Covid-19 News

  • Pfizer and Biontech have not really explained how this new vaccine works. It sounds rather like the TB vaccine which peps up the immune system presumably readying it for attacks by other pathogens. Not much use, sorry to pour cold water over their rising share prices!:)

  • Spike mutation D614G alters SARS-CoV-2 fitness


    https://www.nature.com/articles/s41586-020-2895-3

    Abstract

    A spike protein mutation D614G became dominant in SARS-CoV-2 during the COVID-19 pandemic1,2. However, the impact on viral spread and vaccine efficacy remains to be defined. Here, we engineer the D614G mutation in the USA-WA1/2020 strain and characterize its effect. D614G enhances replication on human lung epithelial cells and primary human airway tissues through an improved infectivity of virions. Hamsters infected with the G614 variant produced higher infectious titers in the nasal washes and trachea, but not lungs, confirming clinical evidence that the D614G mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increases transmission. Sera from D614-infected hamsters exhibit modestly higher neutralization titers against G614 virus than against D614 virus, indicating that (i) the mutation may not reduce the ability of vaccines in clinical trials to protect against COVID-19 and (ii) therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this mutation in viral spread, vaccine efficacy, and antibody therapy.

  • Maybe it does, maybe it doesn't! Very elegant molecular biological research again showing how unlikely vaccines against the 700 known strains of COVID will ever be effective. And how many millions of shots of totally useless doses of vaccine has the UK government pre-ordered? Is this another exercise in lunacy like the rest of the way it has handled the pandemic so far?:)

  • Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells


    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915503/


    Endothelial dysfunction associated with vitamin D deficiency has been linked to many chronic vascular diseases. Vitamin D elicits its bioactive actions by binding to its receptor, vitamin D receptor (VDR), on target cells and organs. In the present study, we investigated the role of VDR in response to 1,25(OH)2D3 stimulation and oxidative stress challenge in endothelial cells. We found that 1,25(OH)2D3 not only induced a dose- and time-dependent increase in VDR expression, but also induced up-regulation of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR), as well as antioxidant CuZn-superoxide dismutase (CuZn-SOD) expression in endothelial cells. We demonstrated that inhibition of VDR by VDR siRNA blocked 1,25(OH)2D3 induced increased VEGF and KDR expression and prevented 1,25(OH)2D3 induced endothelial

  • Pfizer and Biontech have not really explained how this new vaccine works. It sounds rather like the TB vaccine which peps up the immune system presumably readying it for attacks by other pathogens. Not much use, sorry to pour cold water over their rising share prices!:)

    The Yahoo article says it uses the mRNA method, similar to Moderna's.


    "The Pfizer and BioNTech vaccine uses messenger RNA (mRNA) technology, which relies on synthetic genes that can be generated and manufactured in weeks, and produced at scale more rapidly than conventional vaccines.

    Moderna Inc, whose vaccine candidate employs similar technology, is expected to report results from its large-scale trial later this month.

    The mRNA technology is designed to trigger an immune response without using pathogens, such as actual virus particles."


    The better thing (to me) about this approach is that it doesn't use adjuvants (presumably).


    "The U.S. drugmaker said the interim analysis was conducted after 94 participants in the trial developed COVID-19, examining how many of them had received the vaccine versus a placebo.

    Pfizer did not break down exactly how many of those who fell ill received the vaccine. Still, over 90% effectiveness implies that no more than 8 of the 94 had been given the vaccine, which was administered in two shots about three weeks apart.

    The efficacy rate is well above the 50% effectiveness required by the U.S. Food and Drug Administration for a coronavirus vaccine."


    The problem is that the word "effective" is not defined, a tactic that is becoming more common in advertising.


    My guess is that "90 percent effective" means this: 90 percent of those getting the vaccine showed a reduction of certain symptom severity markers, compared to the average of those infected who didn't get the vaccine. If so, this would imply that not getting the vaccine was about 50 percent effective. ;)

  • The problem is that the word "effective" is not defined, a tactic that is becoming more common in advertising.


    My guess is that "90 percent effective" means this: 90 percent of those getting the vaccine showed a reduction of certain symptom severity markers, compared to the average of those infected who didn't get the vaccine.

    N.Y. Times:


    https://www.nytimes.com/2020/1…covid-vaccine-pfizer.html


    The company said that the analysis found that the vaccine was more than 90 percent effective in preventing the disease among trial volunteers who had no evidence of prior coronavirus infection. If the results hold up, that level of protection would put it on par with highly effective childhood vaccines for diseases such as measles. No serious safety concerns have been observed, the company said. . . .


    “This is really a spectacular number,” said Akiko Iwasaki, an immunologist at Yale University. “I wasn’t expecting it to be this high. I was preparing myself for something like 55 percent.” . . .


    Another interesting aspect of this report:



    . . . But Dr. Jansen sought to distance the company from Operation Warp Speed and presidential politics, noting that the company — unlike the other vaccine front-runners — did not take any federal money to help pay for research and development.


    “We were never part of the Warp Speed,” she said. “We have never taken any money from the U.S. government, or from anyone.” . . .

  • Maybe it does, maybe it doesn't! Very elegant molecular biological research again showing how unlikely vaccines against the 700 known strains of COVID will ever be effective.

    Vaccines usually target some strongly invariant rna sequences to bind with the virus. I think some subset of the spike protein should be used what also guarantees to block the lock!

    These vaccines are really are a next step in the fight against virus and its just a questions of costs whether a cocktail of rna antibodies is cheaper or a vaccine.

  • Just to be sure the article was not filling in the lines, I went to the source:


    https://www.pfizer.com/news/pr…vaccine-candidate-against


    • Vaccine candidate was found to be more than 90% effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis

    "Preventing Covid-19" would seem to mean : no symptoms, although they tested positive. That would be very good news.


    Pfizer was indeed part of Operation Warp Speed, in that they received an advanced guarantee that their vaccine would be purchased by the federal government. But ... unlike others they did not receive government funding for their R&D.

  • Quote

    A number of drugs that block il-6 are on the market to treat rheumatoid arthritis. They also can stop severe immune reactions in other situations, such as a cytokine release syndrome that can occur with some cancer treatments and with adult onset Still’s disease, a rare form of inflammatory arthritis. But, said Dr. John Stone, a professor of medicine at Harvard, “these are not infections.”


    HCQ is also used against arthritis, immunity modulation is actually its main usage today (malaria plasmodium has became immune to it). But from the same reason it will work mostly in early stage of disease, i.e. like prophylaxis drug. Once tissue capillaries get stuck with blood precipitate, then blood thinning agents aka warfarin/aspirin would work better. The modus operandi of these trombolytic drugs is sorta opposite to immunosuporessive drugs like HCQ, corticosteroids and IL-6 inhibitors: they make tissue more permeable for blood cells - not less.

  • "Preventing Covid-19" would seem to mean : no symptoms, although they tested positive. T

    It does not mean that. Preventing means preventing, not reducing the severity of the case. To be sure, there are many good therapeutics that reduce severity, even though the patient still gets sick. These are valuable. An influenza vaccine can reduce severity if you happen to get one of the strains not included in the four strains it is targeted for. However, "preventing" has a specific meaning. If they were to say "prevent" when they mean "reduce severity" they would get in huge trouble with Wall Street and possibly with the FDA.


    Preventing 90% of cases means that if enough people get the vaccine, the virus will go extinct in the human population, thanks to herd immunity. That will happen even if the effect of the vaccine wears off after a few years.

  • Quote

    The Yahoo article says it uses problematic, never approved yet mRNA method, similar to Moderna's:

    "The Pfizer and BioNTech vaccine uses messenger RNA (mRNA) technology, which relies on synthetic genes that can be generated and manufactured in weeks, and produced at scale more rapidly than conventional vaccines.

    Moderna Inc, whose vaccine candidate employs similar technology, is expected to report results from its large-scale trial later this month. The mRNA technology is designed to trigger an immune response without using pathogens, such as actual virus particles."

    An RNA vaccine consists of an mRNA strand that codes for a disease-specific antigen. Once the mRNA strand in the vaccine is inside the body’s cells, the cells use the genetic information to produce the antigen. This antigen is then displayed on the cell surface, where it is recognised by the immune system. Unlike a normal vaccine, RNA vaccines work by introducing an mRNA sequence (the molecule which tells cells what to build) which is coded for a disease specific antigen, once produced within human body, the antigen is recognised by the immune system, preparing it to fight the real thing.


    Normally the antigens are produced on let say yeast cells substrate, isolated, purified and transferred into human body, mRNA vaccine skips this step simply by making you the substrate for production of antigens. If you fear of GMO's from whatever reasons, then the mRNA vaccine is nothing for you: it will make you a GMO too... ;-)


    This method of vaccine application rises many questions for immunology: in many aspects it defies my understanding of how correct vaccine should behave.

  • From Ars Technica:

    mRNA vaccines have been a hot topic in research for several years, but so far, there are no licensed vaccines that use this method. This has given some experts pause about the ability to quickly scale up production. The vaccines also require extreme cold storage (-70 degrees Celsius in the case of BNT162b2), which adds to the daunting logistical challenges of vaccinating the worldwide population.

  • For example one can nowhere read, what so-called adjuvants are good for and why they're added to vaccines. My theory is, they usually come in form of precipitate, which mimic clusters of bacteria by binding antibodies on the surface of its particles, thus making them an easy target for T-lymphocytes, which are using to fight with infection.


    https://miro.medium.com/max/640/1*l6eSfhsGaIUwQWZd-HGJsw.gif


    Here it's apparent that lymphocyte navigates through gradient of antigen concentration, which bacteria leaves behind itself like hunting dog. When vaccine would remain widespread in low concentration across whole human body, then lymphatic cells would be produced, but they wouldn't know, where to go. Instead of particles of adjuvant they would attack the cells of human body, thus bringing some autoimmune disease.

  • Then there is another problem with mRNA vaccine concept. The immune system must somehow recognize, it got successful in fight with infection and to stop with random mutations of immune cells. I guess it recognizes it by gradual depletion of antibodies within organism during its successful fight with infection. Without it it will produce new and new types of immune cells increasingly susceptible to wider range of antigens, until it will start to generate immune cells which will become aggressive toward quite common proteins, like pollens, cat fur or myelin sheets of neurons. Autoimmune disease and allergy followed by chronic inflammation ensues again...


    In another words, prolonged exposition to antigens at low concentration also leads to sensitization and raise of allergy and autoimmune disease. The production of mRNA vaccine within human body therefore must stop soon - or it would lead into development of allergy and chronic inflammation - or even worse, into blastic crisis of lymphatic cells. The prolonged exposition to such vaccine thus may lead into even more violent cytokine storms, than without them!

  • Only 10 percent of the 94 confirmed cases were vaccinated. That would also be good news.


    10% of 94 cases is 9.4 person. This fractional number raises question by itself but Pfizer also says "Based on current projections we expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 202". How one can plan billion doses from 9.4 shots trial sample?

  • Zephir_AWT Yes. How does the immune system respond to human cells that are releasing some novel substances (coronavirus like antigens) long term? It might learn to ignore the antigen (unlikely) or it might start protesting against the type of human cells that are excreting the antigen (more likely), which may lead to an autoimmune problem. But I doubt the mRNA will be allowed to remain in the cell for long before it gets degraded.

  • Yea... Both Moderna, both Phizer are pretty secretive about how their vaccine actually works. For example Pfizer says, that vaccination consists of two shots, 21 days apart, and the 90%-plus effectiveness reading was measured seven days after the booster shot—or 28 days after the first shot. Moderna vaccine also consists of two shots...


    The antibody reserve introduced by shot must get depleted soon or later for to have vaccination working... My theory therefore is, the second shot actually disables the antibody production initiated by the first shot, thus prohibiting establishing of complications in form of allergy or autoimmune disease. But from existing information it seems both shots are essentially the same, they just differ by mRNA titre. They allegedly both contain lipid nanoparticle–encapsulated, nucleoside-modified messenger RNA (mRNA), that encodes the SARS-CoV-2 spike (S) glycoprotein stabilized in its prefusion conformation. Thus it may be also possible, that first mRNA from first shot gets depleted fast (which would give whole process at least some control) and second shot just replenished its load...


    I'd thus invite more information from both Moderna, both Pfizer regarding the explanation, how their vaccine is actually supposed to work, why two doses are needed instead of single one and all...

  • Only 10 percent of the 94 confirmed cases were vaccinated. That would also be good news.


    10% of 94 cases is 9.4 person. This fractional number raises question by itself but Pfizer also says "Based on current projections we expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 202". How one can plan billion doses from 9.4 shots trial sample?

    Probably it was 9 or 10 persons who were vaccinated that got Covid-19.

    According the the article they want to wait until the confirmed cases rise from 94 to 164:

    • Clinical trial to continue through to final analysis at 164 confirmed cases in order to collect further data and characterize the vaccine candidate’s performance against other study endpoints.

    At that point maybe 16 or so vaccinated people will have contracted Covid-19. Shouldn't take long given the numbers in the current wave.


    So far: safe and effective. Hope it stays that way!