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A new study shows the increase in young people's mental health needs started well before the pandemic.
Author: 13newsnow.com
Published: 5:22 PM EDT May 10, 2024
Updated: 5:22 PM EDT May 10, 2024
From spring break parties to Mardi Gras, many people remember the last major normal thing they did before the novel coronavirus pandemic dawned, forcing governments worldwide to issue stay-at-home advisories and shutdowns.
Even before the first case of COVID-19 was detected in the U.S., fears and uncertainties helped spur misinformations rapid spread. In March 2020, schools closed, employers sent staff to work from home, and grocery stores called for physical distancing to keep people safe. But little halted the flow of misleading claims that sent fact-checkers and public health officials into overdrive.
Some people falsely asserted covids symptoms were associated with 5G wireless technology. Faux cures and untested treatments populated social media and political discourse. Amid uncertainty about the viruss origins, some people proclaimed covid didnt exist at all. PolitiFact named downplay and denial about the virus its 2020 Lie of the Year.
Four years later, peoples lives are largely free of the extreme public health measures that restricted them early in the pandemic. But covid misinformation persists, although its now centered mostly on vaccines and vaccine-related conspiracy theories.
PolitiFact has published more than 2,000 fact checks related to covid vaccines alone.
From a misinformation researcher perspective, [there has been] shifting levels of trust, said Tara Kirk Sell, a senior scholar at the Johns Hopkins Center for Health Security. Early on in the pandemic, there was a lot of: This isnt real, fake cures, and then later on, we see more vaccine-focused mis- and disinformation and a more partisan type of disinformation and misinformation.
Here are some of the most persistent covid misinformation narratives we see today:
A loss of trust in the vaccines
Covid vaccines were quickly developed, with U.S. patients receiving the first shots in December 2020, 11 months after the first domestic case was detected.
Experts credit the speedy development with helping to save millions of lives and preventing hospitalizations. Researchers at the University of Southern California and Brown University calculated that vaccines saved 2.4 million lives in 141 countries starting from the vaccines rollout through August 2021 alone. Centers for Disease Control and Prevention data shows there were 1,164 U.S. deaths provisionally attributed to covid the week of March 2, down from nearly 26,000 at the pandemics height in January 2021, as vaccines were just rolling out.
But on social media and in some public officials remarks, misinformation about covid vaccine efficacy and safety is common. U.S. presidential candidate Robert F. Kennedy Jr. has built his 2024 campaign on a movement that seeks to legitimize conspiracy theories about the vaccines. PolitiFact made that its 2023 Lie of the Year.
PolitiFact has seen claims that spike proteins from vaccines are replacing sperm in vaccinated males. (Thats false.) Weve researched the assertion that vaccines can change your DNA. (Thats misleading and ignores evidence). Social media posts poked fun at Kansas City Chiefs tight end Travis Kelce for encouraging people to get vaccinated, asserting that the vaccine actually shuts off recipients hearts. (No, it doesnt.) and some people pointed to an American Red Cross blood donation questionnaire as evidence that shots are unsafe. (PolitiFact rated that False.)
Experts say this misinformation has real-world effects.
A September 2023 survey by KFF found that 57% of Americans say they are very or somewhat confident in covid vaccines. And those who distrust them are more likely to identify as politically conservative: Thirty-six percent of Republicans compared with 84% of Democrats say they are very or somewhat confident in the vaccine.
Immunization rates for routine vaccines for other conditions have also taken a hit. Measles had been eradicated for more than 20 years in the U.S. but there have been recent outbreaks in states including Florida, Maryland, and Ohio. Floridas surgeon general has expressed skepticism about vaccines and rejected guidance from the CDC about how to contain potentially deadly disease spread.
The vaccination rate among kindergartners has declined from 95% in the 2019-20 school year to 93% in 2022-23, according to the CDC. Public health officials have set a 95% vaccination rate target to prevent and reduce the risk of disease outbreaks. The CDC also found exemptions had risen to 3%, the highest rate ever recorded in the U.S.
Unsubstantiated claims that vaccines cause deaths or other illness
PolitiFact has seen repeated and unsubstantiated claims that covid vaccines have caused mass numbers of deaths.
A recent widely shared post claimed 17 million people had died because of the vaccine, despite contrary evidence from multiple studies and institutions such as the World Health Organization and CDC that the vaccines are safe and help to prevent severe illness and death.
Another online post claimed the booster vaccine had eight strains of HIV and would kill 23% of the population. Vaccine manufacturers publish the ingredient lists; they do not include HIV. People living with HIV were among the people given priority access during early vaccine rollout to protect them from severe illness.
Covid vaccines also have been blamed for causing Alzheimers and cancer. Experts have found no evidence the vaccines cause either conditions.
You had this remarkable scientific or medical accomplishment contrasted with this remarkable rejection of that technology by a significant portion of the American public, said Paul Offit, director of the Vaccine Education Center at the Childrens Hospital of Philadelphia.
More than three years after vaccines became available, about 70% of Americans have completed a primary series of covid vaccination, according to CDC figures. About 17% have gotten the most recent bivalent booster.
False claims often pull from and misuse data from the Vaccine Adverse Event Reporting System. The database, run by the CDC and the FDA, allows anybody to report reactions after any vaccine. The reports themselves are unverified, but the database is designed to help researchers find patterns for further investigation.
An October 2023 survey published in November by the Annenberg Public Policy Center at the University of Pennsylvania found 63% of Americans think it is safer to get the COVID-19 vaccine than the COVID-19 disease that was down from 75% in April 2021.
Celebrity deaths falsely attributed to vaccines
Betty White, Bob Saget, Matthew Perry, and DMX are just a few of the many celebrities whose deaths were falsely linked to the vaccine. The anti-vaccine film Died Suddenly tried to give credence to false claims that the vaccine causes people to die shortly after receiving it.
Cline Gounder, editor-at-large for public health at KFF Health News and an infectious disease specialist, said these claims proliferate because of two things: cognitive bias and more insidious motivated reasoning.
Its like saying I had an ice cream cone and then I died the next day; the ice cream must have killed me, she said. And those with preexisting beliefs about the vaccine seek to attach sudden deaths to the vaccine.
Gounder experienced this personally when her husband, the celebrated sports journalist Grant Wahl, died while covering the 2022 World Cup in Qatar. Wahl died of a ruptured aortic aneurysm but anti-vaccine accounts falsely linked his death to a covid vaccine, forcing Gounder to publicly set the record straight.
It is very clear that this is about harming other people, said Gounder, who was a guest at United Facts of America in 2023. And in this case, trying to harm me and my family at a point where we were grieving my husbands loss. What was important in that moment was to really stand up for my husband, his legacy, and to do what I know he would have wanted me to do, which is to speak the truth and to do so very publicly.
Out-of-control claims about government control
False claims that the pandemic was planned by government leaders and those in power abound.
At any given moment, Microsoft Corp. co-founder and philanthropist Bill Gates, World Economic Forum head Klaus Schwab, or Anthony Fauci, former director of the National Institute of Allergy and Infectious Diseases, are blamed for orchestrating pandemic-related threats.In November, Rep. Matt Rosendale, R-Mont., falsely claimed Fauci brought the virus to his state a year before the pandemic. There is no evidence of that. Gates, according to the narratives, is using dangerous vaccines to push a depopulation agenda. Thats false. And Schwab has not said he has an agenda to establish a totalitarian global regime using the coronavirus to depopulate the Earth and reorganize society. Thats part of a conspiracy theory thats come to be called The Great Reset that has been debunked many times.
The United Nations World Health Organization is frequently painted as a global force for evil, too, with detractors saying it is using vaccination to control or harm people. But the WHO has not declared that a new pandemic is happening, as some have claimed. Its current pandemic preparedness treaty is in no way positioned to remove human rights protections or restrict freedoms, as one post said. And the organization has not announced plans to deploy troops to corral people and forcibly vaccinate them. The WHO is, however, working on a new treaty to help countries improve coordination in response to future pandemics.
This story is republished from KFF Health News, a national newsroom that produces in-depth journalism about health issues.
INTRODUCTION
Smallpox eradication was certified in 1980. Mpox has been endemic in Central and West African countries since it was first detected in 1958 (1). It is a zoonosis; cases are often found close to tropical rainforests where various animals carry the orthopoxvirus that causes the disease. In endemic countries, most mpox infections in humans result from a primary animal-to-human transmission. Human-to-human transmission can result from close contact with respiratory secretions, skin lesions of an infected person, or recently contaminated objects. Transmission can also occur via the placenta from mother to fetus or through close contact during and after birth. (2)
As of 21 May 2022, 12 non-endemic countries in two World Health Organization (WHO) regions had reported 92 confirmed cases of mpox. By 26 August 2022, 96 non-endemic countries in all six WHO regions had reported 45 198 confirmed cases of mpox, including 6 deaths. During the same period, endemic countries reported 350 confirmed cases and 6 deaths. In the Region of the Americas,(1) 29 countries and territories reported 23 479 confirmed cases (48%) and 3 deaths (2,3).
Several observational studies on first generation vaccines demonstrated that smallpox vaccination was around 85% effective in preventing mpox (4). At the present time, the original (first-generation) smallpox vaccines are no longer available.
A second-generation smallpox vaccine (ACAM2000) was subsequently developed, which has been used to immunize and protect personnel at high risk of occupational exposure, such as laboratory workers and those whose work in endemic areas (5, 6). A third-generation vaccine based on a modified attenuated vaccinia virus (Ankara strain) was approved for the prevention of mpox in 2019.
Smallpox and mpox vaccines are developed in formulations based on the vaccinia virus, which offer some crossprotection for the immune response to orthopoxviruses. However, the availability of vaccines is limited.
On 31 May 2022, the VIII Ad Hoc Meeting of the Technical Advisory Group (TAG) on Vaccine-Preventable Diseases of the Pan American Health Organization (PAHO) (8) was held to address the outbreak of mpox in several countries. The meetings recommendations were:
On 14 June 2022, the World Health Organization (WHO) published interim guidance on vaccines and vaccination against mpox with the advice and support of its Ad-hoc Working Group on Smallpox and Mpox Vaccines of the Strategic Advisory Group of Experts (SAGE) (9). This interim guidance includes:
On 23 July 2022, the WHO Director-General declared the mpox outbreak a public health emergency of international concern (PHEIC) (10). A coordinated response was launched, aimed at interrupting transmission and protecting vulnerable groups, and a number of recommendations were made, including vaccination.
These temporary recommendations apply to different groups of countries, based on their epidemiological situation, patterns of transmission, and capacities. These recommendations include different aspects such as: the implementation of a coordinated response, community engagement and protection, surveillance and public health measures, clinical management, and infection control, among others. WHO recommends use of the vaccine for countries that have imported cases of mpox in the population and/or human-to-human transmission of monkeypox virus, including in key population groups and communities at high risk of exposure.
The overall goal of the global response to mpox as a PHEIC, is to stop human-to-human transmission and minimize zoonotic transmission of the monkeypox virus wherever it occurs.
The use of vaccines can contribute to this response. However, vaccination should be considered a measure to complement primary public health interventions that include surveillance, early case detection, diagnosis and care, isolation and contact tracing and follow-up, and self-monitoring to reduce contacts.
This document aims to provide useful accessible, and understandable information about mpox vaccines in order to facilitate deployment of vaccination strategies in the context of the current epidemiological scenario and based on the recommendations of the VIII Ad Hoc Meeting of the PAHO Technical Advisory Group (TAG) on Vaccine-Preventable Diseases (8).
This guidance offers a conceptual framework for available vaccines, supporting immunization program managers at the national and subnational levels and vaccinators in technical operations for vaccine utilization.
To facilitate updates, this document is organized around the various components required for deployment and includes relevant information on vaccines, administration techniques, the information system, events supposedly attributable to vaccination or immunization (ESAVI; also known as adverse events following immunization [AEFI]), waste management, and indications for vaccination.
(1) Daily update of the regional epidemiological situation. Pan American Health Organization. Monkeypox cases Region of the Americas. Washington, DC: PAHO. Available from: https://shiny.pahobra.org/monkeypox/
REFERENCES (1) United States Centers for Disease Control and Prevention. About Monkeypox. Atlanta; CDC; 2022. Available from: https://www.cdc.gov/poxvirus/monkeypox/about.html (2) World Health Organization. Mpox (monkeypox). Geneva; WHO; 2022. Available from: https://www.who.int/healthtopics/monkeypox#tab=tab_1 (3) Pan American Health Organization. Weekly Situation Report on Monkeypox Multi-Country Outbreak Response - Region of the Americas. 26 August 2022. Available from: https://www.paho.org/en/documents/weekly-situationreport-monkeypox-multi-country-outbreak-response-region-americas-26 (4) Fine, P; Jezek, B; Grab, B; Dixon, H. The transmission potential of monkeypox virus in human populations. Int J Epidemiol. 1988 Sep;17(3):643-50. Available from: https://academic.oup.com/ije/article-abstract/17/3/643/729853 (5) Food and Drug Administration. ACAM2000 (Smallpox Vaccine) Questions and Answers. Silver Spring: FDA; 2022. Available from: https://www.fda.gov/vaccines-bloodbiologics/vaccines/acam2000-smallpox-vaccine-questions-andanswers (6) Food and Drug Administration. ACAM2000. Silver Spring: FDA; 2019. Available from: https://www.fda.gov/vaccinesblood-biologics/vaccines/acam2000 (8) Pan American Health Organization. VIII Ad Hoc Meeting of PAHOs Technical Advisory Group (TAG) on Vaccine-Preventable Diseases. Technical Briefing on the Multi-Country Monkeypox Outbreak: Recommendations onMonkeypox Vaccines and Vaccination. Washington, D.C.: PAHO; 2022. Available from: https://iris.paho.org/handle/10665.2/56102?locale-attribute=en (9) World Health Organization (WHO). Vaccines and immunization for monkeypox. Interim guidance, June 2022. Geneva: WHO; 2020. Available from: https://apps.who.int/iris/handle/10665/356120?search-result=true&query=Vvccines+and+immunization+for+monkeypox%3A+Interim+guidance%2C+14+June+2022&scope=&rpp=10&sort_by=score&order=desc (10) World Health Organization. WHO Director-Generals statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox - 23 July 2022. Geneva: WHO; 2022. Available from: https://www.who.int/es/director-general/speeches/detail/who-director-general-s-statement-on-the-pressconference-following-IHR-emergency-committee-regarding-the-multi--country-outbreak-of-monkeypox--23-july2022
AstraZeneca has started to pull its Covid-19 vaccine from global markets because of low demand, the pharmaceutical giant said. The decision closes the chapter on a shot that was widely used in the early stages of vaccination drives in many parts of the world before being supplanted by rivals that were better suited to take on an evolving virus.
The move was not related to any concerns about the shots side effects, the company said.
Since the vaccine was approved in Britain in December 2020, over three billion doses have been supplied globally. But in the past few years, demand has plummeted as other manufacturers have released shots tailored to newer variants and countries have opted to use those. AstraZenecas shot, which was developed with Oxford University, is no longer being manufactured or supplied.
The company said it had decided to voluntarily withdraw all licenses to market its Covid vaccine. That process began months ago, and very few active licenses remain, the company said. The Telegraph in Britain earlier reported the decision on Tuesday.
In March, AstraZeneca requested that the vaccine be withdrawn from most European countries. The European Commission approved the move, which went into effect this week.
Sheena Cruickshank, an immunologist at the University of Manchester, said the companys decision to pull the shot was not a surprise. Unlike other manufacturers, AstraZeneca did not update its shot to target emerging virus variants because it used a vaccine technology, known as a viral vector, that was less amenable to such changes.
There was just a recognition that it wasnt going to be a vaccine that could continue to evolve for what we need now, and that it wasnt really useful now because the SARS-CoV-2 virus has changed too much, Dr. Cruickshank said.
In clinical trials, AstraZenecas shot did not perform as well in preventing Covid as Pfizers and Modernas shots did in their own studies, but AstraZenecas still proved highly effective in preventing serious illness and death from the virus.
Concerns about a link between AstraZenecas shot and an extremely rare but serious blood clotting disorder contributed to less demand for the vaccine. Its product information was updated in April 2021 to include risks about the potential side effect. AstraZenecas vaccine was cheaper and easier to transport and store than its competitors. It became the predominant vaccine used in developing countries for much of 2021, when shots from Pfizer and Moderna were mostly going to wealthy nations.
Kim Blomley, an AstraZeneca spokesman, said the company was incredibly proud of the vaccines role in ending the coronavirus pandemic.
The vaccine was distributed in more than 170 countries, and most of its doses were administered in 2021. It was never administered in the United States outside clinical trials.
Amid the safety concerns over AstraZeneca's Covid vaccine Covishield and Vaxzevria, the pharmaceutical giant on Tuesday said it has initiated to withdraw its Vaxzevria vaccine globally, The Telegraph reported. The company, however, said the move is due to a surplus of available updated vaccines since the Covid-19 pandemic, adding that this has led to the decline in demand for the vaccine.
The Telegraph report added that AstraZeneca's application to withdraw the Vaxzervria vaccine was made on March 5 and came into effect on May 7.
Meanwhile, on Tuesday, the company also withdrew marketing authorisation for the vaccine within Europe, reported Reuters.
AstraZeneca's latest move comes days after the Anglo-Swedish drugmaker admitted in a legal document submitted that its Covid vaccines, in very rare cases, can cause Thrombosis Thrombocytopenia Syndrome (TTS) - a rare syndrome characterized by blood clots (thrombosis) and low platelet counts (thrombocytopenia).
However, it also noted that the syndrome can be detected, even if there is no vaccination, adding that expert testimony will be required to determine causation in every case.
Despite this, the company maintained that extensive clinical trial data and real-world evidence consistently support the vaccine's safety and efficacy. It also reaffirmed that the company's first priority is patient safety.
Our sympathy goes out to anyone who has lost loved ones or reported health problems. Patient safety is our highest priority, and regulatory authorities have clear and stringent standards to ensure the safe use of all medicines, including vaccines, a spokesperson for AstraZeneca said in a statement last week.
The pharmaceutical company has been fighting a class action lawsuit against its Covid-19 vaccines, allegedly leading to several deaths across the world. It first began after a man, identified as Jamie Scott, filed a complaint against AstraZeneca, saying that he developed a blood clot and bleed on his brain, which left him with a severe brain impairment after injecting the vaccine.
Additionally, over 50 cases have been filed in the court against AstraZeneca over its vaccine effects.
The Telegraph earlier reported that AstraZeneca has admitted in court papers that its Covid vaccine, Covishield, can cause rare side effect. Covishield was developed by AstraZeneca and was produced by the Serum Institute of India.
The Supreme Court will soon hear a petition on the rare side effects associated with Covishield. While a hearing date has not yet been set, Chief Justice of India DY Chandrachud has acknowledged the petition demanding an expert panel to investigate the vaccine's side effects.
(With inputs from Reuters)
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More than one in nine eligible children nationally did not receive any dose of the measles vaccine in the 2019-21 period and nearly 30% received just one dose. This worrying fact came to light after frequent outbreaks of measles post-Covid prompted researchers from the health ministry's immunization division, Banaras Hindu University and the Bill and Melinda Gates Foundation to take a closer look at vaccination data from the National Family Health Survey (NFHS-5). In some districts in Uttar Pradesh, with high number of births, prevalence of zero-dose children was as high as 34.2% in Prayagraj and 32.2% in Hapur. In almost all northeastern states, zero-dose prevalence was roughly 25%. In a paper published in the journal Vaccine, the researchers investigated dose-wise measles vaccination coverage and explored gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. The study analysed information from 43,864 children taking into account socio-demographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure. The study noted that a significant percentage of children receiving zero doses signalled a concerning gap in immunization coverage. The analysis showed considerable variations between states and districts in zero-dose prevalence. Even within a state, there were significant differences at the district level. For instance, in Arunachal Pradesh, West Siang district had the highest prevalence of children classified as zero-dose cases, 49.6%, while Lower Dibang Valley district had 2.8%. Another major cluster region was in UP where Prayagraj and Banda districts had 34.2% and 32.2% respectively, while in Hapur and Etawah 2.6% and 2.1% were zero-dose children. The analysis found children with higher birth orders and those from the poorest wealth quintile exhibited a higher percentage of zero doses. Mothers with lower levels of education showed increased odds of having zero-dose measles children. Additionally, mothers with limited media exposure demonstrated a higher probability of their children having a zero-dose status for measles. "Measles outbreak is considered an early warning sign for immunization programmes and can be effectively used as a signal for tracing missed and dropout children and overall systems strengthening. It is an ideal tracer as measles outbreaks visibly signal clusters with suboptimal immunization service delivery and can drive prioritisation of targeted interventions to improve programme performance and advocacy," stated the paper. Measles outbreaks were reported in 2022 from several districts of Maharashtra, Bihar, Gujarat, Haryana, Jharkhand, Kerala and Delhi, and measles-related deaths were also recorded subsequently. With humans being the only reservoir for the measles virus and no documented evidence of asymptomatic carriers, it is believed it can be eliminated. In 2017, India adopted the 'National Strategic Plan for Achieving and Sustaining Measles and Rubella Elimination'. In Sept 2022, India adopted a roadmap for eliminating measles and rubella. There is an urgency to reach at least 95% coverage for both doses of measles vaccine as unvaccinated (zero-dose) children "pose an immediate health risk, amplify disease transmission, and act as a barrier to the measles elimination goal". "With consistent efforts, the country aims to catch up on the immunization gaps and vaccinate dropped-out and left-out children this year through Intensified Mission Indradhanush (IMI) 5.0 campaigns. So far six phases of Intensified Mission Indradhanush (IMI) have been conducted from 2017 to 2022 with a focus on measles rubella (MR) elimination vaccinating approximately 1.9 million children," stated the paper.
Patient characteristics and safety
A total of 23 patients with resection-eligible WHO grade III or IV glioma were enrolled and randomized between September 2010 and August 2014. All patients received ATL-DC vaccination as an initial series of 3 biweekly bilateral upper extremity injections of 2.5x10e6 ATL-DCs followed by up to 7 booster injections at 4-month intervals. Randomization allocated nine into the adjuvant TLR-7/8 agonist (resiquimod, 0.2% gel, 3M, applied to ATL-DC injection site days 0, 2, 4 post-DC injection) group, nine into the adjuvant TLR-3 agonist (poly-ICLC, 20mcg/kg IM, Oncovir, upper extremity, at time of DC injection) group, and five to the adjuvant placebo arm where patients received either carrier gel without resiquimod or IM saline injection. (Fig.1A, Supplementary Fig.1). All patients were followed for clinical evaluations, toxicity, survival, imaging changes, as well as in-depth systemic immune monitoring. Baseline patient characteristics are presented and segregated by treatment group in Table1 (see also Supplementary Data1). The median age was 45.3 (range 26.272.8) years, and 57% of the enrolled patients were male. Patients were enrolled prior to the 2016 update to the WHO classification of central nervous system tumors; 65% (n=15) had histopathological diagnoses of WHO Grade IV glioblastoma (now consistent with IDH wild-type glioblastoma), while 35% (n=8) of the patients were WHO Grade III (all of which would now classify as IDH-mutant astrocytoma or oligodendroglioma). Fifty-two percent (n=12) of patients were treated following recurrence, while 48% (n=11) were treated in the newly diagnosed setting. All patients were treated following surgical resection and standard-of-care treatment. The molecular characteristics of the patient tumors are outlined in Table1. Overall, MGMT methylation was seen in 35% (n=8), IDH mutations were observed in 35% (n=8, all grade III), and EGFR amplification was seen in 44% (n=10, all glioblastoma) of patients, consistent with the heterogenous population of malignant glioma patients. There were no statistically significant differences in age, sex, Karnofsky performance status, MGMT methylation status, pre- or postsurgery enhancing tumor volume, nor steroid administration at enrollment. No statistically significant differences were observed between the molecular characteristics, although the number of patients in each treatment group was small.
A Timeline of PBMC acquisition and analysis using CyTOF and/or RNAseq. V = vaccine, D = Day. (Figure created with the help of BioRender). B Schematic of differential gene expression analysis performed on pre-treatment and post-treatment PBMCs of indicated treatment groups. Differentially expressed genes (DEGs) in TLR agonist-treated groups are compared against their changes in the placebo group to identify DEGs specific to the TLR-agonist groups. C, D Enriched gene set terms in Gene Ontology Biological Process (C) or ARCHS4 TF Coexp (D) datasets that significantly overlap with the union of DEGs from ATL-DC + poly-ICLC and ATL-DC + resiquimod groups (P values, FDR-adjusted, two-sided fisher exact test). E Differential gene expression (pre vs. post-treatment fold change, in log2) of representative antigen presentation and IFN-related genes across treatment groups (P values, two-sided Welch t test). F Gene set enrichment score differences (pre vs. post-treatment, delta GSVA score) of representative IFN-related genesets across treatment groups (P values, two-sided Welch t test). G Heatmap of single-sample, gene set enrichment scores (GSVA) of type I and type II interferon genesets in pre-treatment, ATL-DC + placebo, ATL-DC+poly-ICLC and ATL-DC+resiquimod samples. The number of sample pairs analyzed in panels E and F are: ATL-DC+placebo, 5 pairs; ATL-DC+poly-ICLC, 8 pairs; ATL-DC+resiquimod, 8 pairs. The rectangular box in each boxplot represents the interquartile range (IQR), spanning from the first quartile (25th percentile, bottom of box) to the third quartile (75th percentile top of box). Inside the box, the median (50th percentile) is marked. The whiskers (shown as lines extending from the box) extend to the largest and smallest non-outlier values within 1.5 times the IQR, while outliers lie beyond the whiskers.
Overall, the addition of a TLR agonist-induced only Grade 1-2 treatment-related adverse events (TRAEs), and all adverse events reported resolved without further treatment or hospitalization (Table2). The most common TRAEs were rash (39%), fever (35%), and fatigue (26%; see Table2), and were more common in patients treated with resiquimod and poly-ICLC. 88.9% of patients who received resiquimod reported a temporary localized, cutaneous rash that resolved without further treatment. Other observed adverse events were not uncommon in the setting of postoperative central nervous system (CNS) tumor treatment. However, no serious adverse events (Grade 3-4) attributable to the treatment were observed. As such, the addition of a TLR agonist to ATL-DC vaccination in malignant glioma patients was found to be safe and tolerable.
The primary endpoint of this clinical trial was to evaluate systemic immune response changes induced by ATL-DC vaccination with and without TLR agonist administration. As such, we collected PBMCs at baseline (pre-treatment), one day after the vaccination (on treatment), and then following the completion of the treatment cycle (post-treatment) of each patient (Fig.1A). We aimed to understand how the adjuvant administration of TLR agonists modified the immune response in comparison with ATL-DC vaccination alone (placebo control).
We first performed paired bulk RNA-seq on patient-matched, pre-treatment and post-treatment PBMC samples that passed QC (see sample list in Supplementary Data1C). For each gene, we computed the difference between its expression in the pre- and post-samples of patients in each treatment group: ATL-DC+placebo (n=5 pairs); ATL-DC+poly-ICLC (n=8 pairs); ATL-DC+resiquimod (n=8 pairs); for brevity, we refer to them as placebo, poly-ICLC and resiquimod, respectively. To identify expression changes specific to the TLR agonist groups, we identified genes whose average upregulation in the TLR agonist pairs (poly-ICLC or resiquimod) were at least two-fold higher than the placebo pairs (Fig.1B, Supplementary Data2A, see Methods).
Genes upregulated in the TLR agonist groups were involved in antigen processing and were enriched with known interferon-stimulated genes (ISGs) (Fig.1CE, Supplementary Data2B, C). This observation was also confirmed by per-sample gene set enrichment analysis, where the TLR agonist-treated groups displayed higher enrichment of both type I and II interferon downstream gene sets compared to ATL-DC/placebo (Fig.1F, Supplementary Data2D, E). PBMC samples with higher absolute enrichment scores of interferon gene sets were dominated by post-treatment samples from both grade III and IV glioma patients in the TLR-agonist-treated groups (Fig.1G). The two TLR agonist-treated groups showed a largely similar trend in treatment-induced gene expression changes, which included a measurable increase in the expression of ISGs in the peripheral blood of malignant glioma patients. However, we noted that the resiquimod group had a more heterogenous response, which resulted in a lower degree of statistical significance compared to that of the poly-ICLC group.
We performed CyTOF on PBMC timepoints with a 27-marker heavy metal antibody-conjugated panel for 20 of the 23 patients where sufficient material was available (placebo, n=4 pairs; poly-ICLC, n=9 pairs; resiquimod, n=7 pairs; see Supplementary Data1C, 3A, 3B). The panel was selected to be able to broadly characterize different immune cell types, activation/effector, memory, and exhaustion phenotypes, with a bias towards T-cell relevant markers. The different immune cell type populations were visualized by the uniform manifold approximation and projection (UMAP) method (Fig.2A), which we broadly assigned to seven different major immune populations based off the normalized heatmap marker expression (Fig.2B).
A A UMAP projection of the pre- and post-treatment PBMC sample pairs from twenty patients (placebo, n=4 pairs; poly-ICLC, n=9 pairs; resiquimod, n=7 pairs). Clustering was performed with a random sampling of 5,000 cells from each patient. B Heatmap of normalized expression of all 27 cell markers within cell populations identified in the patient PBMCs. C, D Normalized expression of indicated markers in monocyte (C), or T cell populations (D) within the PBMC samples of patients from indicated treatment groups. P values, two-sided Wilcoxon rank sum test. E, UMAP projection of the PBMC-derived single cells (n=99,590). The immune subset associated with each cluster is inferred based on the clusters differentially expressed transcripts. Canonical markers of known immune subsets are shown. F, G Heatmaps showing the union of recurrent DEGs computed between ATL-DC treated samples (combined with placebo, resiquimod or poly-ICLC) and pre-treatment samples in the myeloid populations (F) or lymphocyte populations (G). Shown in the heatmaps are the log fold change values of the DEGs in each cell population grouped by their treatment groups. The number of sample pairs analyzed in C and D are: ATL-DC+placebo, 4 pairs; ATL-DC+poly-ICLC, 9 pairs; ATL-DC+resiquimod, 7 pairs. The rectangular box in each boxplot represents the interquartile range (IQR), spanning from the first quartile (25th percentile, bottom of box) to the third quartile (75th percentile the top of box). Inside the box, the median (50th percentile) is marked. The whiskers (shown as lines extending from the box) extend to the largest and smallest non-outlier values within 1.5 times the IQR, while outliers lie beyond the whiskers.
After 3 cycles of treatment, the post-treatment samples of patients in the TLR agonist groups showed a significant increase in the proportion of proliferating Ki67+CD14+ classical monocytes (Fig.2C, Supplementary Data3C). Such findings were corroborated by the increased monocyte fraction and CD14 transcript expression after ATL-DC+TLR agonist-treated samples (Supplementary Fig.2A, B, Supplementary Data3D). ATL-DC+TLR agonist treatment induced PD-1 expression in CD4 T cell population and increased the T-cell normalized expression of PDCD1 (the transcript that encodes PD-1 protein) and TCF7 (a marker of progenitor-like T cells) (Fig.2D, Supplementary Fig.2C). Moreover, expression of markers associated with irreversible T cell exhaustion, such as CD38 and CD3933,34, were also significantly reduced after ATL-DC+TLR agonist treatment (Fig.2D, Supplementary Fig.2D). Increased expression of PD-1 and decreased expression of CD38 and CD39 suggest the addition of the TLR agonists led to enhanced systemic T cell activity and cellular fitness in the patient.
To delineate the changes induced by ATL-DC and TLR agonist treatment in discrete peripheral blood immune cell subsets, we performed single-cell RNA-seq on selected patients at baseline and then following the completion of therapy. We analyzed two representative sample pairs from each cohort (placebo, poly-ICLC, and resiquimod) (Supplementary Data1C, 3E). We identified a total of twelve clusters from the total PBMC immune cell population and annotated these clusters based on differentially expressed gene markers in each cluster. From the initial clustering, we were able to identify multiple populations of CD4+ and CD8+ T cells, two populations of NK cells, three monocytic cell populations, B cell, and dendritic cells (type 2 conventional dendritic cells (cDC2) and plasmacytoid dendritic cells (pDCs), in accordance with the previous characterization of these cell types in peripheral blood (Fig.2E and Supplementary Fig.2E, F).
Differential gene expression analysis across the different lymphoid and myeloid populations revealed concordant upregulation of known ISGs (e.g. IFI6/35/44L, ISG15/20, IFIT3, IFITM1/3, GBP1/5, MX1, STAT1, and CXCL10) and antigen presentation-related proteasomes (PSMB9 and PSME2) in both TLR agonist sample pairs. The magnitude of induction was weaker in the paired PBMC samples obtained from the resiquimod group compared to the poly-ICLC group (Fig.2F, G).
Thus, our combination of high dimensional proteomics, bulk and single-cell RNAseq demonstrates how adjuvant TLR administration in conjunction with ATL-DC reproducibly increases the proportion of canonical CD14+ monocytes within the systemic blood circulation. This TLR agonist administration was also associated with enhanced T cell activity, coupled with decreased expression of CD38 and CD39 and their downstream T cell-suppressive adenosine pathway33,34,35. ATL-DC+TLR agonist-driven induction of ISGs across lymphoid and myeloid populations identified in our scRNAseq analysis corroborated our bulk transcriptomic analysis. Given the consistent changes observed with TLR agonist administration, we examined whether these systemic measurements correlated the observed progression-free and overall-survival differences between these patient populations to speculate on their contribution.
Median follow-up of patients treated on this clinical trial was 2.2 years after surgery, although the long-term survivors have now been followed for over 10 years. Median progression-free survival (PFS) was 8.1 months; and median overall survival (OS) was 26.6 months. Although this clinical trial was not designed or powered to detect effects of these treatments on survival between the treatment groups, there were noticeable differences in median survival between the treatments groups for both OS (placebo: 7.7 months, poly-ICLC: 52.5 months, and resiquimod: 16.7 months; log-rank P=0.017) and PFS (placebo: 5.5 months, poly-ICLC: 31.4 months and resiquimod: 8.1 months; log-rank P=0.0012) (Fig.3A). Because the trial included patients with both grade III and IV tumors, we stratified our analysis based on tumor grade. When we analyzed only the grade IV (GBM) patients, we observed a trend towards improved PFS (log-rank P=0.068) and OS (P not significant) (Fig.3B). Interestingly, for the IDH mutant/Grade III cohort, all four patients that received ATL-DC + poly-ICLC treatment are still alive at the data cutoff date (three of the patients have survival > 120 months and one > 112 months), and they have significantly longer OS and PFS compared to the other (n=4) grade III patients who received ATL-DC + resiquimod or ATL-DC alone where median OS was 15.73 months (Fig.3C).
AC Progression-free survival (PFS, top) and overall survival (OS, bottom) of all patients (A), patient subset with GBM (B), or grade III glioma (C) in indicated treatment groups. P values, log-rank test. D, E, Multivariate Cox proportional hazards analysis assessing the hazard ratios of tumor progression in TLR agonist treatment groups against placebo in all patients (D) or GBM subset (E) after adjusting for other clinical covariates (Tx_Group=treatment group, RecurNum=number of recurrences prior to ATL-DC treatment). In the forest plot, the squares are the hazard ratio (HR) estimates, the error bars are 95% confidence interval (CI) of the HR, the P value of each covariate is based on its Wald statistics, the P values are not adjusted. In D, the sample distribution in each covariate is Tx_Group: placebo=5, poly-ICLC=9, resiquimod=9; Grade: III=8, IV=15; MGMT_methylation: True=8, False=15. In E, Tx_Group: placebo=4, poly-ICLC=5, resiquimod=6. F, MR-computed volumes of post-treatment, recurrent tumors in indicated treatment groups. Treatment groups: Placebo (n=5), Resiquimod (n=8); Poly ICLC (n=9). P values, unpaired, two-sided Wilcoxon rank sum test.
We performed multivariate Cox proportional hazard (PH) analysis, adjusting for clinical variables that are significantly correlated with OS or PFS as a single variable (tumor grade, MGMT methylation status, and number of recurrences). Our analysis confirmed that patients in the poly-ICLC and resiquimod treatment groups had a lower risk of progression that was independent of grade, MGMT methylation, and number of recurrences (Fig.3D). Risk of death was significantly lower in the poly-ICLC group, while the resiquimod group showed a similar trend that was not statistically significant (Supplementary Fig.3A). In the GBM patient subset, TLR agonist treatment also significantly lowered risk of recurrence, but not risk of death (Fig.3E, Supplementary Fig.3B).
To determine whether this treatment directly impacted tumor volume, MR imaging was performed, and contrast-enhancing tumor volume was quantified over time. We noted that the rate of tumor volume increase over time in the ATL-DC/placebo treatment cohort was higher than in the ATL-DC/resiquimod treatment (p=0.022) and the ATL-DC/poly-ICLC treatment groups (P<0.001; Fig.3F). Anecdotally, we observed an increased T2/FLAIR MRI signal after completion of the vaccine series in two of the four long-term survivors who received ATL-DC/poly-ICLC (Supplementary Fig.3C, D), although such findings are potentially confounded by prior radiation therapy, and thus we cannot ascribe such changes solely to the vaccine/TLR agonist intervention. However, this increased post-vaccination T2/FLAIR on MRI was not seen in patients who did not receive poly-ICLC (not shown).
Finally, we asked if the magnitude of interferon pathway induction by the adjuvant TLR agonist treatment directly correlated with OS or PFS. This could allow for the use of an interferon activity score as a biomarker for productive anti-tumor immune responses following ATL-DC immunotherapy. To this end, we stratified the patients by the median GSVA score of the HALLMARK INTERFERON GAMMA RESPONSE gene set in post-treatment PBMC samples. We confirmed that patients whose post-treatment samples displayed higher interferon gene set scores (median) had longer OS and PFS than those with lower scores (Fig.4A, Supplementary Fig.4A). Separate analyses on the grade IV (GBM) and grade III glioma patients showed a concordant trend but with a lower degree of statistical significance; this was likely caused by the small sample sizes. Notably, multivariate Cox PH analysis strongly suggested that the interferon gene set score is a significant predictor of tumor recurrence (Fig.4B, C) and death (Supplementary Fig.4B), even after adjusting for other potentially confounding clinical variables. To ensure that the correlation is not specific to this single gene set, we confirmed that the gene set scores of other interferon gene sets after ATL-DC treatment are also positively correlated with the patients OS and PFS (Supplementary Data4A, B). Such findings can be confirmed in larger subsequent studies.
A Kaplan-Meier progression-free survival curves of all patients (left), GBM (center), and Grade III glioma subsets (right) stratified by their HALLMARK_INTERFERON_GAMMA_RESPONSE GSVA scores in their post-treatment PBMCs. P values, log-rank test. B, C Multivariate Cox proportional hazards analysis assessing hazard ratios of tumor progression in patients with high HALLMARK_INTERFERON_GAMMA_RESPONSE GSVA score in all patients (B) or GBM subset (C) after adjusting for other clinical covariates. In the forest plot, the squares are the hazard ratio (HR) estimates, the error bars are 95% confidence interval (CI) of the HR, the P value of each covariate is based on its Wald statistics, the P values are not adjusted. In B, the sample distribution in each covariate is GSVA score (post-Tx): Taken together, these data suggest that the addition of TLR agonists to ATL-DC vaccination shifts towards an interferon-induced immune response in both lymphoid and myeloid cells. Poly-ICLC and resiquimod appear to upregulate similar ISGs but with different magnitude. Enhancing systemic ISG-signaling may reflect an environment more favorable towards the generation of an antitumor immune response and clinical effects.
By Emily Stearn, Health Reporter For Mailonline 11:39 08 May 2024, updated 14:58 08 May 2024
AstraZeneca's Covid vaccine once heralded as a 'triumph for science' is being withdrawn worldwide.
The jab, developed withOxford University, can no longer be used in the European Union after the company voluntarily pulled its 'marketing authorisation', coming into effect today.
Similar applications to withdraw the vaccine will be made in other countries which had previously approved it, including the UK. Around 50million doses were given in Britain.
While creditedwith saving more than 6million lives, the jab known as Vaxzevria has come under intense scrutiny in recent months over a rare but fatal side effect.
In February, thepharmaceutical titanadmitted in documents lodged with the High Court that it 'can, in very rare cases, cause thrombocytopenia syndrome (TTS)'.
So why has the jab now been withdrawn? Are you at risk if you had Vaxzevria? And what do you have to prove if you have been injured by the AstraZeneca vaccine?
Here, MailOnline explains everything you need to know.
Why has it been withdrawn?
Fifty-one families are currently pursuing legal action against AstraZeneca, arguing its 'defective' jab was to blame for their injuries and deaths of loved ones.
However, the Cambridge-based drug manufacturer denies the decision to withdraw the vaccine is related to the court case. Instead, it insists Vaxzevria is being removed from markets for commercial reasons.
The company said in court documents that the vaccine is reportedly no longer being manufactured or supplied, having been superseded by updated vaccines that tackle newer variants.
In a statement today, the company said:'According to independent estimates, over 6.5million lives were saved in the first year of use alone and over three billion doses were supplied globally.
January 2020: Oxford University scientists start working on a Covid vaccine after the World Health Organization declares the spread of the virus a 'Public Health Emergency of International Concern'
March 2020: Then Prime Minister Boris announced the first national lockdown. That same month, the Government invests 88million in the development of the Oxford vaccine
April 2020: Alongside AstraZeneca, scientists start the first clinical trials of their new vaccine. This involved 1,000 volunteers in the UK
July 2020: Results from phase two trials of AstraZeneca's jab are published
4 December 2020:Covid jab rollout begins with the Pfizer vaccine. Over-80s and care home workers are given priority
8 December 2020:Phase three trial results of theAstraZeneca's jab are published. These are what health officials will use to approve the jab for use in the UK
30 December 2020:AstraZeneca's jab is approved for emergency use
4 January 2021: FirstAstraZeneca doses start being dished out.Brian Pinker, 82, is the first person to receive the jab outside of clinical trials
8 January 2021: Frontline NHS staff start being offered vaccines
8 February 2021: Over-70s are called forward
14 February 2021: Roll-out opens up to Brits with underlying heath conditions, as well as the over-65s
28 February 2021: All over-60s are invited for jabs
11March 2021:European countries start suspending use of the AstraZeneca jab after death of a 60-year-old woman from a blood clot
17 March 2021: Over 50s start being offered Covid jabs in the UK
19 March 2021: Several European countriesreverse decision to suspendAstraZeneca jab after initialinvestigations find no link to reported blood clots
31 March 2021: People living with vulnerable adults are called forward to get a Covid vaccine in the UK, even if they are younger than eligible age groups
7 April 2021:UK restricts the use of the AstraZeneca vaccine to over-30s over a small but statistically significant risk of blood clots in younger people
30 April 2021: Over-40s are called forward for Covid jabs
7 May 2021: Restriction of the AstraZeneca vaccine is widened to include over-40s
August 2022: Government sources say they will not order anymore AstraZeneca Covid vaccines instead focuses on mRNA alternatives
March 2023: Dozens of patients and families launch legal action against AstraZeneca due to
April 2023: Widower of a BBC presenter Lisa Shaw who died after having the vaccine said he has 'no alternative' but to sue AstraZeneca
4 August 2023: Anish Tailor, whose wife Alpa died in March 2021 after receiving her first AstraZeneca dose, filed a product liability claim against AstraZeneca at London's High Court.His lawyer says he has nearly 50 other clients who will formally sue AstraZeneca in the coming months
17 August 2023: IT engineer Jamie Scott, who suffered a brain haemorrhage the day after his first AstraZeneca jab starts a legal case against the company. The law firm representing Mr Scott says it represents around 40 other individuals or bereaved families
'Our efforts have been recognised by governments around the world and are widely regarded as being a critical component of ending the global pandemic.
'As multiple, variant Covidvaccines have since been developed, there is a surplus of available updated vaccines.
'This has led to a decline in demand for Vaxzevria, which is no longer being manufactured or supplied.
'AstraZeneca has therefore taken the decision to initiate withdrawal of the marketing authorisations for Vaxzevria within Europe.'
What did the original trial data show about side effects?
Tens of thousands of volunteers, including ones in the UK and the US, willingly rolled up their sleeves to take part in original trials.
Heavily scrutinised data suggested two doses of the AstraZeneca jab offered about 70 per cent protection against becoming ill. This meant developing any symptoms, as opposed to being hospitalised.
Other studies calculated that a single dose reduced the likelihood of hospitalisation by up to 94 per cent.
Analysis of the phase 3 trial, the final hurdle typically needed to be cleared before any drug gets approved for widespread human use, noted no safety concerns.
Yet, like with all forms of medication, AstraZeneca's jab carried a range of potential side effects.
Officials knew about mild ones thanks to the massive trials, with recipients mostly complaining of routine issues like headaches.
And people who were subsequently vaccinated were warned about them ahead of getting any needle in their arm.
Common side effects, which health bosses say can affect more than 10 per cent of recipients, include fatigue, 'flu-like'symptoms, and pain in the arms or legs.
Stomach pain, a rash and excessive sweating were uncommon, strikes roughly one in 100 people who get vaccinated.
According to the pharmaceutical titan, rare (approximately one in 1,000) issues included facial drooping on one side.
It was only once the door was opened for millions more Brits to get the jab, as the UK did during the first few months of 2021, that another complication was spotted.
Officials noted a small, yet significant trend in cases of vaccine-induced immune thrombotic thrombocytopenia (VITT, or TTS)that allowed them to raise the alarm in the first week of April.
It causes blood clots to form in various parts of the body, including the brain, heart, lungs, kidneys, and the legs. It is an urgent medical emergency.
These blood clots, like any others, can be deadly depending on where they form or if they break up and travel to parts of the body like the brain.
Estimates suggest the risk of blood clots occurring from taking AstraZeneca's jab is in the region of one in 50,000.
Am I at risk now if I had the jab back in 2021?
Side effects from the AstraZeneca vaccine generally only occurred within the first four weeks of receiving it.
There is currently no evidence of a long-term risk from having had the jab, doctors insist.
As jabs are given as a single dose at a time, experts claim adverse effects generally only occur a short time after receiving the injection unlike with medication that people take for years.
Additionally, given the sheer quantity of people who received the AstraZeneca jab, some 50million in the UK and over 2.5billion globally, long-term effects would likely have been spotted by now, experts say.
How do you prove you have been injured by Vaxzevria?
The Vaccine Damage Payment Scheme,which has been around since the 70s, offers people, or their families, a tax-free sum of 120,000.
Established back in 1979, the policy covers covers an array of vaccines recommended by the Government, including measles, mumps and rubella and is meant to reassure people that, in the unlikely event something goes wrong, the state will provide support.
Under current rules however,strict eligibility criteria means those affected must either have been killed or be left 60 per cent disabled due to a vaccine.
This means a person theoretically judged to be only 59 per cent disabled will not get a penny.
The extent of a person's disability is based on an assessment by a doctor and can include both physicaldisablement, such as the loss of a limb, or mentaldisablement, such as a decline cognitive function.
It also means there is no escalation of the sum received.
So, for example, someone who is completely paralysed by a vaccine would receive the same 120,000 as someone who lost a leg.
Going blind or deaf counts as being 100 per cent disabled.
Brits can only make a claim for a child once they are two years old.Adults must apply within six years of having a vaccine.
What is the three year cut-off for compensation claims?
Government officials caution it can take at least six months to process a Vaccine Damage Payment claim. Covid vaccine specific claims 'will take longer'.
Under theConsumer Protection Act 1987, Brits also have a right to sue vaccine producers if a jabdefect has caused personal injury.
Lawyers representing 51 victims and families are currently undertaking such action against AstraZeneca,arguing the vaccine was 'a defective product' that was 'not as safe as consumers generally were reasonably entitled to expect'.
The pharmaceutical titan has strongly denied these claims.
You may have had a combined vaccination against a number of the diseases listed. For example, you might have been vaccinated against DTP (diphtheria, tetanus and pertussis) or MMR (measles, mumps and rubella).
You may also be able to get a payment if you're severely disabled because either:
Source: Gov.uk
Those injured or bereaved, however only have three yearsfrom the date of their injury or death in which to bring a claim.
Last month,Sarah Moore, a partner at law firm Leigh Day, who is representing alleged victims, told MailOnline the true toll of people injured may never be uncovered.
'The criteria for what constituted VITT was really only published and made available to the clinical community from the beginning of March (2021),' she said.
'We may never know if there were other injuries that could have been related to the vaccine before March 2021.
For the claims we are bringing, those injured or bereaved have three years from the date of their injury or the death in which to bring a claim so unfortunately in many cases that cut off has now been reached.'
How many Brits have been injured by the jab?
TTS is thought to be linked to at least 81 deaths in the UK, according to figures collated by UK drug watchdog, the MHRA.
Not all are proven, however. And not every family is seeking legal action.
No figures are provided for the number of people left disabled from AstraZeneca's Covid jab.
According to figures released by NHS Business Services Authority (NHSBSA) under freedom of information laws, the payment scheme has received more than 11,000 Covid vaccine claims as of April 2.
Of these, 168 claims for state-funded financial support have now been approved.
Fewer thanfive were Pfizer and Moderna, withthe remaining claims all AstraZeneca.
The successful claims cover those affected by VITT.
Others developedGuillain-Barre syndrome, anaphylaxis or suffered other blood clots.
More than 4,800 claims have been rejected, including 324 who were unsuccessful because they failed to meet the 60 per cent threshold.
'Althoughthe claims met the criteria for causation, the independent medical assessor recommended that the vaccine has not caused severe disablement,' the NHSBSA said.
When were officials first aware of the risk?
Health officials first identified cases of VITT linked to AstraZeneca's jab in Europe as early as March 2021, just over two months after the vaccine was first deployed in the UK.
However, it wasn't until April that year that evidence became clear enough that the jab started to be restricted.
Spooked officials first restricted the jab to only people over 30. They then narrowed this to only over-40s in May 2021.
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European countries have reported a surge in whooping coughc ases in first quarter of 2024, with 10 times as many identified as in each of the previous two years.
Nearly 60,000 cases were reported by European Union and European Economic Area countries over the period, the European Centre for Disease Prevention and Control said on Wednesday, with 11 deaths in infants and eight among older adults.
In the UK cases of whooping cough could reach a 40-year high in 2024, experts have warned amid a rapid rise in cases.
Whooping cough, or pertussis, is a bacterial infection of the lungs and airways, and is endemic in Europe. It can be very dangerous for young babies or older people.
Bigger whooping cough epidemics are expected every 3-5 years even in countries with high vaccination rates, the ECDC said, although a slight dip in immunisation during the COVID-19 pandemic may have been a factor in the rise. Circulation of whooping cough was also very low during the pandemic and its related restrictions on movement, making the rise seem larger.
After about a week, you or your child:
The cough may last for several weeks or months.
The numbers are still historically high, though. In the first three months of 2024, there have already been as many cases as there were in an average year between 2012 and 2019.
The agency noted that much of the population had missed out on natural boosting of their immunity to whooping cough because they had not been exposed to it during the pandemic.
Babies under six months are at particular risk from the infection.
Its essential to remember the lives at stake, especially our little ones. Vaccines against pertussis have proven to be safe and effective, said ECDC Director Andrea Ammon.
Most European countries routinely immunise children against pertussis and many also vaccinate pregnant women to protect their babies.
The ECDC said some countries may want to consider giving boosters to older children and adults too, as immunity can wane.
Paul Hunter, professor in medicine at the University of East Anglia (UEA), said: For most adults the whooping cough is not life threatening, though can be very unpleasant.
This is a chronic repeated bout of coughing which can be so bad that people feel it a struggle to breathe in again.
It used to be much more common in the last century up until the vaccine was introduced.
However, this current year looks like we may see more cases than we have seen in any of the last 40 years.
Prof Hunter said that a number of factors could be behind the rise in cases, including: a drop in vaccine uptake; reduced population immunity due to a fall in cases linked to social distancing measures during the pandemic; and a scare over vaccines in the early 2000s which led to a group of people aged around 21 who did not complete their vaccination.
He added: The infection can affect anyone who is not vaccinated and even some that are.
However, the main risk of death or severe long-term complications is seen in young children, especially those under three months old.
It is this age group that are most at risk of death and developing longer-term problems such as brain damage.
The problem is that this age group is too young for the vaccine in most circumstances.
That is why we offer vaccine to pregnant women. Not to protect them but to protect their babies during the riskiest first months of life.
Vaccine uptake in pregnant women has been falling quite markedly in recent years.
