WHO Information Notice for IVD Users 2020/05

WHO Information Notice for IVD Users 2020/05 Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2 20 January 2021 Medical product alert Geneva Reading time: 1 min (370 words) Français Español Product type: Nucleic acid testing (NAT) technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2 Date: 13 January 2021 WHO-identifier: 2020/5, version 2 Target audience: laboratory professionals and users of IVDs. Purpose of this notice: clarify information previously provided by WHO. This notice supersedes WHO Information Notice for In Vitro Diagnostic Medical Device (IVD) Users 2020/05 version 1, issued 14 December 2020. Description of the problem: WHO requests users to follow the instructions for use (IFU) when interpreting results for specimens tested using PCR methodology. Users of IVDs must read and follow the IFU carefully to determine if manual adjustment of the PCR positivity threshold is recommended by the manufacturer. WHO guidance Diagnostic testing for SARS-CoV-2 states that careful interpretation of weak positive results is needed (1). The cycle threshold (Ct) needed to detect virus is inversely proportional to the patient’s viral load. Where test results do not correspond with the clinical presentation, a new specimen should be taken and retested using the same or different NAT technology. WHO reminds IVD users that disease prevalence alters the predictive value of test results; as disease prevalence decreases, the risk of false positive increases (2). This means that the probability that a person who has a positive result (SARS-CoV-2 detected) is truly infected with SARS-CoV-2 decreases as prevalence decreases, irrespective of the claimed specificity. Most PCR assays are indicated as an aid for diagnosis, therefore, health care providers must consider any result in combination with timing of sampling, specimen type, assay specifics, clinical observations, patient history, confirmed status of any contacts, and epidemiological information. Actions to be taken by IVD users: Please read carefully the IFU in its entirety. Contact your local representative if there is any aspect of the IFU that is unclear to you. Check the IFU for each incoming consignment to detect any changes to the IFU. Provide the Ct value in the report to the requesting health care provider. Contact person for further information: Anita SANDS, Regulation and Prequalification, World Health Organization, e-mail: rapidalert@who.int References: 1. Diagnostic testing for SARS-CoV-2. Geneva: World Health Organization; 2020, WHO reference number WHO/2019-nCoV/laboratory/2020.6. 2. Altman DG, Bland JM. Diagnostic tests 2: Predictive values. BMJ. 1994 Jul 9;309(6947):102. doi: 10.1136/bmj.309.6947.102.

ΑΝΟΣΙΑ ΑΓΕΛΗΣ (HERD IMMUNITY)

***** Απο που προκυπτει το 25%-40% της ανοσιας αγελης ... 1. Herd immunity thresholds for SARS-CoV-2 estimated from unfolding epidemics. "Our inferences result in herd immunity thresholds around 10-20%, considerably lower than the minimum coverage needed to interrupt transmission by random vaccination, which for R0 higher than 2.5 is estimated above 60%." https://www.medrxiv.org/con.../10.1101/2020.07.23.20160762v3 2.A New Understanding of Herd Immunity The portion of the population that needs to get sick is not fixed. We can change it. “We just keep running the models, and it keeps coming back at less than 20 percent,” Gomes said. “It’s very striking.” "If that proves correct, it would be life-altering news. It wouldn’t mean that the virus is gone. But by Gomes’s estimates, if roughly one out of every five people in a given population is immune to the virus, that seems to be enough to slow its spread to a level where each infectious person is infecting an average of less than one other person. The number of infections would steadily decline. That’s the classic definition of herd immunity. It would mean, for instance, that at 25 percent antibody prevalence, New York City could continue its careful reopening without fear of another major surge in cases. " https://www.theatlantic.com/.../herd-immunity.../614035/ Οποιος θελει διαβαζει τις ερευνες, οποιος θελει διαβαζει τα αρθρα... ****** Απο που προκυπτει οτι η D3, και οχι μονο, ειναι εργαλειο ανοσοποιησης ?? 3. The immunological implication of the new vitamin D metabolism. "Vitamin D is a neuro-hormone regulating calcium-phosphate homeostasis, cell proliferation, and immunomodulation. Active hormone produced by brain and immune cells mediates immune system response; lung calcitriol is involved in fighting respiratory tract infections; finally, prostate and placenta vitamin D regulates cells growth and proliferation within such tissues. Immune modulation by vitamin D includes enhancing innate immune response, attenuating and stimulating Th1 and Th2 cell proliferation, respectively, and promoting self-tolerance. Hypovitaminosis D is a common finding in several autoimmune diseases." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305614/ 4. Can Vitamin D Lower Your Risk of COVID-19? "Having healthy vitamin D levels can enhance immune health and may be helpful in people with COVID-19." https://www.healthline.com/nutri.../vitamin-d-coronavirus... Οποιος θελει διαβαζει τις ερευνες, οποιος θελει διαβαζει τα αρθρα... ***** Για τον Ψευδαργυρο ? 5. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19 Amit Kumar, Yuichi Kubota,⁎ Mikhail Chernov, and Hidetoshi Kasuya Administration of Zn supplement has a potential to enhance antiviral immunity, both innate and humoral, and to restore depleted immune cell function or to improve normal immune cell function, in particular in immunocompromised or elderly patients. Zn may also act in a synergistic manner when co-administered with the standard antiviral therapy, as was demonstrated in patients with hepatitis C, HIV, and SARS-CoV-1. Effectiveness of Zn against a number of viral species is mainly realized through the physical processes, such as virus attachment, infection, and uncoating. Zn may also protect or stabilize the cell membrane which could contribute to blocking of the virus entry into the cell. On the other hand, it was demonstrated that Zn may inhibit viral replication by alteration of the proteolytic processing of replicase polyproteins and RNA-dependent RNA polymerase (RdRp) in rhinoviruses, HCV, and influenza virus, and diminish the RNA-synthesizing activity of nidoviruses, for which SARS-CoV-2 belongs. Therefore, it may be hypothesized that Zn supplementation may be of potential benefit for prophylaxis and treatment of COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247509/ Για λιγο περισσοτερη κατανοηση του Ψευδαργυρου δειτε το παρακατω: 6. Zinc and SARS‑CoV‑2: A molecular modeling study of Zn interactions with RNA‑dependent RNA‑polymerase and 3C‑like proteinase enzymes " Zn is recommended by the National Institutes of Health (NIH) for inducing the immune system and preventing viral infections; however, the amount of Zn people requires each day depends on age (74). While Zn supplementation is necessary to correct any deficiency, an overabundance of Zn can also lead to a variety of physiological dysfunctions. Excess Zn can lead to copper deficiency, alter lymphocyte response and inhibit T-cell function (75). Therefore, the use of Zn for therapeutic purposes should still be monitored based on food intake and use of supplements. Although Zn is relatively non-toxic to humans with an median lethal dose of 3 g/kg weight, extreme excess Zn (>100-300 mg/day) should be avoided; the NIH considers 40 mg of zinc a day for adults and 4 mg of zinc a day for infants under 6 months to be the upper limit dose (75)." και αυτο για να ισορροπουν και καποιοι αρνητες ... ναι θελει διελευκανση το πως εχει τετοια αποτελεσματικοτητα ο Ψευδαργυρος. "Most people obtain their daily required Zn through a healthy diet. However, the dietary oral intake supplements of 15-25 mg Zn tablets per day is recommended to help aid immune response in the short term (4). Currently, there is no consensus that Zn is helpful for the prevention and treatment of COVID-19 infection. However, the present bioinformatics and molecular modeling analysis supported the hypothesis that Zn would bind and regulate the enzymatic activities of 3CLpro and RdRp of SARS-CoV-2 and thus inhibit viral replication." https://www.spandidos-publications.com/10.../ijmm.2020.4790 BONUS material : Απο το 2005 στο Virology Journal του FAUCI ... εχει δημοσιευτει το αρθρο για την αποτελεσματικοτητα της ΧΛΩΡΟΚΙΝΗΣ (+Ψευδαργυρου ΠΡΟΦΑΝΩΣ) απεναντι στους Κορονοιους και μαλιστα στον SARS-CoV-1 τον αδελφο του SARS-CoV-2... Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. https://virologyj.biomedcentral.com/.../1743-422X-2-69 Ο FAUCI ξερει απο το 2005 και πιο πριν θα πω εγω οτι ο Ψευδαργυρος σταματαει τον πολλαπλασιασμο των ιων CoV και του HIV που ειναι της ιδιας συνομοταξιας και χρησιμοποιουν τα ιδια ενζυμα, με τον δευτερο να εχει και περισσοτερους μηχανισμους !! Περαν αυτου απο το 1950 οι ερευνες εχουν αποδειξει επανειλημμενα οτι ο Ψευδαργρυρος ειναι πανισχυρο αντιικο στοιχειο απεναντι σε RNA μονης αλυσιδας + sense ιους !! γιατι κλειδωνει το ενζυμο πολλαπλασιασμου τους το RdRP !! https://www.medrxiv.org/content/10.1101/2020.07.23.20160762v3?fbclid=IwAR25SqDX3WHRPHaY0S5sf5TBs2BPHJHJ-HdcB8aRYeCfWZh9ss9PQR0Gk9I

COVID-19: Rethinking the Lockdown Groupthink

Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the Coronavirus Disease 2019 (COVID-19) worldwide pandemic in 2020. In response, most countries in the world implemented lockdowns, restricting their population’s movements, work, education, gatherings, and general activities in attempt to ‘flatten the curve’ of COVID-19 cases. The public health goal of lockdowns was to save the population from COVID-19 cases and deaths, and to prevent overwhelming health care systems with COVID-19 patients. In this narrative review I explain why I changed my mind about supporting lockdowns. First, I explain how the initial modeling predictions induced fear and crowd-effects [i.e., groupthink]. Second, I summarize important information that has emerged relevant to the modeling, including about infection fatality rate, high-risk groups, herd immunity thresholds, and exit strategies. Third, I describe how reality started sinking in, with information on significant collateral damage due to the response to the pandemic, and information placing the number of deaths in context and perspective. Fourth, I present a cost-benefit analysis of the response to COVID-19 that finds lockdowns are far more harmful to public health than COVID-19 can be. Controversies and objections about the main points made are considered and addressed. I close with some suggestions for moving forward. https://www.preprints.org/manuscript/202010.0330/v2

Σκάνδαλο στη Γερμανία! Τεστ PCR... ένα ακριβοπληρωμένο σκουπίδι!

Ένα μεγάλο σκάνδαλο ξεσπάει στην Γερμανία, αλλά και σε ολόκληρο τον κόσμο, μετά την δημοσίευση συμπερασμάτων 23 διεθνών ιολόγων, μικροβιολόγων και σχετικών επιστημόνων, που αποδεικνύουν ότι... όλα τα τεστ PCR, σε πραγματικό χρόνο (RT-PCR) βγαίνουν "ΨΕΥΔΩΣ ΘΕΤΙΚΑ"! (Έκθεση Μπόργκερ). Σ΄αυτά τα τεστ βασίστηκε όλη η πολιτική "αντιμετώπισης της πανδημίας". Οι έρευνες, οι δρακόντιες επιστημονικές συμβουλές, για οικονομικά λοκντάουν, για πρόστιμα, ξύλο, συλλήψεις, κοινωνική αποστασιοποίηση. Το σκάνδαλο περιλαμβάνει τον ας τον πούμε "Τσιόδρα της Γερμανίας", επικεφαλής της συμβουλευτικής ομάδας της Μέρκελ, για τον ιό, δόκτωρα Κρίστιαν Ντρόστεν. Από τις 23 Ιανουαρίου του 2020, όταν οι θάνατοι, στην Κίνα, έφταναν μόλις τους 6 νεκρούς, ο Ντρόστεν με αρκετούς συναδέλφους του, στο Ινστιντούτο Ιολογίας του Νοσοκομείου "Σαριτέ", καθώς και με τον επικεφαλής μιας μικρής εταιρίας βιοτεχνολογίας στο Βερολίνο , την "TIB Molbiol Syntheselabor GmbH" δημοσίευσε μία μελέτη, στο επιστημονικό περιοδικό "Eurosurveillance" , του Κέντρου Πρόληψης και Ελέγχου Νόσων της ΕΕ. Το άρθρο είχε τίτλο "Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR" (Eurosurveillance 25 (8) 2020). Ο Ντρόστεν και η ομάδα του ισχυρίζονταν ότι ανέπτυξαν την πρώτη αποτελεσματική δοκιμή, για την ανίχνευση του ιού. Τα νέα χαιρετίστηκαν με άμεση έγκριση του τεστ, από τον διεφθαρμένο Γενικό Διευθυντή του Παγκόσμιου Οργανισμού Υγείας, του ΜΟΝΟΥ μη γιατρού επικεφαλής, Τέντρο Ανχάνομ. Το ίδιο έκανε και η Μέρκελ. Έκτοτε, το τεστ, που υποστηρίζεται από τον Ντρόστεν για τον ιό, έχει εξαπλωθεί μέσω του ΠΟΥ σε όλο τον κόσμο, ως το πιο χρησιμοποιούμενο πρωτόκολλο δοκιμών για να προσδιορίσει εάν ένα άτομο μπορεί να έχει COVID-19. Η πρώτη κίνηση που έκαναν οι 23 επιστήμονες, στις 27 Νοεμβρίου, μετά από μελέτες, ήταν να ζητήσουν από το επιστημονικό περιοδικό, την απόσυρση του "πονήματος" Ντρόστεν, κατηγορώντας αυτόν και την ομάδα του, για "θανατηφόρα" επιστημονική ανικανότητα και ελαττώματα στην προώθηση των τεστ. "Το έγγραφο Corman-Drosten υποβλήθηκε στην Eurosurveillance στις 21 Ιανουαρίου 2020 και έγινε δεκτό για δημοσίευση στις 22 Ιανουαρίου 2020. Στις 23 Ιανουαρίου 2020 το έγγραφο ήταν online." τονίζουν οι επιστήμονες. Και μάλιστα, το πρωτόκολλο δοκιμής του Ντρόστεν είχε αποσταλεί και υιοθετηθεί, από τον ΠΟΥ, ως παγκόσμιο τεστ, που επιβεβαιώνει την ύπαρξη του ιού, στις 17 Ιανουαρίου, ΠΡΙΝ ΚΑΝ ΔΗΜΟΣΙΕΥΤΕΙ, στο επιστημονικό περιοδικό! Τόσο ο Ντρόστεν, όσο και ο συν-συγγραφέας της "έρευνας" δεν αποκάλυψαν, ούτε την σύγκρουση συμφερόντων, που υπήρχε. Ήταν και οι δύο μέλη της συντακτικής ομάδας του επιστημονικού περιοδικού. Ένα ακόμη μέλος της ομάδας του Ντρόστεν, που έδωσε μια κάλυψη φαινομενικής αξιοπιστίας του τεστ, ήταν ο Ολφερτ Λάντ, επικεφαλής της εταιρίας "Tib-Molbiol", στο Βερολίνο, που ανέλαβε την παραγωγή των τεστ και που ούτε κι αυτός αποκάλυψε την δεύτερη ιδιότητα του. Ο ίδιος ο Ντρόστεν και οι επικεφαλής, στο Πανεπιστήμιο Goethe της Φρανκφούρτης, όπου ισχυρίζεται ότι έλαβε το διδακτορικό του το 2003, κατηγορούνται για απάτη πτυχίου. Ο Δρ Markus Kühbacher, ένας ειδικός που διερευνά την επιστημονική απάτη όπως και τις λογοτεχνικές διατριβές, κατηγορεί το Πανεπιστήμιο, για συγκάλυψη μιας διατριβής που ουδέποτε είχε κατατεθεί και έπρεπε να υπάρχει σε τρία αντίτυπα. Τα δύο αντίγραφα "εξαφανίστηκαν" και το τρίτο και μοναδικό έχει υποστεί ζημιά, από το νερό! Ο Ντρόστεν θ΄αντιμετωπίσει κατηγορία, για κατοχή ψευδούς διδακτορικού τίτλου. Με απλά λόγια, όλο το οικοδόμημα του Ιδρύματος Γκέιτζ, της κυβέρνησης Μέρκελ, του ΠΟΥ και του Παγκόσμιου Οργανισμού Φαρμάκων(WEF), όπως και τα μη δοκιμασμένα εμβόλια, στηρίχθηκαν στ΄αποτελέσματα ενός τεστ PCR, που δεν είναι τίποτα παραπάνω από ένα ακριβοπληρωμένο σκουπίδι! Επισυνάπτω την μελέτη των 23 επιστημόνων: https://cormandrostenreview.com/report/?fbclid=IwAR1TzeLoq3mpuJUmealJhSCaeNyEYAyp8qX1gIDCs3MgLWkdy56LCyovv28

Covid-19: Vaccine trials need more transparency to enable scrutiny and earn public trust, say experts

Eleven covid-19 vaccine candidates are in phase III clinical trials. But while the scientists involved have been praised for their speed, others are calling for more transparency to ensure studies are robust and the evidence is sound. Elisabeth Mahase reports “These are unprecedented times and these are unprecedented clinical trials . . . This can’t be business as usual,” says Jason Schwartz, assistant professor of public health at Yale School of Public Health. Schwartz says that transparency is crucial to ensure that the scientific community can review and scrutinise the work but also to build public understanding and confidence in the much anticipated potential covid-19 vaccines. However, not all transparency is equal, he adds. “It needs to be the kind of transparency that isn’t filtered through corporate press releases or statements to investors, or a kind of pseudo-transparency in which the manufacturers are trying to massage or control the message. [It needs to be] real transparency in terms of the kinds of documents and materials that can help the public, and especially the broader scientific community, both understand the design of these trials and ultimately understand how to interpret the results from them.” Show your working A key document to understanding how trials are being run is the study protocol. After pressure from scientists and public health experts, four major protocols of covid vaccine trials have now been made public. These include AstraZeneca’s halted US study of the University of Oxford’s AZD1222 vaccine candidate,1 the Pfizer and BioNTech study of their BNT162b,2 Moderna’s study of its mRNA-1273,3 and the Johnson & Johnson Ad26.COV2.S.4 Additionally, the Oxford team has published the information sheets provided to trial participants,5 a move towards transparency that other companies seem not to have followed. Moderna, Pfizer, and BioNTech did not respond to several BMJ requests for the informed consent forms or offer an explanation as to why they would not publish them. Schwartz credits those trial sponsors that have listened. “The release of the protocols was really important and, as far as I know, an unprecedented step so early in the conduct of the trial . . . The consent documents are certainly important to help us understand the ethics of these trials and help understand how the research subjects are being informed about their participation and the risks and benefits of it.” However, he added that there was plenty more that could be shared in the form of real objective documents about plans, relationships, and scientific standards. Schwartz has called for trial sponsors to share these raw materials to “help the scientific community understand the work that’s ongoing and help the public understand what is usually a process that rarely gets this kind of widespread scrutiny.” Who has oversight? One key area that Schwartz is interested in relates to the independent boards that review the data from these clinical trials. “These data and safety monitoring boards [DSMBs] will be undertaking those interim reviews of the trials and potentially stopping the trial because the evidence is so favourable or, conversely, the evidence is so unfavourable or there’s a serious safety issue. DSMBs are so important, particularly if these vaccines get an expedited review and potential authorisation here in the US by the Food and Drug Administration,” he explains. Despite the importance of the DSMBs, little is known about their standards. “There’s more we can learn about the groups and their approaches [and] plans, since that seems to be a really important lever,” says Schwartz. In the US a joint DSMB has been formed to review unblinded data from several trials being run in the country, including the Moderna, Johnson & Johnson, and AstraZeneca trials, but not Pfizer’s. Although the identity of the board’s 10-15 members has mostly remained confidential, the chair—appointed by the director of the National Institute of Allergy and Infectious Diseases, Anthony Fauci—has been revealed as Richard Whitley. Whitley is a professor of paediatrics and co-division director of paediatric infectious diseases at the University of Alabama. He also sits on the board of directors of the drug company Gilead, for which he was paid roughly $430 000 in 2019.6 The bioethicist Charles Weijer, who specialises in the ethics of health related randomised controlled trials at Western University, Ontario, thinks the entire membership of these DSMBs should be made public. “Public confidence in judgments [made by these groups] will be enhanced by knowing that committee members possess requisite expertise and have no relevant conflicts of interest. While this is not usual practice in clinical trials, this step is required to bolster public trust in covid-19 vaccine research.” Weijer receives consulting income from the drug company Eli Lilly. Schwartz would also like to see more information made public on the contractual agreements between manufacturers and their government sponsors. “[These agreements] have been shielded from public view, and I think that’s detrimental to understanding the nature of these relationships and partnerships,” he says. Ending trials early A key role that DSMBs could play is in stopping vaccine trials early. Fauci, who advises the White House on covid-19, has said this can happen if the boards decide the data are good and a vaccine is safe and effective. He emphasised that those making such a decision “better be sure” that the evidence was good but said there would be a “moral obligation” to get the vaccine to the public earlier if it really was safe and effective.7 At this point, Schwartz says transparency will be crucial. “The real critical moment and opportunity for transparency will be when we get to the point where decisions by regulatory bodies are going to be made based on the products in these trials. And I think that’s where the light will and should shine, with even greater focus.” Being transparent about how such a decision is made will be even more important given the unease that has built up that a vaccine might be approved prematurely. Concerns have grown over potential political pressure to rush out a vaccine before the science is clear since comments made by Donald Trump, in which he hinted that a vaccine could be made available before the 3 November presidential election.8 This seemed to have prompted the heads of nine drug companies—AstraZeneca, BioNTech, GlaxoSmithKline, Johnson & Johnson, Merck/MSD, Moderna, Novavax, Pfizer, and Sanofi—to sign an open letter committing to submit for approval or emergency use authorisation only after “demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as FDA [the US Food and Drug Administration].”9 And in early October the FDA published new guidance stating that it would require at least two months of follow-up data after trial participants received all doses of a vaccine, leading many people to conclude that a so called “October surprise” was no longer possible.10 But Weijer thinks that those responsible should go further and publicly confirm that they will not end trials early if they get a positive efficacy signal during interim analysis. “We really need safety information on the full planned sample size in order to give us the sort of good grounds to believe not only that a vaccine works but, crucially, that it’s safe,” he says. “We’re going to be giving this vaccine to hundreds of millions of healthy people. To be able to reliably detect a very rare adverse event which is associated with the vaccine—so that’s something that occurs in one in 10 000 people—you need safety data on 60 000 people,” he says. The importance of ensuring that vaccines are not rushed out is something emphasised by experts from the UK Royal Society’s DELVE (Data Evaluation and Learning for Viral Epidemics) initiative,11 which has published a report on the development and implementation of covid-19 vaccines.12 “If vaccines were deployed outside clinical trials before safety and efficacy have been fully established and prove to be ineffective or cause rare but severe side effects during the larger-scale roll-out, they could cause substantial harm and damage public confidence in other vaccines,” DELVE warned. The DELVE team also highlighted the importance of transparency when it comes to the limitations of any vaccine: “Clear, transparent communication can be used to address rational doubts and to enable informed decision-making . . . it should not hide the potential limitations of vaccines including possible limited availability, incomplete protection requiring boosting, and reactogenicity.” The report says that although “negative or complicating factors might lower uptake, their discovery post-rollout is likely to have a far greater negative impact on uptake.” Trial transparency gone awry In September the University of Oxford and AstraZeneca’s vaccine candidate made headlines after the trials were paused around the world (including in the US, UK, Japan, India, Brazil, and South Africa) while an investigation was carried out into a “single event of an unexplained illness.” Experts have made it clear that pauses in vaccine trials are common and a sign that the trial’s oversight process is working.13 While this was the first time a pause of the trial had been announced, it was not actually the first time it had been halted. The patient information sheet from 12 July shows that it was paused earlier in the year after one trial volunteer developed symptoms of transverse myelitis.14 But bioethicist Charles Weijer of Western University, Ontario, told The BMJ that the disclosure of the serious adverse events in the Oxford trial patient information sheet “is not, in my view, adequate.” When he compared different versions of the sheet,15 he noted that while transverse myelitis was initially mentioned, this was then removed and replaced with “vaguer language.” The 11 September version said that volunteers had “developed unexplained neurological symptoms including changed sensation or limb weakness.” It was reported in the media that the second serious adverse event in September may have been transverse myelitis, although this was not confirmed, and that the patient was admitted to hospital as a result. It was then reported that the patient was set to be discharged from hospital, but no further updates have been provided. “Prospective participants are not informed that, if media reports are to be believed, the second case of transverse myelitis was sufficiently severe as to warrant hospital admission,” says Weijer. “Consent documents should contain a clear and accurate description of any serious adverse events. Certainly, they should contain more information than a prospective or current participant could discover with a Google search of the vaccine trial.” The handling of the trial pause has also been criticised in terms of how the information was communicated to the public. “It’s transparency gone awry,” says Jason Schwartz, assistant professor of public health at Yale School of Public Health. “We know we’ve received only very, very fragmentary information about the nature of the events that occurred. Details about what it was were mostly, as I understand it, made public through a call to investors . . . I think there was a failure in terms of how there were just drips of information and uncertainty and missing details to help contextualise what that signal was.” Trials of this vaccine have resumed in Japan, the UK, Brazil, South Africa, and India. Despite this, AstraZeneca’s US based trial has not been restarted, with the Food and Drug Administration recently broadening its safety investigation.16 But this is not the only trial paused because of adverse events. On 12 October Johnson & Johnson announced that it had paused dosing in all its covid-19 vaccine trials while an investigation was carried out into an unexplained illness in a study participant. The company did not seem to be upfront about the issue: the pause was first revealed by the US media outlet STAT.17 It remains to be seen whether lessons from the Oxford and AstraZeneca trial have been learnt. https://www.bmj.com/content/371/bmj.m4042

 

Covid-19 vaccine trials cannot tell us if they will save lives

None of the current trials are designed to detect a reduction in any serious outcome such as hospitalisations, intensive care use, or deaths

Vaccines are being hailed as the solution to the covid-19 pandemic, but the vaccine trials currently underway are not designed to tell us if they will save lives, reports Peter Doshi, Associate Editor at The BMJ today.

Several covid-19 vaccine trials are now in their most advanced (phase 3) stage, but what will it mean exactly when a vaccine is declared “effective”? 

Many may assume that successful phase 3 studies will mean we have a proven way of keeping people from getting very sick and dying from covid-19. And a robust way to interrupt viral transmission.

Yet the current phase 3 trials are not actually set up to prove either, says Doshi. 

“None of the trials currently underway are designed to detect a reduction in any serious outcome such as hospitalisations, intensive care use, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus,” he writes.

He explains that all ongoing phase 3 trials for which details have been released are evaluating mild, not severe, disease - and they will be able to report final results once around 150 participants develop symptoms.

In Pfizer and Moderna’s trials, for example, individuals with only a cough and positive lab test would bring those trials one event closer to their completion.

Yet Doshi argues that vaccine manufacturers have done little to dispel the notion that severe covid-19 was what was being assessed. 

Moderna, for example, called hospitalisations a “key secondary endpoint” in statements to the media. But Tal Zaks, Chief Medical Officer at Moderna, told The BMJ that their trial lacks adequate statistical power to assess that endpoint.

Part of the reason may be numbers, says Doshi. Because most people with symptomatic covid-19 infections experience only mild symptoms, even trials involving 30,000 or more patients would turn up relatively few cases of severe disease. 

“Hospitalisations and deaths from covid-19 are simply too uncommon in the population being studied for an effective vaccine to demonstrate statistically significant differences in a trial of 30,000 people,” he adds. “The same is true regarding whether it can save lives or prevent transmission: the trials are not designed to find out.” 

Zaks confirms that Moderna’s trial will not demonstrate prevention of hospitalisation because the size and duration of the trial would need to be vastly increased to collect the necessary data. “Neither of these I think are acceptable in the current public need for knowing expeditiously that a vaccine works,” he told The BMJ.

Moderna’s trial is designed to find out if the vaccine can prevent covid-19 disease, says Zaks. Like Pfizer and Johnson and Johnson, Moderna has designed its study to detect a relative risk reduction of at least 30% in participants developing lab-confirmed covid-19, consistent with FDA and international guidance.

Zaks also points to influenza vaccines, saying they protect against severe disease better than mild disease. “To Moderna, it’s the same for covid-19: if their vaccine is shown to reduce symptomatic covid-19, they will feel confident it also protects against serious outcomes,” Doshi writes.

But Doshi raises another important issue - that few or perhaps none of the current vaccine trials appear to be designed to find out whether there is a benefit in the elderly, despite their obvious vulnerability to covid-19.

If the frail elderly are not enrolled into vaccine trials in sufficient numbers to determine whether there is a reduction in cases in this population, “there can be little basis for assuming any benefit against hospitalisation or mortality,” he warns.

Doshi says that we still have time to advocate for changes to ensure the ongoing trials address the questions that most need answering.

For example, why children, immunocompromised people, and pregnant women have largely been excluded; whether the right primary endpoint has been chosen; whether safety is being adequately evaluated; and whether gaps in our understanding of how our immune system responds to covid-19 are being addressed.

“The covid-19 vaccine trials may not have been designed with our input, but it is not too late to have our say and adjust their course. With stakes this high, we need all eyes on deck,” he argues.

[Ends]

21/10/2020

Feature: Will covid-19 vaccines save lives? Current trials are not designed to tell us
Journal: The BMJ

Funding: None

Link to Academy of Medical Sciences press release labelling system: https://press.psprings.co.uk/AMSlabels.pdf
Peer reviewed? Yes
Evidence type: Feature
Subjects: Covid-19 vaccine trials

https://www.bmj.com/company/newsroom/covid-19-vaccine-trials-cannot-tell-us-if-they-will-save-lives/?fbclid=IwAR0IQ1AbIzmZDRzYnKIZhKH6ri9U1LaA6N79D4rY3512cBt7oSXfjuvMeUU

DEC 3 Ο Δρ. Wodarg και ο Dr. Yeadon ζητούν διακοπή όλων των μελετών εμβολιασμού του Κορονοιού, Κάλεσμα για να υπογράψετε την ΑΙΤΗΣΗ

 

Ο Δρ. Wodarg και ο Dr. Yeadon ζητούν να σταματήσουν όλες οι μελέτες εμβολιασμού για τον κορονοίο και συνυπογράφουν την αναφορά

2020 ΝΕΑ

Την 1η Δεκεμβρίου 2020, ο πρώην επικεφαλής του τομέα έρευνας αναπνευστικών ασθενειών Dr. Michael Yeadon και ο ειδικός επιδημιολόγος, πνευμονολόγος και πρώην επικεφαλής του τμήματος δημόσιας υγείας Dr. Wolfgang Wodarg υπέβαλαν αίτηση στον EMA, τον Ευρωπαϊκό Οργανισμό Ιατρικής υπεύθυνο για όλη την ΕΕ για την έγκριση φαρμάκων, για την άμεση αναστολή όλων των μελετών εμβολίων SARS CoV 2, ιδίως της μελέτης BioNtech / Pfizer στο BNT162b (αριθμός EudraCT 2020-002641-42).

Ο Dr. Wodarg και ο Dr. Yeadon απαιτούν οι μελέτες - για την προστασία της ζωής και της υγείας των εθελοντών - να μην συνεχιστούν έως ότου υπάρχει διαθέσιμο σχέδιο μελέτης που να είναι κατάλληλο για την αντιμετώπιση των σημαντικών ανησυχιών για την ασφάλεια που εκφράζονται από έναν αυξανόμενο αριθμό γνωστών επιστημόνων κατά του εμβολίου και του σχεδιασμού της μελέτης.

Από τη μία πλευρά, οι αναφέροντες απαιτούν, λόγω της γνωστής έλλειψης ακρίβειας της δοκιμής PCR σε μια σοβαρή μελέτη, πρέπει να χρησιμοποιηθεί η λεγόμενη αλληλουχία Sanger (Sanger sequencing)  . 

Αυτός είναι ο μόνος τρόπος να κάνετε αξιόπιστες δηλώσεις σχετικά με την αποτελεσματικότητα ενός εμβολίου κατά του Covid-19. Βάσει των πολλών διαφορετικών δοκιμών PCR πολύ ποικίλης ποιότητας, ούτε ο κίνδυνος ασθένειας ούτε το πιθανό όφελος του εμβολίου μπορούν να προσδιοριστούν με την απαραίτητη βεβαιότητα, και αυτός είναι ο λόγος για τον οποίο η δοκιμή του εμβολίου στον άνθρωπο είναι ανήθικη.

Επιπλέον, απαιτούν να αποκλειστούν, μπορεί νηα γίνει π.χ. με πειράματα σε ζώα, κίνδυνοι που είναι ήδη γνωστοί από προηγούμενες μελέτες, οι οποίες προέρχονται εν μέρει από τη φύση των κορονοιών. 

Οι ανησυχίες κατευθύνονται συγκεκριμένα στα ακόλουθα σημεία:

Ο σχηματισμός των λεγόμενων ''μη εξουδετερωτικών αντισωμάτων'' ενίσχυση ADE μπορεί να οδηγήσει σε υπερβολική ανοσολογική αντίδραση, ειδικά όταν το εξεταζόμενο πρόσωπο αντιμετωπίζει τον πραγματικό «άγριο» ιό μετά τον εμβολιασμό. 

Αυτή η λεγόμενη ενίσχυση που εξαρτάται από αντισώματα, ADE, είναι από καιρό γνωστή από πειράματα με εμβόλια κορονοιών σε γάτες, για παράδειγμα. Κατά τη διάρκεια αυτών των μελετών, όλες οι γάτες που αρχικά ήταν ανεκτές στο εμβόλιο, μόλις ήρθαν σε επάφή με τον άγριο ιο πέθαναν.(1) (2) (3) (4) (5)

Οι εμβολιασμοί αναμένεται να παράγουν αντισώματα έναντι των ακίδων πρωτεϊνών του SARS-CoV-2. 

Ωστόσο, οι πρωτεΐνες ακίδων περιέχουν επίσης ομόλογες πρωτεΐνες συγκυτίνης, οι οποίες είναι απαραίτητες για το σχηματισμό του πλακούντα σε θηλαστικά όπως οι άνθρωποι. Πρέπει να αποκλειστεί απολύτως ότι ένα εμβόλιο κατά του SARS-CoV-2 θα μπορούσε να προκαλέσει ανοσολογική αντίδραση κατά της συγκυτίνης-1, καθώς διαφορετικά θα μπορούσε να οδηγήσει τις εμβολιασμένες γυναίκες σε στειρότητα αόριστης διάρκειας

Τα εμβόλια mRNA από την BioNTech / Pfizer περιέχουν πολυαιθυλενογλυκόλη (PEG). 

Το 70% των ανθρώπων αναπτύσσουν αντισώματα έναντι αυτής της ουσίας - αυτό σημαίνει ότι πολλοί άνθρωποι μπορούν να αναπτύξουν αλλεργικές, δυνητικά θανατηφόρες αντιδράσεις στον εμβολιασμό.

Η πολύ σύντομη διάρκεια της μελέτης δεν επιτρέπει ρεαλιστική εκτίμηση των μακροχρόνιων αποτελεσμάτων. Όπως και στις περιπτώσεις ναρκοληψίας μετά τον εμβολιασμό της γρίπης των χοίρων, εκατομμύρια υγιείς άνθρωποι θα εκτεθούν σε απαράδεκτο κίνδυνο εάν χορηγηθεί έγκριση έκτακτης ανάγκης και έπειτα θα ακολουθήσει η δυνατότητα παρακολούθησης των μακροχρόνιων επιπτώσεων του εμβολιασμού. Ωστόσο, η BioNTech / Pfizer υπέβαλε αίτηση για έγκριση έκτακτης ανάγκης την 1η Δεκεμβρίου 2020.

ΠΡΟΣΚΛΗΣΗ ΓΙΑ ΒΟΗΘΕΙΑ: Ο Δρ Wodarg και ο Dr. Yeadon ζητούν από όσο το δυνατόν περισσότερους πολίτες της ΕΕ να υπογράψουν την αίτησή τους στέλνοντας το ηλεκτρονικό ταχυδρομείο που προετοιμάστηκε εδώ στον EMA.

Το προσχέδιο του e-mail

Dear Sir or Madam, I am hereby co-signing the petition of Dr. Wodarg and Dr. Yeadon to support their urgent request to stay the Phase III clinical trial(s) of BNT162b (EudraCT Number 2020-002641-42) and other clinical trials. The full text of the petition of Dr. Wodarg and Dr. Yeadon can be found here: 

https://2020news.de/wp-content/uploads/2020/12/Wodarg_Yeadon_EMA_Petition_Pfizer_Trial_FINAL_01DEC2020_EN_unsigned_with_Exhibits.pdf 

I hereby respectfully request that EMA act on the petition of Dr. Wodarg and Dr. Yeadon immediately. 

Regards

Το Ονοματεπώνυμο σας

ΠΡΟΣ

press@ema.europa.eu

ΘΕΜΑ

petitionEMA@corona-ausschuss.com

https://halithheia.blogspot.com/2020/12/wodarg-dr-yeadon.html?m=1&fbclid=IwAR2RGl0JGxR45Hh3OWMLArWE9dap7ZY_x-tAhG1eosskbRWWVUp5EiNzX0Y