate between virus and vaccine.
Involved in multiple human diseases. pubmed.ncbi.nlm.nih.gov/9621510/
2/4

Remarkable paper.
Not peer reviewed but highly opiniated.
Ignoring completely the risk of a SARS-2 infection and not citing all the papers that give contra evidence.
Hard to call this science anymore.

https://twitter.com/Medscape/status/1498674429194387468

Heart-disease risk soars after COVID — even with a mild case. nature.com/articles/d4158…
Long-COVID symptoms less likely in vaccinated people, Israeli data say.
nature.com/articles/d4158…

🇺🇦🇷🇺
My first thought was that #Ukraine would not stand a chance against #Russia in the lowlands, but #Putin dismantled the Russian army from information, GPS, gas and food.
The invading army is unprepared, similar to operation #Barbarossa.

https://twitter.com/nexta_tv/status/1498181493683802112

Lessons from other wars show that understanding how the army is welcomed, local information, supply chains of gas and food are crucial for the military success. In general these are hard to manage in the mountains, but there are already challenges in the lowlands.

Testen, vooral in de context van bron- en contact onderzoek #BCO is de standaard en efficiëntste manier virus epidemie bestrijding.

Vaccinatie gaat virus verspreiding niet voorkomen, en test, traceer en isoleer #TTI kan een lockdown voorkomen.
1/5
hartblik.weebly.com/TTI.html 🌧️Aantal #COVID19 besmettingen gaat in de herfst en winter toenemen.

💉Vaccinatie vermindert het aantal mensen dat ernstig ziek wordt met ~90%, maar als het aantal besmettingen 10x zo hoog wordt (2020 - 5%🇳🇱) dan liggen de ziekenhuizen overvol.
2/5
hartblik.weebly.com/vaccinatie.html

Interesting research and hypotheses on Adenovirus vector vaccines causing thrombosis. Might also be relevant for safety of Janssen J&J & Sputnik vaccine.
sciencemag.org/news/2021/04/h… Anti-Platelet Factor 4 (PF4) antibody seems not involved in #VITT - previously named #VIPIT.
Antibody-mediated vaccine-induced thrombotic thrombocytopenia.
assets.researchsquare.com/files/rs-40476…