Are you going to take the COVID vaccine?

Originally Posted by nickolasanastasiou

I received the second dose on Wednesday. Tenderness at the site developed over ~6-8 hours and had vanished before 24 hours. At around 24 hours, I developed a temperature of 101.8F along with the slightest hint of aching muscles. I let that be for around 6 hours. Since I had to work that night, I took one 500mg tablet of acetaminophen that quickly brought my temperature to 98.8F and I have stayed around that since. Reactions will vary, but that was mine. All in all, no big deal relative to the benefit obtained.

You are probably following this much more closely than I am, but has there been any proven benefits of the vaccine yet? I know what they SAY it wil do, but I guess it's pretty hard to prove a negative. Since there are so many asymptomatic infections of COVID, how has the vaccine been "proven" to be effective?

Originally Posted by WebSlave

You are probably following this much more closely than I am, but has there been any proven benefits of the vaccine yet? I know what they SAY it wil do, but I guess it's pretty hard to prove a negative. Since there are so many asymptomatic infections of COVID, how has the vaccine been "proven" to be effective?

Yes. You can measure specific antibody avidity, which is how we tracked things when I worked in vaccine development. That, possibly used in combination with a volume quantification from serum samples, serves as a method for showing a competent immune response to a vaccine candidate. Further, one can, with enough sample size, compare the infection rate over a study's course of those enrolled who received a single dose to those who received two doses versus those who received placebo. Benefit is seen more directly in the rise of observable immunocompetence as well as somewhat indirectly via the reduction of detriment compared to those who did not receive the candidate. Some other companies have cancelled development of their vaccine candidates not because they did not work at all, but because they were not nearly as efficiacious as existing vaccines by Moderna and Pfizer. If the latter did not exist for comparison, and comparison is easy if the data are of quality and quantity, then cancelled candidates would have been progressed to the point of seeking approval (and probably receiving it) since expectations for vaccine efficacy have been traditionally far more conservative compared to the demonstrated results achieved via the big ones utilizing the current technology. It looks like we are doing a better job than we ever have before in several cases, but some betters are even better than other betters.

Thanks for such a comprehensive answer

My pleasure.

Originally Posted by nickolasanastasiou

Yes. You can measure specific antibody avidity, which is how we tracked things when I worked in vaccine development. That, possibly used in combination with a volume quantification from serum samples, serves as a method for showing a competent immune response to a vaccine candidate. Further, one can, with enough sample size, compare the infection rate over a study's course of those enrolled who received a single dose to those who received two doses versus those who received placebo. Benefit is seen more directly in the rise of observable immunocompetence as well as somewhat indirectly via the reduction of detriment compared to those who did not receive the candidate. Some other companies have cancelled development of their vaccine candidates not because they did not work at all, but because they were not nearly as efficiacious as existing vaccines by Moderna and Pfizer. If the latter did not exist for comparison, and comparison is easy if the data are of quality and quantity, then cancelled candidates would have been progressed to the point of seeking approval (and probably receiving it) since expectations for vaccine efficacy have been traditionally far more conservative compared to the demonstrated results achieved via the big ones utilizing the current technology. It looks like we are doing a better job than we ever have before in several cases, but some betters are even better than other betters.

So Nick, what is your take on the possibility or probability of potential long term detrimental effects from a vaccine of this type? Is Moderna using the same methodology as Pfizer? I thought I read somewhere that Moderna was developed in China, but not sure of the source of that information.

Yeah, I know you have had your shots, and I am presuming that you wouldn't have done that without feeling pretty good that you weren't dooming yourself to become a zombie in later years. But any reservations at all when you were waiting for the needle jabs?

Originally Posted by WebSlave

So Nick, what is your take on the possibility or probability of potential long term detrimental effects from a vaccine of this type? Is Moderna using the same methodology as Pfizer? I thought I read somewhere that Moderna was developed in China, but not sure of the source of that information.

Yeah, I know you have had your shots, and I am presuming that you wouldn't have done that without feeling pretty good that you weren't dooming yourself to become a zombie in later years. But any reservations at all when you were waiting for the needle jabs?

I am not concerned with that (long-term safety) being something of high probability or incidence. What lasts in the body is not the product, as the product is degraded very rapidly (mere hours; much faster than traditional vaccine components), but the immune memory (cellular) and the circulating antibodies. I think the only long-term question I have is the duration of protective benefit since we could not possibly have that data in hand yet. Will we need annual boosters? Every five years? I am curious about that part.

Similar mRNA technology for the two, although I think that they have somewhat differing drug product stability profiles for now (this is not relevant to safety, but can matter in terms of efficacy because the handling must be conducted within a storage and handling specification range in order to ensure that excessive degradation of the mRNA is not occurring prior to administration).

I have no worry about that, but for others due to specific data gaps. Young children. Pregnant women. I suspect that it will be expanded for children in time without it being a big deal, but we do not have data for it yet. I would not be comfortable giving this to pregnant women unless the risks of not getting it were somehow greater since I am deeply uncomfortable with things that put the unborn at risk. Some immunocompromised individuals plainly lack the machinery to do more than synthesize the protein that the mRNA codes for, so there would not be a direct benefit to them getting it if they cannot mount an immune response beyond the antigen/immunogen protein synthesis part of the process. There are probably some immunocompromised people who can gain partial benefit, but where that begins and ends will depend on various factors. Me not being as capable of getting infected now means my body is not likely to contribute to someone else becoming infected. That could be one of the people who cannot fight it off. Expand this to enough individuals and needless deaths start being prevented. Disease is indifferent, so whether it is a person I care about or someone I do not know, that I am doing something to reduce the risks to others in the process of protecting myself is a good thing. My vaccination improves the chances for my family and for strangers. In the sense of a butterfly effect, somebody somewhere that you do not know gets vaccinated who might have otherwise infected you or Connie and that can be the break in the chain that saves you or her. Likewise, if you feel up to it at some point, you can unknowingly break a chain for somebody you do not know. A pregnant lady. Someone frail. A kid. A regular and otherwise healthy adult that has crappy luck. Some other Rich's Connie. Some other Connie's Rich. There are good reasons to do it. Good enough reasons for me to choose to do it. I have taken care of quite a few Covid-19-positive patients, too, so my exposure risk is higher no matter what the PPE situation is (realistically speaking).

Variants Spreading in US Fan the Need to 'Crush' COVID-19 Quickly

Monday, 01 February 2021 12:44 PM

A COVID-19 mutation that likely confers partial resistance to the antibodies produced by vaccines is now in the U.S., spurring scientists to probe new ways to battle a disease that’s constantly changing and could remain active for years.

The South African variant has already spread quickly across the African continent and has been seen in at least 24 countries outside of Africa. It was reported in South Carolina on Jan. 28 and in Maryland two days later. If that looks like just a beachhead, note that a U.K. mutation first seen in Colorado on Dec. 29 has been detected in 29 U.S. states in less than a month. Both variants are considered more contagious than the original strain.

Late-stage trials released last week on vaccines developed by Johnson & Johnson and Novavax Inc. showed their shots to be generally potent against early forms of COVID-19. But results from studies done in South Africa told a less impressive tale. The J&J shot was found to be 72% effective in the U.S., but that fell to 57% in South Africa. Novavax’s shot, 89% effective in the U.K., was only 49% effective in South Africa.

The results are “sobering,” said Eric Topol, director of the Scripps Research Translational Institute in San Diego. “We see an unequivocal drop-off in efficacy.”

That means that vaccine makers must now divert attention to work on either booster shots or a new, adjusted vaccine that can work better against the South African mutation, known scientifically as B.1.351, even as the world is ramping up injections of the first shots put into use, he said.

“We are having enough of a struggle getting the first round of vaccines in,” Topol said.

Lab Tests

Before the J&J and Novavax results were made public, lab tests looking at the number of antibodies induced by vaccines from Pfizer Inc. and Moderna Inc. already in use suggest that while they may be less potent against the South African variant, they still had enough punch to hold it off.

But what that meant in terms of illness in the real world was unclear. The latest outcomes offer a more precise indication, said Anthony Fauci, the top U.S. infectious disease expert, on a conference call on Friday.

“It’s really a wake up call for us to be nimble, and to be able to adjust as this virus will continue for certain to evolve and to mutate,” he said. “Now we have the real-world clinical consequences, and we can see that we are going to be challenged.”

In statements at the New York Press Club on Friday, Fauci said it was “concerning that you need to stay ahead of these mutants, and essentially crush this outbreak so there’s no more replication. And when there’s no more replication, you’re not going to have any mutations.”

In laboratory results reported before the new Novavax and J&J trial data was in, scientists from the Aaron Diamond AIDS Research Center at Columbia University found that the Pfizer and Moderna vaccines were 6.5 to 8.6-fold less potent against the South African mutation.

100 Million Chances

“Looking at our results you cannot say this would doom the vaccine. That would be wrong,” said David Ho, who leads the lab. “But I think it is equally wrong to say everything is rosy.”

The world has “allowed the virus to infect 100 million people already,” he said. “So that is 100 million chances for mutation.”

The late-stage trials reported last week by J&J and Novavax could potentially pave the way for them to be authorized for use. J&J’s vaccine offers users a single shot regimen, as opposed to the two-dose versions authorized for Pfizer and Moderna. The drug giant plans to file this week with the U.S. Food and Drug Administration for an emergency-use authorization, company officials said. J&J’s top scientist said this month he expects clearance in March.

The Novavax shot, meanwhile, is likely to get its first approval in the U.K., and the company is discussing with U.S. regulators whether trial data from other countries could be part of the shot’s review, Chief Executive Officer Stan Erck said. Novavax is still recruiting patients for a trial in the U.S. and Mexico, Erck said in an interview on Bloomberg Television.

Still, Pfizer, Moderna, and J&J have all said they’re starting work on developing booster shots or other approaches to buttress their vaccines. It remains unclear how long the shots will immunize people against COVID-19, and new mutations may require changes in their makeup.

First Step

For the U.S., the first important step is to know when mutations are around. In another Friday briefing, Centers for Disease Control and Prevention Director Rochelle Walensky said the U.S. has now asked each state to send at least 750 samples a week to be sequenced to determine what variants may be here and how widely they may be spreading.

She warned that the existing U.S. system to detect different mutations is too slow for public health interventions to contain them.

“By the time someone has symptoms, gets a test, has a positive result, and we get the sequence, our opportunity for doing real case control and contact tracing is largely gone,” Walensky said. “We should be treating every case as if it’s a variant during this pandemic right now.”

While nations worldwide, including the U.S., are seeking to contain the spread of the variants with travel restrictions, history suggests that’s a near impossibility.

Industry Playbook

Meanwhile, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said the agency is seeking to finalize a playbook with the industry to address mutations.

If the agency feels the virus has drifted enough to require a different sequence, it will require small trials to make sure the vaccines produce an immune response, he said. The first few studies may have to go through an advisory committee, according to Marks, but the agency is looking to streamline the process as much as possible and may require less data over time.

“We would intend to be pretty nimble with this,” Marks said on an American Medical Association webinar, “so we get these variants covered as quickly as possible because it is clear they can spread pretty quickly.”

Long Fight

The bottom line from scientists: This is a fight that could go for a long time.

Vaccines that work well now may fade in the future unless strong booster shots are devised. And it could be that COVID-19 morphs into something akin to influenza, requiring periodic booster shots over the years to keep it at bay.

“The implications are really worrisome,” said Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College of Medicine, in an interview Thursday after the Novavax results were announced. “All the vaccine makers now have to make decisions” on how to proceed.

In the meantime, it’s now a race to vaccinate the U.S. and Europe before the South Africa variant becomes more common or, worse yet, new mutations develop that make the virus more resistant.

In his New York Press Club comments, Fauci was asked what keeps him up at night. His answer: “A mutant, where it really escapes everything.”

SOURCE: https://www.newsmax.com/newsfront/co...2/?oRef=vuukle