#CDC has recently reported myocarditis & pericarditis cases following #mRNA #vaccination in adolescents & young adults in the US. Are these the first reported cases of cardiac involvement following mRNA vaccines? 1/
Fortunately, these incidents are extremely rare events. But, have the agencies overlooked earlier signals? Are these cases indeed related to mRNA vaccines? Are the vaccines responsible? If yes, what could be the probable mechanism? 2/
Few cases of post-vaccination myocarditis, heart failure & heart attacks have been reported in #Israel since December soon after the launch of #Pfizer mRNA vaccine. Health officials referred them as “A murky wave of heart attacks” 3/
There were few other media reports claiming a higher incidence of certain cardiac ailments following mass vaccination drive with #BNT162b2 vaccine in Israel 4/
Israel initially refuted any association to #Pfizer Covid vaccines. But now they said, “it had found the small number of heart inflammation cases observed mainly in young men who received Pfizer’s vaccine were likely linked to their vaccination”. 5/
In Israel, 275 cases of myocarditis were reported between December 2020 and May 2021 among more than 5 million vaccinated people 6/ Image
What could be the mechanism? Could it be due to #autoreactive antibodies responsible for #autoimmune myocarditis? Fortunately, majority of the cases are mild, self-limiting type. And above all, these events are extremely rare! 7/
A severe type might also be responsible for some of the post-mRNA vaccination sudden death reports which are being attributed to other adverse effects which are not directly related to #mRNA vaccine 8/
Several factors predispose the development of autoimmune myocarditis such as systemic/local primary autoimmunity, viral infection, HLA & gender bias, exposure of cryptic antigens, mimicry, & deficient thymic training/Treg induction pubmed.ncbi.nlm.nih.gov/28667560/ 9/
Once the anti-myocardium autoimmune process is triggered, several components of the immune response orchestrate a sustained attack toward myocardial tissues with particular timing and immunopathogenic features 10/
Covid19 itself can lead to fatal myocarditis. Proposed mechanisms include binding of Spike protein to ACE 2 which facilitates virus entry into the target cells, immune-related myocardial inflammation & direct injury caused by hypoxemia 11/ ebm.bmj.com/content/ebmed/…
There are some other possible mechanisms. It has been suggested that IL-6 plays an integral role in activation of helper T cells, which in turn release inflammatory cytokines ultimately resulting in myocardial inflammation and damage 12/
Another one...the SARS-CoV-2 spike protein disrupts the cooperative function of human cardiac pericytes - endothelial cells through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease 13/
Different mechanisms may lead to #myocarditis. What needs to be done? Since the nucleic acid-based vaccines are the new entrants, every possible safety signal must be promptly evaluated. Transparency in risk-communication is essential & it further enhances vaccine confidence 14/
The supraphysiological expression levels of spike proteins in some individuals who receive nucleic acid based vaccines might share in development of autoimmune reactions. There is a need to optimize the dose of the nucleic acid based vaccines to the lowest possible dose 15/
There is a need to develop potential tools to prevent such reactions. Fortunately, the risk is still miniscule considering the huge number of vaccines delivered so far. Still, the benefits far outweigh the risks. #Moderna has already started working on this aspect 16/
Additionally, the techniques used in development of all types of #SARSCoV2 vaccines, especially the newly emergency approved ones, should focus on innovative methods to decrease their potential #autoimmunity 17/ authorea.com/doi/pdf/10.225…

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More from @vipintukur

5 Jun
What does #HerdImmunity mean in context with #SARSCoV2?
We don’t need the entire population to be vaccinated or the vaccines to be 100% effective (they never are); we just need them to reduce infection rates enough to get us <1. That is herd immunity 1/

The issue is more complex. Despite achieving high seropositivity in certain regions, resurgences have occurred. And in certain regions/countries, the virus suddenly retracted even in the absence of a significant sero-positivity 2/
It is not a pure mathematics. There is an interplay of infection or vaccine-induced immunity & the evolution in the virus. The 'Ro' is not a fixed number--keep on changing with the virus transmissibility. With this changes the thresholds to achieve 3/
Read 6 tweets
4 Jun
How did #India fare? The graphic tells the whole story:
➡️Brutal onslaught by #B16172: having the highest transmissibility & most immune evader of all VOCs with higher virulence?
➡️No support from Vaccination (negligible coverage & high breakthrough, but reinfections rare) 1/
➡️ Social mitigation measures worked! Or the virus ran out of steam? Or still too early to conclude?
➡️ India struggled (significant mortality/health infrastructure collapsed) but survived!! 2/
New study on immune escape potential of #B16172 in comparison to #B1351 w/ #BNT162b2 vaccine: More immune evader than even B1351 VOC! Significant loss of antibody neutralisation vs live B16172 (-5.8x, akin to B.1.351) @TheLancet 3/
Read 6 tweets
29 May
We know that the two Ad-vector based vaccines, #AstraZeneca & #JNJ lead to clot-related complications like cerebral venous sinus thrombosis. We also know these events are referred to as ‘Vaccine induced Thrombotic Thrombocytopenia’ (VITT). But what lead to these complications? 1/
Now a new explanation for VITT seen with vector vaccines. “Vaccine-Induced #Covid19 Mimicry” Syndrome: Splice reactions within the #SARSCoV2 Spike ORF result in ‘Spike protein variants’ that may cause thromboembolic events in patients immunized with vector-based vaccines 2/
These soluble Spike #variants may initiate severe side effects when binding to #ACE2-expressing #endothelial cells in blood vessels 3/
Read 27 tweets
29 May
Now, it seems, we are close to solve this puzzle. A spurt of studies are favoring natural infection. In this new study from Lombardy, Italy, only 0.3% people got re-infected 1 Year after primary infection. Uninfected had 13-15 times higher infections 1/
Another study documenting at least 1 year protection following natural infection: medrxiv.org/content/10.110… 2/
Earlier we thought natural SARSCoV2 infection fails to produce long lasting plasma cells in the bone marrow. But now we have evidence 👇
Even mild #Covid infection induces a robust antigen-specific, long-lived plasma cells in 3/
Read 4 tweets
26 May
Shocking! Can’t the rich countries postpone vaccination of their less susceptible population & donate excess quota of vaccines to the underprivileged, LMICs of Africa?
Need such policies to spare more vaccine doses for the needy. We now have plenty of data on the futility of the 2nd vaccine dose to the pre-infected, seropositive individuals

This research has relevance to India also.
A single dose #ChAdOx1 nCoV-19 vaccine serves as an effective immune booster after priming with natural #SARSCoV2 infection up to at least 11 months post infection.

medrxiv.org/content/10.110… ImageImage
Read 5 tweets
21 May
Antibodies or the T-cells?

Which arm is crucial for viral clearance & protection against #SARSCoV2? 1/
Early on in the #pandemic questions arose regarding how #SARSCoV2 is cleared during acute/primary infection & what aspects of the #adaptive immune were necessary and sufficient for protection from repeat infection 2/
Using mouse models of SARSCoV2,@BenIsraelow Rt al demonstrate that both humoral and cellular adaptive immunity contributes to viral clearance in the setting of primary infection 3/
Read 9 tweets

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