1,168 karma · joined March 24, 2013
Dosing is done in Phase 1 trials, which also included antibody level testing. This has been already taken into account in the current trials.
> If millions of people take your early-release vaccine and it's ineffective
Phase 3 studies on Moderna, Pfizer, and AstraZeneca vaccines have shown that they are effective (and nowhere close to an "early release"). Statistics don't lie in that regard.
> This apparently is an issue with the Russian vaccine because of the way it's introduced to the immune system.
I'm not aware of any of such issues. Do you have a primary source I can look up?
Were it just me, I'd agree with you, however it is the data that we must look at:
https://science.sciencemag.org/content/early/2020/09/29/scie...
2 to 6 days incubation time is not "long".
> I am sympathetic to the idea but being overconfident
It's not being overconfident: it's what the currently available data says. The largest contact tracing study I am aware of, in India, reported that the largest cause of spread were superspreading events.
Long? The median is between 4 and 6 days. The 14 days often quoted is the 99th percentile. Can we stop perpetuating this myth?
> asymptomatic carriers makes for easy spread of the virus
Actually, most of the spread comes from superspreading events. Most people with the virus don't spread the virus at all, or spread it very little. True asymptomatic people are far less contagious than symptomatic people (up to 10 fold or so less). Severity of the symptoms is also associated with higher chance of spread.
> It will take something like 75% of the population to be immune (by vaccine or previous infection) to have effective herd immunity.
This is often calculated considering an equally susceptible population (which is not the case) with uniform mixing (same), so it's a very pessimistic estimate. The actual figure might be lower (though not as low as 20% as some "skeptics" say).
There are no long term studies. The reason vaccines take so much in "regular" circumstances are:
- Actually finding money to run the trials
- Run Phase 1, 2, 3 trials one after another
- (longest) Waiting for the events (infections) to accrue: if it's not in a pandemic, and with relatively low incidence, this takes years to happen
- Regulatory approval (if not in emergency, that's two years)
- Production scale-up (at least one year)
The fact that vaccines takes years to develop for safety is a myth. It is mostly a matter of time, and the fact that we were used to them taking years. Let's not forget smallpox and rabies vaccinations took far less to be invented, and people devising them didn't even know what viruses were. And also because most of the easy targets are now done. What's left are the harder ones (HIV). SARS-CoV-2 might have been hard, or one of the easy pickings. Luckily, it fell into the "easy" camp.
In this specific case, production was started during the trials, events, due to the fact that the virus is spreading like wildfire in the USA, took a matter of weeks to accrue (from 35 in October to 94 two weeks later, according to the Pfizer data), and the fact that an obscene amount of money was spent meant that most trials were started as soon as possible.
But, even looking at the protocols, you might notice that it ticks all the good boxes for proper clinical research.
And I ask because even the rarest documented effects occur within 3-4 months of administration, which is hardly long-term.
There may be a case for a specific Lyme disease vaccine, but thanks to the anti-vaxxers, the whole thing was withdrawn (against FDA recommendation) before the actual reason could be found.
mRNA vaccines had also (limited) human testing before these trials in the past years (mostly Phase 1).
https://www.fda.gov/media/144245/download
Writing a peer-reviewed paper two weeks after the data are out is hard, even more so when you have an emergency use authorization ongoing (which requires far more data).
First, this doesn't take into account the other tests developed around the world (China, CDC, Institut Pasteur).
> The described concentrations lead to increased nonspecific bindings and PCR product amplifications, making the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
In this "review" this hasn't been verified experimentally. The onus is on the ones doing the criticism. You still put excess primers in the reaction, because they don't need to be the limiting factor.
> 2. Six unspecified wobbly positions will introduce an enormous variability in the real world laboratory implementations of this test;
Has this been verified experimentally?
> 3. The test cannot discriminate between the whole virus and viral fragments. Therefore, the test cannot be used as a diagnostic for intact (infectious) viruses, making the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus and make inferences about the presence of an infection.
This is correct in absence of symptoms. But this test is meant as a diagnostic aid in presence of symptoms or any suspicion of SARS-CoV-2 infection. The fact that the governments don't use it like that does not invalidate the test per se.
> 4. A difference of 10° C with respect to the annealing temperature Tm for primer pair1 (RdRp_SARSr_F and RdRp_SARSr_R) also makes the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
This was tested in silico. There is no experimental evidence provided.
> 7. The PCR test contains neither a unique positive control to evaluate its specificity for SARS-CoV-2 nor a negative control to exclude the presence of other coronaviruses, making the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
Other tests used in the world, including the CDC, have those controls used for validation.
> 9. Most likely, the Corman-Drosten paper was not peer-reviewed making the test unsuitable as a specific diagnostic tool to identify the SARS-CoV-2 virus.
Ad hominem.
> In light of our re-examination of the test protocol to identify SARS-CoV-2 described in the Corman-Drosten paper we have identified concerning errors and inherent fallacies which render the SARS-CoV-2 PCR test useless.
What about the other tests elsewhere? Are they "flawed"?
The "authors" of this piece should have done like others did to uncover the poor specificity of early antibody testing: get some experimental samples, known positive and negative, and start doing experiments. Not writing a text with frankly dubious claims.
According to the data I've seen on kinetics (these vaccines have been in development since 20 years ago, so there's plenty of basic and animal test data) there's production of the antigen at the site of injection for approximately ten days. There's some systemic production in the liver for 2-4 days, but that's it.
The mRNA can last this long (normally, as you correctly say, it would get broken up in minutes) due to the lipid nanoparticles it is bound to, which are the "secret sauce" of this vaccine.
There are other tools out there for that kind of calculation, and to make sure it weren't an algorithm-specific problem they should also have used others.
Some:
- https://www.reddit.com/r/COVID19/comments/jo2muy/mink_and_co...
This is patently false, and the press have kept on saying it wrong to keep the terror giving them clicks. That mutation:
- Hasn't been observed in humans since Sep 5th;
- gives a slight advantage over escaping neutralizing antibodies (10%, not 100%)
- has no "fitness" at this point because there is no selective pressure for it
- has no effect on T cell based immunity
The Danish move was out of precaution, not because of the mutation, but because minks can become huge animal reservoirs of the virus due to the ease it spreads among them.
I'm surprised that the writer at the Financial (emphasis mine) Times did not know that.
The writer also does not seem to know about the recent immunity studies that show that it lasts for at least 8 months[1][2]. See also Derek Lowe's explanation on duration of immunity[3].
The press needs to do better!
[1] https://www.biorxiv.org/content/10.1101/2020.11.06.371617v1....
[2] https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1
[3] https://blogs.sciencemag.org/pipeline/archives/2020/11/18/va...
If we consider that recovered patients are immune between 6 and 8 months at least, that timeframe seems likely.
> What are the long term side effects?
I keep on asking myself. What vaccines do truly exhibit long term side effects? Narcolepsy with the 2009 swine flu vaccine or the Guillain-Barré syndrome for the 1976 flu vaccine do not fit the bill, because they actually showed up in the early months after administration (although some were found out later).
AFAICS, this is not BNT162b2, which is the one that we are talking about. There are 3 other candidates, one of them is the self-amplifying one.
No, in fact, mechanisms in cells are in places so that "heteroduplexes" (meaning one filament of RNA and one of DNA paired together) are quickly degraded.
Secondly, the RNA doesn't even need to get to the nucleus, where the DNA is. All it needs is to land in the cytoplasm, where it will get processed by the protein synthesis machinery (ribosomes in primis) to produce the antigen. RNA in the cell isn't that stable as well, so it will be ultimately get degraded.