I understand the normal research and development of a new treatment usually takes years of testing. Vaccines for Covid-19 have been developed. But, they are unavailable, allegedly, for 18 months of dosage testing. After a century of vaccine development, they should have a fair estimate of what the dosage will be. This is a "deadly pandemic" so I am suggesting that there are people who would be willing to take their chances with an early vaccine, rather than face a high mortality rate when they get the virus. For example, those over 65 with a history of multiple medical problems, and an estimated mortality rate of possibly or 30%, may gladly volunteer for the early vaccine (All wavers signed, of course). This is more urgent considering that our hospitals and ICU's, and ventilators are already at capacity, and may not be available when needed. (Evidenced from news report published recently) My knowledge of the vaccine industry leads me to believe that they could 'ramp up production' rapidly enough to protect the billion or so people who need it immediately.
JAMA: Gary J Ordog, MD:
March 19, 2020 COVID-19: Can We Expedite Treatment? Gary Ordog, MD, DABMT, DABEM | County of Los Angeles, Physician Specialist, Retired The authors discuss human rights pertaining to avoiding infection during the next 18 months. We are supposed to wait while a vaccine is tested for dosing schedule. "Flattening the curve" may only prolong the inevitable infection with the virus. What are our rights to preventative and curing treatments? The most vulnerable of our population currently appear to be older and medically compromised individuals. Also, the most severely ill will require ventilators, ICU beds and critical care staff, and all are currently utilized to capacity, resulting in an increasing number of newsworthy disasters already. I suggest that prophylaxis and treatment should be made available, as a medical right, in this time of impending catastrophe. Treatments that have not had time to advance to final approval may be beneficial for saving life or limb, with those patients on the exponential end of " the curve" probably glad to sign a 'waiver of liability.' As far as prophylaxis and treatment, I refer first to the vaccines that are being tested correctly and for dosage. With a century of vaccine research, I think they have a pretty good estimate of the required dose. Can we not ramp up production and start giving it to the most vulnerable, at least? Secondly, there are currently thousands of patients who have recovered from COVID-19, can these not be a source of gamma globulin for the more serious ill, at least? Stem cell lines are another possible therapy. Thirdly, there are various antiviral drugs which are safe and possibly effective but obviously have not had the time to be tested. For example, remdesivir appears to be effective against other Corona viruses, probably would have some effect against Covid-19. Could we not ramp up production of these agents and allow our vulnerable patients to have access to them, when otherwise it looks like high mortality and morbidity, with our only treatment available being "social distancing?" Thank you for allowing me to make these comments. GJO
Covid-19: Immediate Mass Vaccination Required to Restore World Economy.
Dear Dr Gary Joseph Ordog , things may not be so simple. Reports from Japan and China show that recovered COVID-19 patients may test positive again for the SARS-COV-2 virus:
https://www.forbes.com/sites/brucelee/2020/03/15/can-you-get-infected-by-coronavirus-twice-how-does-covid-19-immunity-work/#a0118f95c0f8
This means that quite a lot of people cannot be protected by vaccination, and they have to rely on their innate nonspecific immunity and good health in combat the SARS-COV-2 virus.
https://www.researchgate.net/post/As_a_result_of_widely_spreading_of_the_COVID-19_novel_virus_Id_like_to_share_this_poster_with_you_using_different_international_languages
Dr. Yu: Hopefully the cases you reference are somehow immune suppressed and not the "norm." If we can't mount an adequate immune response to this virus, then we are in worse trouble than I thought. But, this is an even greater reason to start immunizing with the best available vaccine immediately.
it must be tested because it may harm humans or have no effect.
This discussion as well as two others were combined and published as an article in JAMA. Thank you for your support.
June 16, 2020. As of this time, the temporary and temporal answer to this question is, so far, "no." No cure yet, but a lot of the research has been stymied by fraud with retractions, changing definitions on Death Certificates, a plethora of invalid studies with a lack of controls and blinding. We are left with vaccines, and those so far are somewhat questionable. The virus, like that of the common cold coronavirus, keeps mutating for one thing, the current vaccine candidates may cause an illness similar to the disease they are trying to cure. Herd-immunity may be problematic, as the complications and long-term sequelae are not to be taken lightly. It seems that even minor infections with this virus can cause long-term consequences in lung scarring, brain injury, immune dysfunction, heart inflammation, metaplasia and maybe even future potential of carcinogenesis. The only proven advice right now is still "distancing" and personal protection equipment.
The official answer as of July 10, 2020:
Here is how and why the vaccine is slow: A modified quote from JAMA today July 10, 2020:
Prevention and Vaccine Development COVID-19 is a potentially preventable disease. The relationship between the intensity of public health action and the control of transmission is clear from the epidemiology of infection around the world.25,101,102 However, because most countries have implemented multiple infection control measures, it is difficult to determine the relative benefit of each.103,104 This question is increasingly important because continued interventions will be required until effective vaccines or treatments become available. In general, these interventions can be divided into those consisting of personal actions (eg, physical distancing, personal hygiene, and use of protective equipment), case and contact identification (eg, test trace-track-isolate, reactive school or workplace closure), regulatory actions (eg, governmental limits on sizes of gatherings or business capacity; stay-at-home orders; proactive school, workplace, and public transport closure or restriction; cordon sanitaire or internal border closures), and international border measures (eg, border closure or enforced quarantine). A key priority is to identify the combination of measures that minimizes societal and economic disruption while adequately controlling infection. Optimal measures may vary between countries based on resource limitations, geography (eg, island nations and international border measures), population, and political factors (eg, health literacy, trust in government, cultural and linguistic diversity). The evidence underlying these public health interventions has not changed since the 1918 flu pandemic.105 Mathematical modeling studies and empirical evidence support that public health interventions, including home quarantine after infection, restricting mass gatherings, travel restrictions, and social distancing, are associated with reduced rates of transmission.101,102,106 Risk of resurgence follows when these interventions are lifted. A human vaccine is currently not available for SARS-CoV-2, but approximately 120 candidates are under development. Approaches include the use of nucleic acids (DNA or RNA), inactivated or live attenuated virus, viral vectors, and recombinant proteins or virus particles.107,108 Challenges to developing an effective vaccine consist of technical barriers (eg, whether S or receptor binding domain proteins provoke more protective antibodies, prior exposure to adenovirus serotype 5 [which impairs immunogenicity in the viral vector vaccine], need for adjuvant), feasibility of largescale production and regulation (eg, ensuring safety and effectiveness), and legal barriers (eg, technology transfer and licensure agreements). The SARS-CoV-2 S protein appears to be a promising immunogen for protection, but whether targeting the full-length protein or only the receptor-binding domain is sufficient to prevent transmission remains unclear.108 Other considerations include the potential duration of immunity and thus the number of vaccine doses. Coronavirus Disease 2019 (COVID-19)—Epidemiology, Diagnosis, and Treatment Review Clinical Review & Education jama.com (Reprinted) JAMA Published online July 10, 2020 E9 © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by Gary Ordog on 07/10/2020 needed to confer immunity. More than a dozen candidate SARSCoV-2 vaccines are currently being tested in phase 1-3 trials. Other approaches to prevention are likely to emerge in the coming months, including monoclonal antibodies, hyperimmune globulin, and convalescent titer. If proved effective, these approaches could be used in high-risk individuals, including health care workers, other essential workers, and older adults (particularly those in nursing homes or long-term care facilities). Thank you and stay safe; Gary Ordog, MD
White House USA Dr. Brix statement on the vaccine in the USA on September 03, 2020:
NIH Director statement at todays (September 09, 2020) Vaccine Hearings in the USA. Alleging "Science over Politics."
September 16, 2020: Some possible early answers in the news today:
Pfizer reports 'potential' of COVID-19 candidate vaccine after expanding trial to 44,000 people
Karen Weintraub, USA TODAY
Pfizer, one of the front-runners in the quest for a COVID-19 vaccine, said its candidate vaccine looks safe, and the company expects to have data next month on how well it protects people against the coronavirus.
Pfizer CEO Albert Bourla said Tuesday that he is intentionally revealing more information about the COVID-19 candidate vaccine than he would about any other vaccine under development, because he wants the process to be open and transparent.
"Transparency is a must, particularly given this situation and the politicization of the vaccine," he said in a Q&A with journalists.
The company said Saturday that it was expanding its trial from 30,000 to 44,000 people to include teenagers, ages 16-18, as well as people with diseases such as HIV and hepatitis A, B or C. Tuesday, Bourla said the expansion took place because the vaccine appeared to be extremely safe, and the trial could be expanded without delaying the timeline for completion. The first patient enrolled in Pfizer's COVID-19 vaccine clinical trial at the University of Maryland School of Medicine in Baltimore receives an injection May 4.
Warp speed? Why a coronavirus vaccine is more than a year away, despite medical researchers' progress
In data released Tuesday, the company showed that participants – both younger people and senior citizens – complained of only minor side effects, such as headaches and sore arms. The data included about 6,000 people; some who received the active vaccine and others the placebo. The company – which is developing its vaccine, called BNT162, in collaboration with German vaccine developer BioNTech – does not know which participant got which.
An independent Data Safety Commission does know who got the active vaccine and has been checking regularly to make sure there are no health concerns, Pfizer executives said.
There probably have been some serious health issues during the trial, but the safety panel "concluded that none are vaccine-related," said Kathrin Jansen, Pfizer senior vice president and head of vaccine research and development.
The larger numbers should allow the company to look more closely at subgroups of participants, such as those with underlying health conditions such as HIV, and those who had the virus when they received the vaccine, she said.
A final report on the safety and effectiveness of the vaccine should be ready for regulators to review next month.
'It's not at all unprecedented': AstraZeneca's COVID-19 vaccine trial stopped after illness
The vaccine must be at least 50% effective – protecting on average at least half the people who take it – for it to win federal approval and be given to the public. Pfizer manufactures BNT162 in three plants in the USA – in Kalamazoo, Michigan; St. Louis; and Andover, Massachusetts – as well as in Germany and Belgium.
It is not clear how long the vaccine's protection will last. The company is preparing for three possibilities: that people will need an annual shot, as with the flu; that they will need a vaccine every few years, as with tetanus; or that it will be one-and-done, like the polio vaccine, said Dr. Mikael Dolsten, the company's chief scientific officer.
"We think this vaccine has the potential to give reasonable and good protection, but we need to monitor [it]," Dolsten said. "It's reasonable also to assume that we need maybe in the future a boost, because this is a real pandemic and there's going to be a lot of virus circulating even after global [vaccination] campaigns."
Jansen said that although Pfizer is committed to and "very happy with its current vaccine candidate," the company is already working on a second generation.
Pfizer hopes to make two improvements in the next generation, she said: eliminating the need to keep the vaccine frozen and altering the technology so only one dose will be needed, instead of two.
BNT162 uses technology called messenger RNA, which trains the person's cells to make a protein on the surface of the coronavirus that causes COVID-19. Once the immune system learns to recognize this protein, it will attack when it sees it again on the virus.
Achieving herd immunity: How vaccines and masks are the keys to fight coronavirus
In a next-generation vaccine, Jansen said, she could envision a messenger RNA that could amplify itself. "There may be an opportunity that with such an approach, you would be able to only need a single shot" that would provide both "the priming and the boosting effect."
The vaccine needs to be kept frozen at minus-80 degrees, the temperature of dry ice. Pfizer ships BNT162 in coolers that maintain the ultra-cold temperature. The cooler can be fed with dry ice to keep the vaccine frozen for 15 days, then it can be refrigerated for up to five more days before being diluted and injected, said Angela Hwang, president of the Pfizer Biopharmaceuticals Group.
Because the company expects high demand for the vaccine, and its shipping network is efficient, Hwang said the vaccine shouldn't suffer heat damage. "No dose is going to be lying around for very long," she said.
A second-generation vaccine that did not require such cold conditions would be an improvement, Dolsten said.
Bourla, speaking at the end of a two-day conference for investors, bemoaned the politicization of COVID-19 vaccine and drug development.
But he said he thinks the pharmaceutical industry is "rising to the occasion" of the pandemic and hopes that will boost the industry's public image.
"I don't want to declare any victory, just because we're going to bring a vaccine or a treatment that works, that we're going to come back to where we deserve to be, but I think it will be a very good step," he said. "Then we need to continue doing the right thing."
He had one concluding thought as he ended the Q&A: "Science will win," he said.
Thank you and stay safe; Gary Ordog, MD September 16, 2020.
This is the best succinct statement have seen on this topic, and I would like to quote Dr. Mahima Lall (in a comment on RG here): " ... vaccine development occurs step by step. The first step is to identify what type of immune response would neutralize the virus. This would require identifying the most antigenic epitope which would evoke an immune response which is protective. The designing of this has to be done with a backbone of some other virus which has the capacity to fit in these antigenic proteins of the virus against which the vaccine is being created. It may be Adenovirus vector or some other virus. The vaccine has to undergo testing on an animal model. then efficacy must be checked, is it able to perform what it intends to. And does it have side effects. It has to be tested on a small group of humans followed by a larger cohort and all this is done as Phases. Every vaccine that is developed has to undergo Phase 1, phase 2, phase 3 and finally phase 4 trials. Even fast tracking the entire sequence would take time. As safety always comes first and the vaccine should do no harm." Thank you for making this statement.
Here is an update on why the vaccine is so difficult. Note that they are saying that multiple vaccinations will be required for COVID-19 alone!!
OCTOBER 14, 2020
Review sums up current knowledge about SARS-CoV-2 immunity, application to vaccine development
In a review published in The Lancet, researchers discussed what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their application to the coronavirus disease 2019 (COVID-19) vaccines currently in phase 3 clinical trials, based on a search performed on PubMed for articles published up till September 24, 2020.
“There is little knowledge of post-infection immunity to SARS-CoV-2, and the biological and genetic factors responsible for the broad spectrum of disease severity remain unclear. Data suggest that uncoordinated or partially neutralizing antibodies, and responses from CD4+ and CD8+ T cells, might be associated with COVID-19 severity, with age being a risk factor,” wrote Gregory A Poland, MD, Mayo Clinic, Rochester, Minnesota, and colleagues.
“Information concerning the durability of immunity to SARS-CoV-2 infection, and the targets of B-cell and T-cell responses, can assist in the continued development of succeeding generations of new vaccines and therapeutics,” they added.
Humoral immunity to SARS-CoV-2
The authors said most patients with COVID-19 or those who are convalescent have virus-specific IgM, IgA, and IgG responses in the days after infection, suggesting that antibodies mediate protective immunity to SARS-CoV-2. The overall kinetics of the antibody response against SARS-CoV-2 are analogous to those for SARS-CoV-1, which are characterized by robust seroconversion (IgM and IgG) 7–14 days following symptom onset and antibody concentrations persisting for weeks to months after infection and viral clearance.
“Additional longitudinal studies are necessary to further understand the dynamics of SARS-CoV-2-induced antibodies in populations and the role that these antibodies have in the risk and severity of COVID-19. Such knowledge is relevant to diagnosing patients with COVID-19 early and for examining the incidence of infections (clinical and subclinical) in different populations. It is important to understand whether, and how, other factors (eg, age, race, ethnicity, sex, body-mass index, and smoking status) might influence serological and immune responses during SARS-CoV-2 infection,” the authors wrote.
Cellular immunity to SARS-CoV-2
According to the authors, initial reports on cellular immunity to SARS-CoV-2 have consisted of case reports with small numbers of patients, which have indicated that the proportion of CD38+ , HLA-DR+ T cells (both CD4+ and CD8+) increases during the first 7–10 days of COVID-19 symptoms and begins to return to baseline around day 20. In addition, SARS-CoV-2- specific T cells express perforin 1 and granzymes upon in vitro re-stimulation with viral antigens. Meanwhile, in some reports but not others, the increase in the proportion of SARS-CoV-2-specific T cells seemed to correlate with disease severity. “This finding represents an important unanswered question that could affect vaccine development,” the authors said. “Serious illness has also been linked to a greater reduction in peripheral CD4+ and CD8+ T cell counts compared with non-serious illness, suggesting a link between disease severity and the size of the cellular immune response; however, larger studies are necessary to further support a correlation.”
Overall, the current data show that both CD4+ T-cell and CD8+ T-cell responses occur in most patients infected by SARS-CoV-2 within 1–2 weeks after symptom onset and produce mainly Th1 cytokines. The frequency of CD4+ T cells targeted to the spike glycoprotein correlates with neutralizing antibody titers, suggesting that the T-cell response might also vary among individuals with different disease severities.
The authors noted that the contribution of cellular immunity to protection against COVID-19 is not currently clear; however, a balanced immune response consisting of high titers of neutralizing antibodies and Th1-biased T cells will probably be optimal. The role of CD8+ T-cell responses in protection against COVID-19 is also unclear, with some evidence suggesting that CD8+ T-cell responses are stronger in patients with mild disease than in patients with severe disease. Additional research into the cellular immune response to SARS-CoV-2 and COVID-19 vaccines will be necessary to test this hypothesis.
Vaccines against SARS-CoV-2
Various candidate vaccines are being developed and tested, including nucleic acid vaccines, inactivated virus vaccines, live attenuated vaccines, protein or peptide subunit vaccines, and viral-vectored vaccines. According to the authors, the front runner candidates are all administered by the intramuscular route. “Therefore, focus is on evaluating immune responses in the blood rather than those in the mucosal surfaces. The role of mucosal immunity should not be discounted, and several intranasal vaccine formulations are under investigation,” they added.
Vaccine candidates currently in phase 3 trials include a chimpanzee adenovirus (ChAdOx1/AXD1222) vaccine, mRNA-based vaccines (mRNA-1273, BNT162b1, BNT162b2), adenovirus serotype 26 vector (Ad26.COV2.S), adenovirus serotype 5 vector and adenovirus serotype 26 vector (Sputnik V), adenovirus serotype 5 vector (Ad5CoV), inactivated virus vaccines (CoronaVac, BBIBP-CorV).
“Much remains to be learned regarding coronavirus immunity in general and SARS-CoV-2 immunity in particular, including the protective immunity induced by vaccines and the maintenance of immunity against this virus. Furthermore, multiple vaccine types will probably be needed across different populations (eg, immune-immature infants, children, pregnant women, immuno-compromised individuals, and immunosenescent individuals aged ≥65 years),” the authors noted.
“In addition to the adaptive immune response, there are some data suggesting that trained innate immunity might also have a role in protection against COVID-19. Multiple clinical trials are examining whether unrelated vaccines, such as the measles, mumps, and rubella vaccine and the Bacillus Calmette–Guérin vaccine, can elicit trained innate immunity and confer protection against COVID-19,” the authors said. “It is crucial that research focuses on understanding the genetic drivers of infection and vaccine induced humoral and cellular immunity to SARS-CoV-2, defining detailed targets of humoral and cellular immune responses at the epitope level, characterizing the B-cell receptor and T-cell receptor repertoire elicited by infection or vaccination, and establishing the long-term durability, and maintenance, of protective immunity after infection or vaccination.”
Reference: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32137-1/fulltextSOURCE: The Lancet
Multiple vaccines will be required! Until then, please stay safe.
Thank you October 14, 2020; Gary Joseph Ordog, MD.
Last night on the news, it sounded as if they were nearer to finding something effective:
https://www.bbc.co.uk/news/uk-54882091