Rare but deadly blood clots tied to Johnson & Johnson and AstraZeneca Plcs Covid-19 shots were caused by an autoimmune reaction that some people are predisposed to, researchers found, a discovery that they say will shape development of future vaccines.
Adenovirus-based vaccines, like the J&J and AstraZeneca shots that were later pulled from the market, contain a component that, in genetically susceptible people, can trigger the production of unusually structured antibodies against a protein involved in blood clotting, scientists said Wednesday in a letter to the New England Journal of Medicine. Researchers plan to identify the culprit and then try to remove it using genetic engineering.
Read More: How COVID-19 Vaccines and Infections Are Tweaking Our Immunity
An extremely similar deleterious antibody response occurs in susceptible patients after infection with adenoviruses, which often infect the airways and lead to cold-like symptoms, the study found. Its not known how many people may be susceptible to the complication, said Tom Gordon, head of immunology at Flinders University in South Australia, whose molecular sleuthing led to the finding.
The immune reaction linked to the shot is a new disease, he said in an interview. Hematologists and intensive care specialists are likely to spot more cases as they become familiar with it, he said.
Its a kind of autoimmunity where we know the trigger, said immunologist James McCluskey, assistant vice chancellor of the University of Melbourne, who wasnt involved in the research. Thats unusual. In most cases we never get a handle on the trigger.
Out of more than 18 million people who received the single-dose J&J vaccine,60 casesof the clotting disorder were reported and nine people died, according to the Yale School of Medicine.
A small number of clot-related deaths tied to the AstraZeneca vaccine led to its withdrawal or restriction in Denmark, Norway and other countries in 2021. The complication occurred in about 2-3 people per 100,000 vaccinated with the Astra shot under age 60 in Australia, where it hasnt been available since March 2023. The European Commission withdrew the marketing authorization for the immunization in March 2024.
AstraZeneca welcomes any further examination of the possible underlying mechanism of thrombosis with thrombocytopenia syndrome (TTS), given that, despite extensive investigation, we do not yet understand the mechanism that can in very rare cases be a trigger for TTS, a spokesperson for the company said.
J&J also said it supports research that helps guide development of safe and effective vaccines.
Read More: The Miracle Workers: Vaccine Scientists Are TIMEs 2021 Heroes of the Year
More data are needed to fully understand potential factors that may be associated with this rare event, including its potential relationship with adeno- and other viruses, to draw appropriate conclusions about the underlying pathogenesis, the company said in an email.
Both shots played an important role in vaccine programs during the early stages of the pandemic. One analysis found the Astra vaccine saved an estimated 6.3 million lives in 2021.
The mRNA vaccines made by the Pfizer Inc.-BioNTech SE partnership and Moderna Inc. were later found to be more effective at protecting against Covid and have been updated to tackle more recent virus variants.
image:
Flinders University immunology researchers Dr Jing Jing Wang and Professor Tom Gordon.
Credit: photo courtesy Flinders Foundation
New research led by Flinders University and international experts is expanding understanding of vaccine-induced immune thrombocytopenia and thrombosis (known as VITT).
At the height of the COVID-19 pandemic in 2021,VITT emerged as a new disease following adenovirus vector-based vaccines notably the Oxford-AstraZeneca vaccine.
VITT was found to be caused by an unusually dangerous blood autoantibody directed against a protein termed platelet factor 4 (or PF4).
In separate research in 2023, researchers from Canada, North America, Germany and Italy described a virtually identical disorder with the same PF4 antibody that was fatal in some cases after natural adenovirus (common cold) infection.
Flinders University researchers Dr Jing Jing Wang and Flinders Professor Tom Gordon, Head of Immunology at SA Pathology in South Australia,led a previous studyin 2022 which cracked the molecular code of the PF4 antibody and identified a genetic risk factor related to an antibody gene termed IGLV3.21*02.
Now, the Flinders group has collaborated with this international group of researchers to find that the PF4 antibodies in both adenovirus infection-associated VITT and classic adenoviral vectored VITT share identical molecular fingerprints or signatures.
The research will also have implications for improving vaccine development, says Flinders University researcher Dr Wang, first author on the new article to be published in the eminentNew England Journal of Medicineon Thursday (embargoed 16 May 2024).
These findings, using a completely new approach for targeting blood antibodies developed at Flinders University, indicate a common triggering factor on virus and vaccine structures that initiates the pathological pF4 antibodies, explains Professor Gordon.
"Indeed, the pathways of lethal antibody production in these disorders must be virtually identical and have similar genetic risk factors.
"Our findings have the important clinical implication that lessons learned from VITT are applicable to rare cases of blood clotting after adenovirus (a common cold) infections, as well as having implications for vaccine development," he says.
Key points:
The original research letter, Correspondence entitled 'Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders' (2024), by Jing Jing Wang (Flinders University), Linda Schnborn (Greifswald University Hospital, Germany), Theodore E Warkentin (McMaster University, Canada), Tim Chataway (Flinders University), Leonie Grosse (Ludwig Maximilians University, Germany), Paolo Simioni (Padova University Hospital, Italy), Stephan Moll (University of North Carolina School of Medicine, US), Andreas Greinacher (Greifswald University Hospital, Germany) and Tom P Gordon (SA Pathology, South Australia) will be published in theNew England Journal of Medicine.DOI: 10.1056/NEJMc2402592
Disclaimer:The views expressed in this letter are those of the authors and do not necessarily represent the position of the European Medicines Agency.
Acknowledgements: The research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) and a European Medicines Agency service contract. Dr Schnborn was supported by theASH Global Research Award from the American Society of Hematology and by the Gerhard Domagk Research Program through the Medical University of Greifswald. Dr Wang was supported by a Flinders Foundation Health Seed Grant.
New England Journal of Medicine
Observational study
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Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders
16-May-2024
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Australian researchers have uncovered a link between an "unusually dangerous" COVID-19 vaccine complication and rare but potentially fatal blood disease contracted by some people who caught a cold.
The antibodies from the two conditions vaccine-induced immune thrombocytopenia and thrombosis (VITT), and an adenovirus VITT-like disorder share almost identical molecular signatures or fingerprints, Adelaide's Flinders University announced today.
"These findings, using a completely new approach for targeting blood antibodies developed at Flinders University, indicate a common triggering factor on virus and vaccine structures that initiates the pathological PF4 antibodies," the university's Professor Tom Gordon said.
READ MORE: mRNA cancer vaccine shows 'promising' results, US study finds
"Indeed, the pathways of lethal antibody production in these disorders must be virtually identical and have similar genetic risk factors."
The research comes after VITT emerged as a complication that occurred in some rare cases after receiving some COVID-19 vaccines, including the Oxford-AstraZeneca jab used in Australia.
"VITT was found to be caused by an unusually dangerous blood autoantibody directed against a protein termed platelet factor 4 (or PF4)," Flinders University said in a statement.
READ MORE: Why the budget's predicting lower inflation but same old interest rates
Separately to research into the vaccine side-effect, experts from North America and Europe last year found an almost-identical blood disease with the same PF4 antibody that was fatal for some people who had recently had a common cold.
Flinders researchers Gordon and Dr Jing Jing Wang led a study in 2022 that "cracked the molecular code of the PF4 antibody and identified a genetic risk factor", the university said.
The latest COVID-19 strain spreading across the world
The groups from Flinders University and overseas collaborated to find the matching molecular fingerprints, publishing their findings in the New England Journal of Medicine today.
Both Gordon and Wang said the findings would play an important role in improving vaccine safety.
"Our findings have the important clinical implication that lessons learned from VITT are applicable to rare cases of blood clotting after adenovirus (a common cold) infections, as well as having implications for vaccine development," Gordon said.
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Children aged 6 months4 years should get two or three doses of updated COVID-19 vaccine depending on which vaccine they receive.
Children aged 6 months4 years who got COVID-19 vaccines before September 12, 2023, should get one or two doses of updated COVID-19 vaccine depending on which vaccine and the number of doses theyve previously received.
People ages 65 years and older should receive 1 additional dose of any updated (20232024 formula) COVID-19 vaccine (i.e., Pfizer-BioNTech, Moderna, or Novavax) at least 4 months following the previous dose of updated (20232024 Formula) COVID-19 vaccine.
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People aged 65 and older who have not previously received any COVID-19 vaccine doses and choose to get Novavax should get 2 doses of updated Novavax vaccine, followed by 1 additional dose of any updated 20232024 COVID-19 vaccine to be up to date.
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COVID-19 vaccines currently recommended for use in the United States:
As of October 3, 2023, the 2023-2024 updated Novavax vaccine was recommended by CDC for use in the United States.
As of September 12, 2023,the20232024 updated Pfizer-BioNTech and Moderna COVID-19 vaccines were recommended by CDC for use in the United States.
The 20232024 updated COVID-19 vaccines more closely targets the XBB lineage of the Omicron variantand could restore protection against severe COVID-19 that may have decreased over time. We anticipate the updated vaccines will be better at fighting currently circulating variants.
There is no preferential recommendation for the use of any one COVID-19 vaccine over another when more than one licensed or authorized, recommended, and age-appropriate vaccine is available.
If you recently had COVID-19, you still need to stay up to date with your vaccines, but you may consider delaying your vaccine by 3 months.
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Lead, Vaccine Effectiveness and Policy Team, Coronavirus and Other Respiratory Virus Division, Centers for Disease Control and Prevention, Atlanta, Georgia
Disclosure: Katherine E. Fleming-Dutra, MD, has disclosed no relevant financial relationships.
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New research led by Flinders University and international experts is expanding understanding of vaccine-induced immune thrombocytopenia and thrombosis (known as VITT).
At the height of the COVID-19 pandemic in 2021, VITT emerged as a new disease following adenovirus vector-based vaccinesnotably the Oxford-AstraZeneca vaccine.
VITT was found to be caused by an unusually dangerous blood autoantibody directed against a protein termed platelet factor 4 (or PF4).
In separate research in 2023, researchers from Canada, North America, Germany and Italy described a virtually identical disorder with the same PF4 antibody that was fatal in some cases after natural adenovirus (common cold) infection.
Flinders University researchers Dr. Jing Jing Wang and Flinders Professor Tom Gordon, Head of Immunology at SA Pathology in South Australia, led a previous study in 2022 which cracked the molecular code of the PF4 antibody and identified a genetic risk factor related to an antibody gene termed IGLV3.21*02.
Now, the Flinders group has collaborated with this international group of researchers to find that the PF4 antibodies in both adenovirus infection-associated VITT and classic adenoviral vectored VITT share identical molecular fingerprints or signatures.
The research will also have implications for improving vaccine development, says Flinders University researcher Dr. Wang, first author on the article published in the New England Journal of Medicine and titled "Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders."
"These findings, using a completely new approach for targeting blood antibodies developed at Flinders University, indicate a common triggering factor on virus and vaccine structures that initiates the pathological pF4 antibodies," explains Professor Gordon.
"Indeed, the pathways of lethal antibody production in these disorders must be virtually identical and have similar genetic risk factors.
"Our findings have the important clinical implication that lessons learned from VITT are applicable to rare cases of blood clotting after adenovirus (a common cold) infections, as well as having implications for vaccine development," he says.
More information: Jing Jing Wang et al, Antibody Fingerprints Linking Adenoviral Anti-PF4 Disorders, New England Journal of Medicine (2024). DOI: 10.1056/NEJMc2402592
Journal information: New England Journal of Medicine
The Biden Administration will end a program which provides free COVID-19 vaccines to uninsured adults.
On Wednesday, the Centers for Disease Control and Prevention announced that the CDCs Bridge Access Program for COVID-19 Vaccines will end in August of 2024. The program has provided over 1.4 million free COVID-19 vaccines since September 2023.
After August, there may be a small amount of free vaccine available through health department immunization programs, but supply would be very limited, said CDC spokesperson David Daigle We dont yet know if the manufacturers will have patient assistance programs.
In the programs place, Daigle only offered the promise of the CDCs Vaccines for Adults proposal, which would provide non-influenza vaccines to 24 million uninsured adults. The public health proposal is currently part of President Joe Bidens 2025 budget, he said.
If enacted by Congress, this program would reduce disparities, protect communities from vaccine-preventable diseases, and enhance and maintain the infrastructure needed for responding to future pandemics, he said.
The decision is a strong reversal for the Biden administration, which previously stated in the run up to the 2020 election that, No one should pay a dollar out of pocket for coronavirus testing or treatment.
Over the course of Bidens presidency, the government has steadily weakened federal COVID-19 restrictions and guidance as a response to a decrease in hospitalizations and deaths, and an increase in so-called herd immunity. In March, the CDC reversed its recommendation that those with COVID-19 undergo a five-day isolation period.
However, health experts say that fewer people are keeping up with updated immunizations, leading to more needless deaths, as Americans of all ages continue to develop debilitating long-term symptoms.
A new analysis of pre-vaccine data from scientists at the Centers for Disease Control and Prevention (CDC) shows that 18% of hospitalized patients and 44% of those admitted to an intensive care unit (ICU) for COVID-19 died, with wide variations among different groups.
The study was published yesterday in Emerging Infectious Diseases and is based on 2,479,423 cases from 21 jurisdictions with hospitalization information reported to the CDC from May 1, 2020, to December 1, 2020, to create a hospitalization dataset. The authors also analyzed 4,708,444 cases from 22 jurisdictions for a death dataset during the same time frame. The case-hospitalization dataset covers 25.5% of the US population, and the case-fatality dataset covers 43.7% of the US population, the authors said.
Before the mid-December 2020 introduction of COVID-19 vaccines, the pandemic caused approximately 480,000 hospitalizations, and 350,000 deaths in the United States.
"Few precise estimates of hospitalization and mortality rates exist in the COVID-19naive population in the United States, especially among demographic and clinical subgroups," the authors said.
The overall case-hospitalization rate among patients was 5.7%, and the rate by sex was 6.2% for male and 5.2% for female. Hospitalization rates were lowest for children ages 5 to 14 (0.6%), and highest in case-patients 75 years and older (25.9%).
When looking at racial and ethnic demographics, the highest case-hospitalization rates were among African American or Black (14.0%) and Asian or Pacific Islander (11.2%) patients. White patients had the lowest rate (6.8%).
Few precise estimates of hospitalization and mortality rates exist in the COVID-19naive population in the United States.
In the deaths dataset, the overall case-fatality rate was 1.7%. The lowest death rates were seen in infants and young children (0.05% for infants and 0.01% for children 1 to 14 years of age). Ten infants died in the study period.
Case-fatality rates increased steadily with age. The rate was 4.7% in patients 65 to 74 years old, 12.0% in those 75 to 84, and 23.6% in people 85 and older.
Case-fatality rates for female patients were lower than or equal to those for male patients in every age-group except infants, the authors said.
Asian or Pacific Islanders had the highest crude mortality rate (3.0%), followed by Black and African Americans (2.8%).
The fatality rate was 0.6% in people who were not hospitalized. The rate was 17.6% among all people who were hospitalized and 44.2% in those admitted to an ICU.
"Age was a primary driver of SARS-CoV-2 hospitalization and death; rates had a U-shaped curve, being higher in infants, lowest in children 5 to 14 years of age, and highest among persons >65 years of age, confirming previous reports, " the authors concluded.
The analysis confirmed prior studies that have shown a nearly 50% mortality rate for ICU patients early in the pandemic. Moreover, the authors said, the findings present a baseline of data for future comparisons.
Mumbai: Earlier today, The Economic Times published a story that a third of the participants of an observational study on the side effects of Bharat Biotech's COVID-19 vaccine Covaxin reported adverse events of special interest (AESI), according to a report on SpringerLink.
As per the report, researchers found that female adolescents and those with a history of allergy were at a higher risk of AESI after receiving Covaxin. Of the 1,024 individuals enrolled, 635 adolescents and 291 adults could be contacted during the one-year follow-up. According to the study, 304 (47.9 per cent) adolescents and 124 (42.6 per cent) adults reported viral upper respiratory tract infections.
continued below
Recently, there has been a whirlwind of reports on several COVID-19 vaccines and their adverse events globally. AstraZeneca has admitted that its jab causes a rare side effect and is withdrawing its vaccine worldwide. The company has already withdrawn its EU marketing authorisation for the vaccine, which was branded Vaxzevira in Europe and Covishield in India and manufactured by the Serum Institute of India (SII).
Another report titled 'COVID-19: Two rare vaccine side effects detected in large global study' published in Vaccine, confirmed previously identified rare safety signals for myocarditis and pericarditis after a mRNA vaccine (Pfizer and Moderna) and Guillain-Barr syndrome and cerebral venous sinus thrombosis (CVST) after viral vector vaccines (AstraZeneca).
These recent studies highlight notable adverse events globally caused by COVID-19 vaccines, regardless of the technology and manufacturer. Bharat Biotech has emphasised the need for more comprehensive data to ensure unbiased and informative safety evaluations. Several studies have reported rare side effects from AstraZeneca's vaccine and mRNA vaccines by Moderna and Pfizer.
This underscores the ongoing need for rigorous safety monitoring and transparent reporting. Ensuring the safety of not only COVID-19 vaccines but every vaccine that is approved remains paramount, and continued research is crucial for improving vaccine safety and public confidence. Manufacturers need to take patient safety as a top priority when developing vaccines.
Weeks after pharmaceutical giant AstraZeneca admitted to rare side effects from its Covid-19 vaccine, an American woman, who had taken part in the clinical trials of the coronavirus shot, has sued the English pharmaceutical giant claiming that it had left her permanently disabled.
According to a report by The Telegraph,Brianne Dressen, a 42 year-old former American teacher from Utah, is first from the US to file a lawsuit against the company. In the UK, more than 50 people have filed a case against the corporation as multiple cases of rare and serious conditions were registered post taking the jab.
Last week, AstraZeneca voluntarily withdrew from the marketing authorisation of the COVID vaccine in EU. This came in action after the giant accepted that the vaccine can cause rare side effects to the human body in the court documents.
Ms Dressen mentioned that post the trial in 2020 she came down with a severe neurological condition which left her experiencing pricking pain all over her body.
Express Opinion | Side effects of AstraZeneca vaccine: Medicine is clear now to the courts
Speaking to Telegraph she stated that she was diagnosed with peripheral neuropathy and the her condition was considered as a "post-vaccine neuropathy".
This thing took me out of my job Im still permanently disabled,, she exclaimed.
I still have that horrific nightmare of the pins and needles sensation coursing through my body, head to toe, 24 hours a day, seven days a week.
Her complaint in the court further described that she had become "a shadow of her former self: unable to work, unable to do any athletic activity, unable to parent the way she had, and unable to drive more than a few blocks at a time"
In a chat thread on X(formerly twitter), Dressen shed light on what her current medication prevailed and how her 11 year-old son helped her set it up.
She mentioned that the conglomerate had signed an agreement with her stating they will "pay the costs of medical treatment for research injuries, provided that the costs are reasonable, and you did not cause the injury yourself". However, the case comes to light after the court papers were filed on May 12 where the company did not adhere to the promises made.
From the body of evidence in clinical trials and real-world data, the AstraZeneca-Oxford vaccine has continuously been shown to have an acceptable safety profile and regulators around the world consistently state that the benefits of vaccination outweigh the risks of extremely rare potential side effects, stated an AstraZeneca spokesperson through an email communication on May 13.
Current Neurology and Neuroscience Reports journal in 2023 published a finding greater than expected occurrence of severe neurological adverse events following different kinds of Covid-19 vaccination. However, they said that the evidence was not too strong for the withdrawal of the vaccine.
Express Opinon | Covishields rare side-effects: In election season, dangers of politicising the vaccine
Ms Dressen has filed the case in Utah court which allows the complainant to incur amount for breach and damages. While she hasn't specified any amount, she holds the legally binding bills of tens of thousands of dollars for medical care that she had to take care of. Ms Dressen in a X (formerly twitter) post mentioned that the company offered $1200 as a settlement.
In addition, Dressen mentioned that the biggest impact of this condition was on her children who are aged nine and eleven.
They dont remember who I was before, already, she added.
Apart from the breach of contract she is also suing the company for emotional distress, legal fees and lost income.
Hindsight is 20:20, but at the time, I really genuinely believed that this would be like our generations moment to show how we can overcome adversity. I really did. she exclaimed.
