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Boxes of Johnson & Johnson's Janssen COVID-19 vaccine at a vaccination site in Florida.
Enlarge / Boxes of Johnson & Johnson’s Janssen COVID-19 vaccine at a vaccination site in Florida.

A panel of expert advisors for the Centers for Disease Control and Prevention on Friday voted 10 to four (with one abstention) in favor of lifting the pause on the Johnson & Johnson COVID-19 vaccine. The panel reaffirmed its recommendation for use of the one-shot vaccine in adults of all ages and sexes.

The reaffirmation will come with a new warning in the Food and Drug Administration’s emergency use authorization, which will note that the vaccine appears linked to an extremely rare—but life-threatening—condition that involves serious blood clots and low blood platelets, mainly in women younger than age 50. Experts have dubbed the condition “thrombosis with thrombocytopenia syndrome,” or TTS.

In a day of data presentations, analyses, and discussion, the panel—the Advisory Committee on Immunization Practices (ACIP)—heard all of the risks and benefits of resuming use of the vaccine or restricting its use in certain populations, such as in younger people.

Overall, ACIP firmly determined that the benefits of the vaccine easily exceeded the risks, particularly as coronavirus variants continue to spread and medical experts are only beginning to understand the constellation of outcomes and long-term symptoms of COVID-19.

“We need as many people to be vaccinated as possible in order to reach community immunity and put the pandemic behind us,” Henry Bernstein, ACIP voting member and professor of pediatrics at Zucker School of Medicine said in the meeting. “The J&J vaccine will help us do just that.”

Of the 7.98 million doses of Johnson & Johnson’s vaccine administered, there have been 15 confirmed cases of TTS as of April 21. All of the 15 cases were in women between the ages of 18 and 59. However, there was one case of TTS retrospectively identified in a 25-year-old man who participated in an earlier clinical trial.

Of the 15 TTS cases that occurred after authorization, three women died and seven remained hospitalized, with four of those in the intensive care unit (ICU). The remaining five have been discharged.

Breaking down the data further, CDC scientists found that 13 of the 15 TTS cases were in women ages 18 to 49 and that those occurred among 1,866,294 Johnson & Johnson vaccine doses administered to women in that age group. That amounts to a reporting rate of 7 TTS cases per million vaccinated women in that age group. In women ages 50 and above, there were 2 cases of TTS among 2,125,239 doses administered, for a reporting rate of 0.9 per million vaccinated.

Risks and warnings

In contrast, the ACIP heard modeling data today that suggested what would happen if use of the Johnson & Johnson vaccine resumed. Among women ages 18 to 49, the vaccine would prevent 12 COVID-19 deaths and 127 COVID-related ICU admissions per one million women vaccinated in that age group in a six-month period. Among women ages 50 and above, the vaccine would prevent 593 deaths and 1,292 ICU admissions.

Voting members of the ACIP had no doubt that the vaccine’s overall benefits outweighed the risks. Though several members reaffirmed their support for the 11-day pause in use and noted that it allowed them time to review more data and analyses, support for resuming vaccine use at this time was overwhelming.

There were four ACIP members who voted “no” on reaffirming the recommendation for use in all adults. However, they largely did so out of a desire to offer more guidance on the warning of TTS, primarily aimed at women in younger age groups.

“I did not object to the recommendation; I objected to the absence of any kind of guidance from us,” Sarah Long, ACIP voting member and professor of pediatrics at Drexel University College of Medicine said directly after her “no” vote. “This is an age group that is most at risk [of TTS] that is getting a vaccine predominately to save other people’s lives and morbidity—not their own…I’m very sorry that we haven’t chosen to put up front the knowledge that we have that this is unique, it’s clustered, it’s almost certainly related to the vaccine, and there are options.”

Pablo Sánchez, professor of pediatrics at Ohio State University, echoed the concern. “I have no problem with the continued availability of this vaccine,” he said after his “no” vote. But “I think we have to have stronger language and make sure that people are informed appropriately,” he said.

Pediatrics professor Grace Lee of Stanford offered a counterpoint in support of not having such an additional warning. “I actually agree with all of my colleagues who voted no—I absolutely think that [TTS] is a serious adverse event,” she said. “But I also think that we have to come out with a clear recommendation.” Having a recommendation that both recommended use of the vaccine for all adults but warned that younger women may choose not to use the vaccine “would have been confusing,” she said.

The CDC will now have the final say on the ACIP’s recommendation and, if it agrees, move forward with resuming vaccinations and providing information to healthcare providers and members of the public on the risks and benefits of the vaccine.

The Emergent BioSolutions plant, a manufacturing partner for Johnson & Johnson's COVID-19 vaccine, in Baltimore, Maryland, on April 9, 2021.
Enlarge / The Emergent BioSolutions plant, a manufacturing partner for Johnson & Johnson’s COVID-19 vaccine, in Baltimore, Maryland, on April 9, 2021.

Things are not looking good for Emergent BioSolutions, the contract manufacturer that ruined 15 million doses of Johnson & Johnson’s one-shot COVID-19 vaccine and millions more doses of AstraZeneca’s COVID-19 vaccine at its production facility in Baltimore.

The Food and Drug Administration on Wednesday released a searing inspection report of the facility, finding a slew of significant violations and failings.

Meanwhile, federal lawmakers have opened a multi-pronged investigation into whether Emergent used ties to the Trump administration to get billions of dollars in federal contracts despite a history of failing to complete contracts, inadequately training staff, persistent quality-control issues, and an “unjustified” 800% price increase for an anthrax vaccine.

In a letter sent to Emergent’s top executives Tuesday, Rep. Carolyn Maloney, chairwoman of the House Committee on Oversight and Reform, and Rep. James Clyburn, chairman of the Select Subcommittee on the Coronavirus Crisis, laid out the investigation, writing:

Emergent received $628 million in June 2020 to establish the primary US facility for manufacturing vaccines developed by Johnson & Johnson and AstraZeneca. Dr. Robert Kadlec, who served as Assistant Secretary for Preparedness and Response under President Trump and previously worked as a consultant for Emergent, appears to have pushed for this award despite indications that Emergent did not have the ability to reliably fulfill the contract.

800% drain

But the investigation stretches back much farther than the start of the pandemic—through years of questionable federal contracts.

In 1998, Emergent (then called BioPort) bought the license to an anthrax vaccine. The vaccine, BioThrax, was approved by the FDA in 1970 but remains the only FDA-approved vaccine for anthrax. As such, Emergent is the sole supplier of anthrax vaccine for the federal government’s Strategic National Stockpile (SNS). When Emergent bought the vaccine in 1998, a dose went for about $3.35. By 2010, the price was up to $28 a dose. Now, the price is over $30, and average wholesale prices are even higher, reaching $90 per dose, the lawmakers note.

“Emergent has raised the government purchasing price of the anthrax vaccine by 800% since acquiring the drug in 1998,” the lawmakers write in their letter. “As a result, through most of the last decade, nearly half of the SNS’s budget has been spent purchasing Emergent’s anthrax vaccine. These spiraling costs contributed to shortages of critical supplies, including ventilators, reusable respirator masks, and other personal protective equipment, which severely impacted the government’s ability to respond to the coronavirus crisis.”

This drain on the SNS budget was particularly apparent during the pandemic—which Robert Kadlec, the former Emergent consultant, himself acknowledged.

Kadlec was nominated in 2017 by President Trump to lead the Office of the Assistant Secretary for Preparedness and Response (ASPR). Following his confirmation, Emergent received millions of dollars in federal contracts from ASPR, including contracts for the SNS that were awarded without competitive bidding, the lawmakers note in their letter.

In 2020—just before the pandemic hit the US—Kadlec’s office awarded Emergent around $3 billion in long-term contracts for anthrax and other bioterrorism threats. According to the lawmakers, Kadlec later suggested this was a bad move, saying: “If I could spend less on anthrax replenishment, I could buy more N95s. I could buy more ventilators. I could buy more of other things that quite frankly I didn’t have the money to buy.”

Failures and an inspection

Aside from the skyrocketing prices, the lawmakers suggest Emergent didn’t even deserve the contracts in the first place. In 2012, the Department of Health and Human Services awarded Emergent a $163 million contract to renovate its (currently troubled) Baltimore manufacturing plant. The idea was for the plant to become a manufacturing hub for rapidly producing vaccine in the event of an infectious disease outbreak or bioterror attack. Part of the contract stipulated that Emergent would be required to do a test run, producing 50 million doses of a pandemic influenza vaccine in the span of four months, and obtain manufacturing approval from the FDA by June 2020.

Emergent failed to meet those requirements.

Reading the FDA’s inspection report of Emergent’s Baltimore facility, it’s clear why. During the nine-day inspection, which ended April 20, FDA inspectors logged a long list of problems at the facility.

First on the list is that Emergent failed to thoroughly investigate how the millions of Johnson & Johnson and AstraZeneca doses became contaminated. The agency concluded that, without a thorough review of what happened, it’s possible that other finished batches of vaccine may also be ruined. “There is no assurance that other batches have not been subject to cross contamination,” the inspectors wrote.

The FDA inspectors went on to note unsanitary conditions, paint peeling off of the walls and floors, residue on equipment, improperly trained staff, and numerous opportunities for vaccine products to be contaminated.

The potential for cross contamination—spread of viral ingredients back and forth between Johnson & Johnson’s vaccine and AstraZeneca’s vaccine—appeared rampant at the facility. Inspectors witnessed Emergent employees dragging unsealed, non-decontaminated bags of medical waste across different manufacturing areas. In some cases, employees tossed bags of medical waste, unsealed, into a service elevator. Emergent did not have proper written procedures for how to decontaminate waste, the inspection report notes. Security footage also caught employees moving from different areas of the facility without following proper procedures for donning and removing protective gowns.

At the request of the FDA, vaccine production at the Baltimore facility has been halted since April 16.

In a statement Wednesday, Emergent said that the FDA’s findings “provide direction on the necessary steps to improve operations.” The company went on:

The FDA’s feedback will help us continue to improve and strengthen the supply chain for Johnson & Johnson’s COVID-19 vaccine. While we are never satisfied to see shortcomings in our manufacturing facilities or process, they are correctable and we will take swift action to remedy them.

A large streetside sign for a Johnson and Johnson vaccine.
Enlarge / General exterior view of the head office of Janssen pharmaceutical company on April 15, 2021 in Leiden, Netherlands.

About 88 percent of Americans support the pause of Johnson & Johnson’s COVID-19 vaccine, and the pause did not increase vaccine hesitancy, according to fresh data from the Axios-Ipsos Coronavirus poll.

The finding is likely to hearten public health experts, who have faced criticism and concern that the pause could erode confidence in vaccine safety and fortify already high-levels of vaccine hesitancy in the country.

The Centers for Disease Control and Prevention, along with the Food and Drug Administration, recommended a pause in the use of the Johnson & Johnson vaccine on April 13 after linking the one-dose vaccine to six cases of a rare blood-clotting condition, one of which was fatal. The six cases occurred among more than 6.8 million people given the vaccine, suggesting that if the blood clots are, in fact, a side effect of the vaccine, they are an extremely rare side effect.

Many experts defended the pause by arguing that the hiatus and full evaluation of the potential serious side effect—even if it’s only a one-in-a-million occurrence—prove that stringent safety monitoring and precautions are in place. Americans largely appear to agree.

In the latest poll, the market research firm Ipsos first asked if people had heard of the pause. An impressive 91 percent of respondents said they had. Of those who said they were aware of the pause, 88 percent responded “Yes” to the question: “Do you believe the FDA and CDC are being responsible by recommending a pause on the distribution of the Johnson & Johnson vaccine?”

The poll was conducted between April 16 and 19 by Ipsos, which drew on a nationally representative probability sample of 1,033 general population adults, ages 18 or older. For questions posed to all 1,033 people, the margin of sampling error is ±3.3 percentage points at the 95 percent confidence level.

Impotent pause

The poll also suggested that the Johnson & Johnson pause has not increased or decreased vaccine hesitancy.

As in every other previous poll going back to last August, Ipsos pollsters asked everyone: “How likely, if at all, are you to get the first-generation COVID-19 vaccine, as soon as it’s available?” A total of 70 percent said they were likely to get a vaccine or had already gotten a vaccine, while a total of 30 percent said they were “not very likely” or “not at all likely” to get a vaccine.

The total of 70 percent in the “likely/already had” category is basically unchanged from recent polls. In the poll conducted between April 2 and 5, a total of 71 percent of respondents fell into that category, while the total was 69 percent during the poll conducted between March 19 and 22. The same lack of change was seen in the “not likely” category, which also wobbled between an insignificantly different 29 percent and 30 percent in the two previous polls.

Moreover, the numbers are significantly better than the peak of vaccine resistance seen in a late September poll. That’s when only 37 percent said they were likely to get vaccinated and 63 percent said they were not likely to get vaccinated.

Cliff Young, president of Ipsos US Public Affairs, told Axios that “People are unfazed” by the Johnson & Johnson vaccine pause. “The way forward is about the vaccine, so if there’s any stumble, people are going to pay attention to it—but it hasn’t had an impact thus far” on people’s willingness to get the vaccine.

“Not sustainable”

The same results were found in a focus group of vaccine-hesitant Trump voters, according to a report by The Washington Post. Frank Luntz, a longtime GOP communications expert, held the focus group over Zoom on Sunday, involving 17 conservative participants. Throughout the pandemic, Republicans and conservatives have been among the most consistent groups to tell pollsters that they are unwilling or hesitant to get a COVID-19 vaccine. In a recent Kaiser Family Foundation poll, a total of 35 percent of Republicans surveyed said they would definitely not get vaccinate or only get vaccinated if vaccination was required.

The Johnson & Johnson vaccine pause is not changing their thinking one way or the other, according to the focus group. The group largely shrugged off the pause and questioned why the CDC and FDA halted use for a potential side effect that is so rare, the Post reported. “A lot of people might want to take the Johnson & Johnson vaccine versus the others, because it’s one shot versus two,” said a focus-group participant identified as Cathy from Pennsylvania. An epidemiologist who helped convene the focus group further noted to the Post that “we didn’t see folks really concerned with the pause in the J&J vaccine.”

Instead, focus group members were more concerned about recent reports that Pfizer CEO Albert Bourla suggested people may need to get a COVID-19 booster shot within a year. “I feel like this is not going to end,” said a focus-group participant identified as Erzen from New York. “I mean, we’re just going to be shot up and shot up and shot up. We can’t live like this. This is not sustainable.”

The Emergent BioSolutions plant, a manufacturing partner for Johnson & Johnson's Covid-19 vaccine, in Baltimore, Maryland, on April 9, 2021.
Enlarge / The Emergent BioSolutions plant, a manufacturing partner for Johnson & Johnson’s Covid-19 vaccine, in Baltimore, Maryland, on April 9, 2021.

The US Food and Drug Administration last week asked Emergent BioSolutions to stop making Johnson & Johnson’s COVID-19 vaccine at its troubled facility in Baltimore, according to a regulatory filing Emergent released Monday.

The FDA had begun an inspection of the contract manufacturer’s facility on April 12 but requested on April 16 that production be halted “pending completion of the inspection and remediation of any resulting findings,” the filing reads. Any vaccine materials already made at the plant will be held in quarantine.

The production halt follows news last month that a mishap at the plant led to the ruin of 15 million doses of Johnson & Johnson’s one-shot COVID-19 vaccine. The ruined doses had reportedly been contaminated with ingredients from AstraZeneca’s COVID-19 vaccine, which was also being manufactured at the plant at the time.

The accident was a major stumbling block for Johnson & Johnson’s vaccine production—but not a consumer safety issue. All of the doses of Johnson & Johnson’s vaccine that has been used in the US so far have been produced in the Netherlands. The Emergent facility in Baltimore had not yet been authorized by the FDA for vaccine production when the doses were ruined, and none of the spoiled doses completed the production process.

Early this month, the Biden administration put Johnson & Johnson in charge of the facility and ordered AstraZeneca’s vaccine production out to prevent further cross-contamination problems. At the time, the company said that, despite the setback, it still expected to meet its commitment to deliver nearly 100 million doses of its vaccine to the US government by the end of May. But the current production pause again raises questions of whether the company will still be able to meet that goal.

“At this time, it is premature to speculate on any potential impact this could have on the timing of our vaccine deliveries” the company told Reuters.

In a statement to Politico, Emergent said:

While we await the FDA’s full feedback, we are working with J&J and the FDA on strengthening the supply chain for this vitally important vaccine… We acknowledge that there are improvements we must make to meet the high standards we have set for ourselves and to restore confidence in our quality systems and manufacturing processes.

Pause beyond pause

For now, Biden officials say they have enough vaccine supply from Moderna and Pfizer-BioNTech to continue the current pace of vaccinations, which has exceeded 3 million doses a day recently.

Regardless of the production pause, use of Johnson & Johnson’s vaccine was already on pause as federal health experts and advisors review data linking the vaccine to an extremely rare but dangerous blood-clotting condition.

Last week, the FDA and the Centers for Disease Control and Prevention said that, out of more than 6.8 million vaccine doses administered, they had identified six cases of the unusual condition, which leads to dangerous life-threatening blood clots in combination with low levels of platelets. One person died of the condition, and another was said to be in critical condition.

A vaccine advisory committee for the CDC, called ACIP, held an emergency meeting last week but punted on making any recommendations for use of Johnson & Johnson’s vaccine going forward. Instead, the committee scheduled another public meeting for this Friday, April 23 from 11 am to 5 pm EDT where it will review further data and analyses.

In a White House press briefing Monday, CDC director Rochelle Walensky said that the agency had received additional reports of blood-clotting cases possibly linked to the vaccine.

There have been “a handful of cases, not an overwhelming number of cases,” Walensky said in the briefing. “We are working through and adjudicating them and verifying whether they do in fact reflect a true case.” The CDC and the FDA will then present their findings to ACIP on Friday, she said.

Boxes of Johnson & Johnson's Janssen COVID-19 vaccine at a vaccination site in Florida.
Enlarge / Boxes of Johnson & Johnson’s Janssen COVID-19 vaccine at a vaccination site in Florida.

An advisory committee for the Centers for Disease Control and Prevention declined to vote on the fate of Johnson & Johnson’s COVID-19 vaccine Wednesday, likely leaving in place a pause on the vaccine’s use until the committee reconvenes in seven to 10 days.

The CDC’s Advisory Committee on Immunization Practices, or ACIP, expects that the coming week or so will provide additional data and analyses on the vaccine’s potential risks. Until it has more information, ACIP opted to provide no new recommendations on the use of the vaccine.

On the table, however, was everything from recommending against use of the vaccine altogether; recommending that only certain groups receive the vaccine, such as only men or only people over a certain age; or recommending that the pause be lifted and use continue in all adults as before.

In a hearty discussion Wednesday afternoon, ACIP members said they simply didn’t feel they had enough information on updated vaccine risks to vote one way or the other on any of the possible usage recommendations.

Emergency pause

ACIP gathered for the emergency meeting Wednesday after the CDC and the Food and Drug Administration abruptly announced on Tuesday that they were pausing use of the Johnson & Johnson vaccine. The agencies linked the vaccine to six illnesses involving an unusual combination of dangerous blood clots and low platelet levels. One person died from their condition and another is in critical condition.

The cases are extremely rare, with the six occurring among more than 6.8 million people vaccinated with the Johnson & Johnson vaccine. However, the cases closely resemble a very rare side effect seen in some people who have received AstraZeneca’s COVID-19 vaccine, which uses a similar adenovirus-based vaccine design.

With both vaccines, authorities noted unusual cases of cerebral venous sinus thrombosis (CVST), coupled with low blood levels of blood platelets (thrombocytopenia). CVST is a rare type of stroke in which a clot prevents blood from draining out of the brain. Platelets are the cell fragments in blood that stick together to form clots. Typically, low levels of platelets lead to bleeding, not clotting conditions, like CVST. In fact, it’s such an unusual combination that it’s unclear how often CVST even occurs in combination with thrombocytopenia in the absence of the vaccines. As such, researchers and public health experts have struggled to estimate the potential increased risk of developing this combination after taking either of the vaccines.

However, there’s a clear pattern emerging in these extremely rare, vaccine-linked cases—and researchers speculate that the vaccines may be triggering an aberrant immune response. A similar condition is seen rarely in patients given the blood thinner heparin. For reasons researchers don’t entirely understand, a small number of patients given heparin produce antibodies that attack a common platelet protein called Platelet Factor 4, or PF4. These antibodies activate platelets, leading to a hyperclotting state, while also promoting platelet clearance, dragging down platelet levels.

Case details

So far, many of the people who developed blood clots and thrombocytopenia after receiving the AstraZeneca vaccine also tested positive for antibodies against PF4, even though they were not given heparin. In the ACIP meeting today, CDC researchers noted that five of the six people with clotting cases linked to the Johnson & Johnson vaccine also tested positive for antibodies against PF4. The sixth case wasn’t tested.

There were other intriguing details revealed in the meeting as well. All six of the cases reviewed by the CDC and FDA were in white women between the ages of 18 and 48. This has led some people to speculate that for these women in the child-bearing age range, the blood clots could be related to the use of birth control pills, which carry their own risk for clotting. However, according to the data discussed in the ACIP meeting, only one of the six affected women was taking birth control pills.

Moreover, an analysis by scientists at Johnson & Johnson found a seventh case of CVST with thrombocytopenia in one of their clinical trial participants—a male participant. The previously healthy 25-year-old man developed CVST, low blood platelets, and tested positive for anti-PF4 antibodies after taking the vaccine.

To date, CDC researchers and other scientists have found no obvious pattern of risk factors for developing the life-threatening blood clots and low platelet levels.


But, CDC researchers and ACIP members expect they may see more cases emerge in the coming days. As noted in today’s meeting, the combination of CVST and thrombocytopenia tends to occur six to 13 days after vaccination. However, a little more than half of all doses of Johnson & Johnson vaccine that have been administered in the US to date were administered in the past two weeks. Specifically, prior to March 30, there were 3.47 million Johnson & Johnson doses administered in the US, or 48 percent of all doses administered to date. Between March 30 and April 13, there were 3.77 million doses administered, or 52 percent of all doses administered. That suggests that, despite the pause in vaccine use, there may be more cases detected in the coming weeks, particularly with lags in clinical reporting.

With the sparse data analysis so far and the potential for more cases and data to arise shortly, the ACIP opted to hold out a little longer before making any recommendations. Their position is a difficult one. They’re trying to balance safety concerns with the urge to vaccinate people as quickly as possible against the deadly pandemic coronavirus, particularly as virus variants emerge and spread. They were also sensitive to the reality that the adenovirus-based vaccines (made by Johnson & Johnson, AstraZeneca, and others) are more likely to be used in vulnerable populations and developing countries. The pauses and drama around these vaccines in places like the US and EU could increase vaccine hesitancy in populations with few other vaccine options.

For the US population overall, however, CDC researchers noted in the meeting today that the country’s vaccine supply is still strong. Even with the extended Johnson & Johnson pause, the US has steady supplies of mRNA vaccines from Moderna and Pfizer-BioNTech.

Image of a woman receiving a vaccine.
Enlarge / A nurse practitioner named Heidi Johnson administers a vaccine from Johnson & Johnson.

On Tuesday morning, the US Centers for Disease Control and Food and Drug Administration issued a release acknowledging an extremely rare clotting disorder was associated with the use of the Johnson & Johnson COVID vaccine. The problem is actually less than a one-in-a-million issue; in data from the US, where 6.8 million doses of this vaccine have been used, there have only been six instances of the clotting problem detected.

Because the clots call for an unusual treatment, however, the organizations are calling for a pause in administering the shot. This will provide them with time to ensure the medical community is aware of the appropriate treatment.

This is not the first vaccine to create extremely rare clotting issues. They’ve also been seen following use of the AstraZeneca vaccine. The problem appears to be caused by the harmless virus (an Adenovirus) that carries a single gene from SARS-CoV-2 in order to elicit an immune response.

Apparently, in very rare cases, the Adenovirus triggers an immune response to factors found on the surface of platelets, which are an essential part of the clotting process. This activates platelets, causing clots, and at the same time reduces the total platelet count.

These seemingly contradictory changes make treating it through the normal approach to excessive clotting dangerous. Typically, the appearance of clots would call for using a treatment that would reduce the probability of clots forming. But, due to the low platelet counts in these individuals, those treatments can make it much less likely that clots form when they’re needed.

It’s this difference between apparent patient needs and appropriate treatment that has caused the CDC and FDA to call for a pause in the use of the J&J vaccine.

CDC will convene a meeting of the Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution. This is important, in part, to ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot.

The CDC and FDA highlight severe headache, abdominal pain, leg pain, or shortness of breath as potential symptoms of the clotting problem.

So far, all six cases have occurred among women below the age of 50 and appeared between one and two weeks after vaccination. Because of the rarity of the clotting disorder compared to the very large risks posed by COVID-19, most countries that initially suspended the use of the AstraZeneca vaccine re-started it with added precautions. Germany, for example, is using it for patients over 60, since they are at lower risk of clots and much higher risk of severe COVID-19.

It’s likely that the US will also resume use of the J&J vaccine, which still has an excellent overall safety profile, typically has lower side effects than two-dose vaccines, and is extremely effective.

Unfortunately, the US also has a large population of people who are hesitant about receiving any vaccines. Given their persistent worries, these events will likely feed into their paranoia. And their apparent resistance to facts will make it much harder for them to evaluate the risk calculation of an extremely rare side effect in a vaccine against a virus that’s frequently deadly.

Extreme close-up photo of small, clear vials.
Enlarge / Vials of the AstraZeneca COVID-19 vaccine are seen during the opening of a vaccination center in Cyprus on March 22, 2021.

European medical regulators on Wednesday concluded that there is a strong link between AstraZeneca’s COVID-19 vaccine and life-threatening conditions involving the unusual combination of blood clots and low levels of blood platelets.

As such, the conditions should be listed as a “very rare side effects” of the vaccine, according to the European Medicines Agency, a regulatory agency of the European Union.

The conclusion was based on the EMA’s in-depth review of 86 blood-clotting events among around 25 million people vaccinated with the AstraZeneca vaccine in Europe and the UK. Of the 86 blood-clotting events, 18 people died. Most—but not all—of the cases occurred in women under the age of 60.

The events reviewed by the EMA included 62 cases of cerebral venous sinus thrombosis (CVST), a rare form of stroke in which a clot prevents blood from draining out of the brain. The remaining 24 cases involved splanchnic vein thrombosis, which involves blood clots in the veins that drain blood from the abdomen.

Beyond the 86 cases examined, the EMA estimated that there’s a reporting rate of one case of the side effect in 100,000 people vaccinated.

Curious cause

Oddly, the clotting events have been accompanied by low levels of blood platelets, which are the blood cell fragments that stick together to form clots. Typically, low platelets lead to increased bleeding, not clotting. Regulators noted that this unusual combination resembles a condition called heparin-induced thrombocytopenia or HIT. In rare cases, patients who are given heparin—an anticlotting drug—see a drop in their platelets yet go into a hyperclotting state, which can lead to widespread clotting and death.

HIT develops because of an aberrant immune response. In a reaction to heparin that’s not completely understood, some patients’ immune systems produce antibodies that attack a common platelet protein called Platelet Factor 4, or PF4. This in turn triggers platelet activation and pro-clotting particles, leading to HIT.

Some researchers suspect that the blood-clotting events linked to AstraZeneca’s vaccine may also be down to a similar berserk immune response—and it may be treatable. Extremely preliminary data—posted online but not yet published in a journal or peer-reviewed—hints that the rare condition in some vaccinees could be treated with nonheparin anticlotting drugs as well as a high-dose of immunoglobulin, which has been shown to inhibit platelet activation in HIT patients.

In its announcement Wednesday, the EMA noted that recognizing the early signs of blood clots and low platelets are critical, and getting specialized treatment quickly can avoid serious outcomes.

The EMA noted that recently vaccinated people should watch out for:

  • shortness of breath
  • chest pain
  • swelling in your leg
  • persistent abdominal (belly) pain
  • neurological symptoms, including severe and persistent headaches or blurred vision
  • tiny blood spots under the skin beyond the site of injection

As seen in people who develop HIT after heparin, the blood-clotting events and low platelets seen in vaccinees usually develop within two weeks of getting their first dose.

Though the EMA solidified the connection between the clots and the AstraZeneca vaccine, it still recommends using the vaccine. “The reported combination of blood clots and low blood platelets is very rare,” the agency noted, “and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.”

AstraZeneca drama

The conclusion follows weeks of drama around the vaccine, in which more than a dozen countries that had already authorized the vaccine’s use abruptly halted vaccinations out of concern for the blood clots—then resumed use out of concerns for the spread of COVID-19.

Along with the EMA, World Health Organization still strongly contends that the benefits of the AstraZeneca vaccine’s effectiveness at preventing deadly COVID-19 infections strongly outweigh the risks of extremely rare blood-clotting conditions.

Nevertheless, Germany moved last week to restrict the vaccine’s use in people under age 60, the age group in which most—but not all—of the rare clotting events have occurred. And on Tuesday, the University of Oxford, which co-developed the vaccine with AstraZeneca, said that it had paused a small UK trial of the vaccine in children and teenagers.

Meanwhile, AstraZeneca has continued to be mired in communication bungles. In the latest misstep, the company got into a highly unusual and concerning spat with a panel of US experts tasked with overseeing its COVID-19 vaccine trial and data. The panel, called the Data and Safety Monitoring Board, claimed that AstraZeneca had cherry-picked the trial data results it trumpeted in a press release, potentially misleading the public on the vaccine’s true effectiveness.

The company has defended its actions but has not yet submitted its data to the US Food and Drug Administration in order to obtain an Emergency Use Authorization. Last week, top infectious disease expert Anthony Fauci suggested that, even if it is authorized, the US may not need AstraZeneca’s vaccine because it will have enough supply of the three vaccines already authorized for use in the US.

Trouble for Johnson & Johnson

The new side effect listing in the EU will only make things more difficult for AstraZeneca. And it’s also likely to cast a shadow over the Johnson & Johnson COVID-19 vaccine, which is authorized in the US and elsewhere and uses the same design as AstraZeneca’s vaccine.

Both vaccines use an adenovirus vector. Adenoviruses are common viruses that can cause cold-like infections and other mild illnesses in people. For vaccine delivery, they’re engineered so they can’t replicate in cells or cause disease, but they can deliver to cells the genetic code of a more dangerous germ. In the case of the COVID-19 vaccines, the engineered adenoviruses deliver the code of the SARS-CoV-2 spike protein, which adorns the outside of the virus’s particle. The spike protein is what SARS-CoV-2 uses to grab onto human cells and get inside—and it’s a key target for potent antibodies and other immune responses. Once the adenovirus vector delivers the code for spike, our cells can make their own versions of the protein and use it to train immune responses that will recognize and destroy the SARS-CoV-2 virus.

A potential pitfall of adenovirus-based vaccines is that adenoviruses can also bind to platelets and cause problems. In fact, some prepandemic data has suggested that adenoviruses can activate platelets and lead to low platelet counts. But the connection between this and the vaccine and the mechanism causing the blood clotting in vaccinees needs far more data to understand.

Still, the side effects seen in AstraZeneca’s vaccine raise worries for Johnson & Johnson’s. During the clinical trials of the Johnson & Johnson vaccine, there was an early sign of an increased risk of these blood-clotting conditions in vaccinated people, Peter Arlett, head of data analytics at the EMA, said in a press briefing Wednesday. But the link was never confirmed, he added.

Of the approximately 4.5 million people who have received the Johnson & Johnson vaccine worldwide, there have been three reported cases of blood-clotting events similar to those seen in people given the AstraZeneca vaccine, Arlett said. These numbers are “extremely small,” he emphasized. “This is, however, under close scrutiny… I think it would be fair to say there’s intensive monitoring of this issue across the vaccines.”