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Federal authorities on Tuesday recommended that states stop using Johnson & Johnson’s Covid-19 vaccine while an investigation is conducted into six serious cases of clotting problems — one of which was fatal — that were reported among women who received the vaccine.

The blood clots are similar to those reported by several European countries after use of AstraZeneca’s Covid-19 vaccine. And they are similar to an event that occurred during Johnson & Johnson’s U.S.-based clinical trial, an event that led to a temporary pause in that trial last fall. That case involved a man in his 20s, STAT reported at the time.

The clotting problem appears to be quite rare. As of Monday, more than 6.8 million doses of the Johnson & Johnson vaccine had been administered in this country. But officials acknowledged the investigation — and increased use of the vaccine, which was shipped in record numbers last week — could lead to the discovery of more cases.

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The concern over Johnson & Johnson’s vaccine is raising questions about whether there is what’s known as a “class effect” — a problem one would expect to see with all vaccines made in the way the J&J and AstraZeneca vaccines are made. The Sputnik V vaccine, made by Russia’s Gamaleya Research Institute and the vaccine made by CanSino, a Chinese manufacturer, are made in the same way as the Johnson & Johnson and AstraZeneca vaccines.

The four vaccines use modified adenoviruses — viruses that cause colds — to deliver instructions to human cells to make the SARS-CoV-2 spike protein, the exterior proteins that allow SARS-2 viruses to attach to and invade cells. Those vaccine-induced spike proteins teach the immune system to look out for and defend against SARS-2 viruses.

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Theories about the cause of the rare clotting issues hinge on the possibility that, in small numbers of people, the adenoviruses trigger an aberrant immune response. That, in turn, results in a rare combination of widespread clotting and low platelet counts.

Top officials of the Food and Drug Administration and the Center for Disease Control and Prevention stressed during a press conference Tuesday that clotting problems have not been seen with the vaccines made by Moderna and the Pfizer-BioNTech partnership. Roughly 180 million doses of those vaccines have been given so far in the country.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, skirted around the term “class effect” but suggested the fact that the problem was also seen with the AstraZeneca vaccine underscored for the FDA and CDC that the events might be linked to vaccination.

“I hesitate to call it a class effect,” Marks said. “But I think it is plainly obvious to us already that what we’re seeing with the Janssen vaccine looks very similar to what was being seen with the AstraZeneca vaccine.”

Janssen is the name of Johnson and Johnson’s vaccines division.

The CDC and the FDA jointly conduct surveillance for adverse events that might be linked to use of vaccines; the two agencies jointly announced the recommendation that use of the vaccine be paused. The move falls short of an order not to use the vaccine and Marks acknowledged that it may continue to be used in some cases, if a provider and a patient discuss the risks and benefits and decide to proceed with vaccination.

The CDC’s Advisory Committee on Immunization Practices, which advises the public health agency on vaccine uses, is holding a special meeting Wednesday to review the J&J data. It is conceivable that the panel of outside experts will suggest that use of the vaccine be continued, but with some restrictions on who should get this vaccine. A number of other countries in Europe and elsewhere have already imposed such limits on use of the AstraZeneca vaccine. That vaccine has not been authorized in the United States.

The FDA and CDC officials stressed the decision to pause use of the J&J vaccine was made “out of an abundance of caution.” Key to the decision was recognition of the need to inform health care providers to be on the lookout for people who might be having one of these reactions so that they can avoid giving care that could make the situation worse.

“The issue here with these types of blood clots, is that if one administers the standard treatments that we as doctors have learned to give for blood clots, one can actually cause tremendous harm or the outcome can be fatal,” Marks said. “One needs to make sure that providers are aware that if they see people who have low blood platelets, or if they see people who have blood clots, they need to inquire about the history of recent vaccination, and then act accordingly.”

In a statement, Johnson & Johnson said it is working closely with health authorities and medical experts to investigate the issue. It also announced it would delay the rollout of its vaccine in Europe.

Neither the statement from the agencies nor the statement from the company referenced the status of Johnson & Johnson’s ongoing clinical trial in the United States that is testing its vaccine in a two-dose regimen. The vaccine is currently authorized for use in a single dose.

When asked if the company has been asked to pause the trial, Marks said statements from the company would address voluntary actions the company is taking. J&J did not immediately respond to a request for comment from STAT.

The blood clots reported in the six cases are known as cerebral venous sinus thrombosis (CVST); in all cases, the clots were seen in combination with low levels of blood platelets, a condition known as thrombocytopenia. All occurred among women between the ages of 18 and 48, the statement from the CDC and FDA said, and symptoms occurred between six and 13 days after vaccination. In addition to the fatal case, one of the women is in critical condition.

Experts applauded the decision as the right thing to do.

“The pause is a prudent step to take, because when very serious adverse events occur that are also very rare, what matters most is ‘very serious,’” said John Moore, an immunologist at Weill Cornell Medicine. “Not only are individual members of the public at some risk, but so is the wider confidence in the Covid-19 vaccines.”

“It’s a reasonable but unproven assumption that the J&J and AstraZeneca vaccine safety concerns are linked by being related to an immune response against an adenovirus component,” he said. “So, FDA and scientists need time to better understand what is going on, which means a pause is the right course of action.”

But another expert acknowledged that the news may threaten the vaccine’s future use in this country.

“You have a greater chance of being in a car accident on the way to getting this vaccine than you have of having a problem from this vaccine. But that’s not how people view risk,” said Paul Offit, a vaccine expert at Philadelphia Children’s Hospital.

“In this country, you have two other vaccines, which are likely going to be produced in a quantity that enables everyone to be vaccinated,” he said. “So I think as we get more and more of the Moderna and Pfizer vaccine out there … I think it would not be surprising if … this vaccine would not come back onto the market.”

Offit was on the advisory panel that recommended the FDA authorize use of Johnson & Johnson’s vaccine.

The CDC and FDA said people who have received the Johnson & Johnson vaccine who develop certain symptoms within three weeks of receiving the vaccine should contact their health care provider. The symptoms were listed as severe headache, abdominal pain, leg pain, or shortness of breath.

The investigation into the Johnson & Johnson vaccine comes at a critical time for the Covid-19 vaccine rollout. Vaccine supplies that were scarce earlier in the year are starting to swell; rather than long lines, some jurisdictions are starting to report having unclaimed shots.

That had been expected. It has been known that behind the hordes desperate to be vaccinated was some significant portion of people who were worried about getting newly developed vaccines as well as some who will refuse vaccine under all circumstances. Persuading the former to get vaccinated in the face of a reports of a potential link between some of the Covid vaccines and a serious side effect will increase the challenge.

That said, vaccination with the AstraZeneca vaccine continues in many countries, though a number have placed limits on who can receive the vaccine — reserving its use for older adults, in whom these events have not been reported.

In Europe, where the AstraZeneca vaccine is being widely used, at least 222 suspected cases have been reported among 34 million people who have received the vaccine, according to a news report in the journal Science.

  • Interesting that it is 6 for 6 in pre menopausal women.

    Obviously a tiny dataset but so far VERY different to the AZ statistics which apparently show no meaningful sex skew after adjusting for the number of males and females who took it.

  • It is well recognized that a majority of the human population is immune to adenoviruses. Because of that, It is not wise to use adenovirus vectors to express the spike gene and use them as COVID vaccines. There are many varieties of adenoviruses. People in certain geographic regions tend to have immunity developed against certain strains of adenoviruses. So, it is not surprising that people react to it and develop adverse reactions in some locations but not others to the same vaccine. Sputnik V uses a strategy in which one type of adenovirus vector is used for the first vaccine and another strain is used for the second challenge. This could reduce some adverse reactions. I am wondering if blot clots or thrombocytopenia are reported for the Russian vaccine Sputnik V. Adenovirus vaccine design should be revised to overcome these problems.

  • Ms. Branswell,
    Thanks for an excellent, timely summary that answered a lot of pertinent questions not found by other writers.

  • So you’re pausing it to educate healthcare workers on how to treat thrombosis alongside thrombocytopenia? Err shouldn’t Doctors know how to treat this ALREADY as it is the same presentation, treatment and likely cause (autoimmune reaction against PF4) that occurs in HIT? You know the fairly COMMON reaction to Heparin???

    • This thrombocytopenia has a new name (to differentiate it from HIT) : VIPIT = Vaccine Induced Prothrombic Immune Thrombocytopenia. Injections of Low Molecular Weight Heparin (LMWH) = enoxaparin have proven to work (different angle on the complicated blood clotting processes). Doctors do know this, but CVST is a fairly fatal condition – hence the cautionary measure of halting and further investigation.

  • The piece of information that I’d like to see, but haven’t yet in any of the articles on this topic, is the rate of occurrence of this type of clot in the general population. How much more often are they happening in the vaccinated population?

    • Mr. Whiton;
      The reason that isn’t in my story is because the rate isn’t readily available. Peter Marks of FDA said this morning that CVST happens at a rate of between 2 to 14 per million people, in the setting of normal platelet counts. But that isn’t what’s seen here (and with the AstraZeneca vaccine). It’s a combination of CVST and low platelets — an unusual pattern for which they don’t really have a baseline rate.
      Best regards,
      Helen Branswell

  • I m wondering how to treat that adverse effect, how preventing it and the possible risk factors for it. A case control study my be helpful.

  • I think that pointing the finger at Johnson & Johnson might be slightly shortsided. My niece had the Moderna vaccine and she developed bloodclots. All the vaccines have had some negative affects on a limited number of people.

  • I think that ppinting the finget at Johnson & Johnson might be slightly shortsided. My niece had the Moderna vaccine and she developed bloodclots. All the vaccines have had some negative affects on a limited number of people.

  • I am an 61 year old woman with no medical health issues. I took the Johnson and Johnson vaccine about 3 weeks ago. Some side effects like sore arm, muscle aches, and restless sleeping but I am fine.

    • I had the J&J shot 11 days ago, had some purpora on right hand, also felt hormones were rather strange for my age 77.

  • I’m glad they paused this to assess the risk — and more importantly to determine a mitigation strategy for this side effect. But consider this statistic form a study at UCSD “Overall, 20 percent of the COVID-19 patients were found to have blood clots in the veins, and among patients in the intensive care unit, that statistic increased to 31 percent.” Presumably this is among hospitalized patients, but there are a lot of those — currently about 45,000 in the US. The treatment of blood clotting in COVID patients was one of the major advances last year that reduced mortality from COVID. I know that the manifestation of the blood clotting disorder differs somewhat between the vaccine and COVID, but I hope they can put in a “screen for risk, then monitor and treat” protocol for the side effects J&J vaccine.

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