/U.S. Seeks to Pause J&J Covid-19 Vaccine Use Amid Clotting Reports

U.S. Seeks to Pause J&J Covid-19 Vaccine Use Amid Clotting Reports

U.S. health authorities recommended a pause in the use of Johnson & Johnson’s Covid-19 vaccine in order to investigate rare but severe cases of blood clots, a setback to vaccination efforts racing against virus variants.

The U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention announced the move Tuesday, after finding that six women between the ages of 18 and 48 years who got the vaccine had developed blood clots and one died.

The severe side effects were rare—more than 6.8 million doses of J&J’s shot have been administered in the U.S.—but health authorities said they moved quickly out of an abundance of caution.

“The fact that a pause was done, I think, is just a testament to how seriously we take safety,” said Anthony Fauci, the government’s top infectious-disease official.

The action prompted the U.S. government to suspend at its vaccination sites administration of J&J’s vaccine, a federal health official said, while some states and other authorities moved to administer other authorized shots. Some countries, meanwhile, also moved quickly to limit the shot’s use.

The U.S. government’s review may only take a few days, health authorities said. A panel of outside experts will meet Wednesday to review the matter for the CDC, while Acting FDA Commissioner Janet Woodcock indicated the agency will be able to quickly conduct its review.

At the same time, the halt comes at a dangerous time during the more than year-old pandemic, as health authorities race to vaccinate as many people as possible before variants develop that can evade the shots.

​Europe’s top drug regulator endorsed AstraZeneca’s vaccine after it was suspended in several countries over blood-clot concerns. WSJ explains what’s at stake for a shot that’s been widely used around the world and may soon be considered for emergency use in the U.S. Photo: Mykola Tys/SOPA Images

Among the biggest hurdles is overcoming hesitancy to get vaccinated, and the specter of blood clots could add to concerns about the safety of the shots. A pause in the use of the J&J vaccine could also be felt especially in areas that lacked the special freezers required to store the two-dose shots from Pfizer Inc. and its partner BioNTech SE and from Moderna Inc. Places like college campuses that have potentially transient populations have preferred the single-dose J&J vaccine.

Yet the impact could be limited, especially if J&J vaccinations are allowed to resume. The Pfizer-BioNTech and Moderna vaccines have proved relatively safe so far, and those companies have been ramping up production as they gained more experience making the shots and expanded their manufacturing capabilities.

J&J’s vaccine wasn’t a big source of doses yet. Federal officials expected to allocate about 26.5 million doses of the Pfizer-BioNTech and Moderna vaccines combined this week, compared with 1.5 million of J&J’s.

Combined, the three companies have delivered 245.4 million doses, and 192.3 million of these have been administered to people, according to the CDC.

President Biden played down the significance of the pause, saying the 600 million doses his administration had helped secure of the Pfizer-BioNTech and Moderna vaccines would be sufficient to cover the eligible U.S. adult population.

“There is enough vaccine—that is basically 100% unquestionable—for every single, solitary American,” Mr. Biden told reporters Tuesday.

President Biden’s Covid-19 coordinator, Jeff Zients, said the administration was working with state and federal partners to get people who were scheduled to receive the J&J shot signed up for a Pfizer or Moderna vaccine.

Pfizer Chief Executive

Albert Bourla

said the company upped production of its Covid-19 vaccine and will be able to deliver 10% more doses to the U.S. by the end of May than previously agreed. In addition, Mr. Bourla said on Twitter, Pfizer will supply the full 300 million doses agreed on for the end of July two weeks early.

J&J said it knows that a small number of people who got its vaccine developed blood clots and had low levels of blood platelets. J&J said it is working with health authorities and medical experts.

The company also said it has decided to delay the rollout of its vaccine in Europe.

J&J has paused vaccinations in all ongoing clinical trials of its vaccine while it updates guidance for research investigators and study subjects. J&J had been conducting a trial testing two doses of its vaccine in adults, as well as a study in adolescents ages 12 to 17 years old.

Clots can be life-threatening, even fatal, if they choke off blood and therefore oxygen flow to the brain or heart. The type of blood clot seen in some people receiving the J&J vaccine was called a cerebral venous sinus thrombosis, which can prevent blood from draining out of the brain and can lead to a hemorrhage.

In the case of J&J’s shot, six women ages 18 to 48 developed blood clots after taking the J&J vaccine, the FDA and CDC said. The clots developed six to 13 days after vaccination. The women also had in their blood low counts of platelets, which help with clotting.

Given the nature of the side effect, doctors shouldn’t use the normal course of clotting treatment, involving a drug called heparin, the FDA and CDC said. “In this setting, administration of heparin may be dangerous, and alternative treatments need to be given,” they said.

J&J’s Covid-19 vaccine was the third authorized for use in the U.S.



Photo:

Tom Williams/CQ Roll Call/Zuma Press

The agencies said people vaccinated with J&J’s vaccine should notify their doctor if they develop severe headache, abdominal pain, leg pain, or shortness of breath within three weeks after vaccination.

European health authorities have also seen dangerous clots emerge in a relatively small number of people taking a Covid-19 vaccine developed by AstraZeneca PLC and the University of Oxford. That vaccine has been available in the U.K. and in Europe, but isn’t authorized for use in the U.S.

Earlier this month, U.K. health authorities recommended against giving AstraZeneca’s shot to people under 30 years after receiving reports of rare but deadly blood clots. Countries including Canada and Germany have also restricted use.

A link between the AstraZeneca vaccine and the clotting incidents is unclear. Scientists in Germany and Norway said the vaccine may cause an autoimmune reaction that leads to clots in the brain.

U.S. Covid-19 vaccines administered by type

It is possible the clotting is related to the gene- and viral-based technology behind the J&J and AstraZeneca shots.

Both viral-vector vaccines contain a virus that causes the common cold, but which has been rendered harmless. That virus is engineered to include genetic instructions that set off an immune response to protect people against the coronavirus.

The Pfizer and Moderna vaccines use a different technology, called messenger RNA, to achieve the same goal.

The risk of these rare types of blood clots is likely to be a “class effect” of viral-vector vaccines, said Dr. Paul Offit, director of the vaccine education center at Children’s Hospital of Philadelphia. He said it is possible they are causing immune-system antibodies against a protein, a process that can lead to clots.

Dr. Peter Marks, the FDA’s top vaccine official, said officials haven’t determined a definitive cause, but the vaccine may be causing a rare immune response affecting blood platelets.

Number of vaccine doses procured, selected countries/entities

The type of brain clots seen in the vaccine recipients normally only occur in between two and 14 per million people, Dr. Marks said. But seeing such clots along with low platelet levels “create a pattern” similar to that in Europe with AstraZeneca’s vaccine, he said.

U.S. health authorities said there don’t appear to be similar issues with the other authorized vaccines. Dr. Marks said there have been over 180 million doses of the Moderna or Pfizer vaccines administered, and that such events haven’t been reported with those shots.

Health authorities have been trying to vaccinate as many people as possible to stay ahead of any coronavirus strains able to elude the shots.

Now is an especially fraught moment in the vaccination push, health experts say, because it pressures the virus to mutate before communitywide immunity develops.

“What we’re in right now is this race of can we get everyone immunized so we stop transmitting…and can we do it fast enough to stop these variants,” said Lisa Lee, an infectious-disease epidemiologist and associate vice president at Virginia Polytechnic and State University.

To accelerate vaccinations, health authorities have been seeking to overcome hesitancy about getting the shots. Support for getting vaccinated has risen as shots rolled out, though surveys have found around one in five respondents were hesitant or unwilling to get vaccinated.

Health officials have been seeking to overcome the concerns, especially as supplies increased, to achieve the herd immunity required for the lifting of pandemic restrictions and full reopening of schools, businesses an other establishments.

J&J’s vaccine was the third authorized for use in the U.S., after it was shown to be 66% effective in preventing Covid-19 disease in a large study.

How Viral Vector Vaccines Work

Johnson & Johnson and AstraZeneca’s vaccines rely on a different mechanism for conferring immunity than traditional vaccines.

Traditional Vaccines

1. In classic vaccines, such as those against measles and polio, the patient is inoculated with weakened or inactivated versions of the virus. This triggers the immune system to produce specialized antibodies that are adapted to recognize the virus

2. After vaccination, the antibodies remain in the body. If the patient later becomes infected with the actual virus, the antibodies can identify and help neutralize it.

Scientists have isolated genes in the new coronavirus responsible for producing these spike proteins. The genes are spliced into weakened, harmless versions of other viruses.

Instead of using the whole virus to generate an immune response, the vaccine relies on coronavirus’s outer spike proteins, which are what antibodies use to recognize the virus.

Weakened virus with

spike protein genes

When injected into a patient, the genetically engineered viruses enter healthy cells where they produce coronavirus spike proteins.

Once exported from the cells, the spike proteins prompt the immune system to mount a defense, just as with traditional vaccines.

Vaccine-generated antibody response

1. In classic vaccines, such as those against measles and polio, the patient is inoculated with weakened or inactivated versions of the virus. This triggers the immune system to produce specialized antibodies that are adapted to recognize the virus

2. After vaccination, the antibodies remain in the body. If the patient later becomes infected with the actual virus, the antibodies can identify and help neutralize it.

Scientists have isolated genes in the new coronavirus responsible for producing these spike proteins. The genes are spliced into weakened, harmless versions of other viruses.

Instead of using the whole virus to generate an immune response, the vaccine relies on coronavirus’s outer spike proteins, which are what antibodies use to recognize the virus.

Weakened virus with

spike protein genes

When injected into a patient, the genetically engineered viruses enter healthy cells where they produce coronavirus spike proteins.

Once exported from the cells, the spike proteins prompt the immune system to mount a defense, just as with traditional vaccines.

Vaccine-generated antibody response

1. In classic vaccines, such as those against measles and polio, the patient is inoculated with weakened or inactivated versions of the virus. This triggers the immune system to produce specialized antibodies that are adapted to recognize the virus

2. After vaccination, the antibodies remain in the body. If the patient later becomes infected with the actual virus, the antibodies can identify and help neutralize it.

Scientists have isolated genes in the new coronavirus responsible for producing these spike proteins. The genes are spliced into weakened, harmless versions of other viruses.

Instead of using the whole virus to generate an immune response, the vaccine relies on coronavirus’s outer spike proteins, which are what antibodies use to recognize the virus.

Weakened virus with

spike protein genes

When injected into a patient, the genetically engineered viruses enter healthy cells where they produce coronavirus spike proteins.

Once exported from the cells, the spike proteins prompt the immune system to mount a defense, just as with traditional vaccines.

Vaccine-generated antibody response

1. In classic vaccines, such as those against measles and polio, the patient is inoculated with weakened or inactivated versions of the virus. This triggers the immune system to produce specialized antibodies that are adapted to recognize the virus

2. After vaccination, the antibodies remain in the body. If the patient later becomes infected with the actual virus, the antibodies can identify and help neutralize it.

Instead of using the whole virus to generate an immune response, the vaccine relies on coronavirus’s outer spike proteins, which are what antibodies use to recognize the virus.

Scientists have isolated genes in the new coronavirus responsible for producing these

spike proteins. The genes are spliced into weakened, harmless versions of other viruses.

Weakened virus with

spike protein genes

When injected into a patient, the genetically engineered viruses enter healthy cells where they produce coronavirus spike proteins.

Once exported from the cells, the spike proteins prompt the immune system to mount a defense, just as with traditional vaccines.

Vaccine-generated antibody response

Health authorities looked forward to its launch, because it required just one dose and was easier to store and administer than the two-dose shots from Pfizer-BioNTech and Moderna that have to be kept at ultracold temperatures or can only be refrigerated for a shorter duration than J&J’s.

Some states and vaccine providers quickly made alternative plans in response to the call for a pause by federal health officials.

New York Gov. Andrew Cuomo tweeted that state-run mass vaccination clinics would offer the Pfizer-BioNTech vaccine in lieu of the J&J vaccine to people with appointments Tuesday. Likewise, city-run sites in Los Angeles shifted 3,000 vaccinations scheduled for Tuesday to Pfizer’s shot from J&J’s, Mayor Eric Garcetti said.

Walgreens Boots Alliance Inc.

said it immediately suspended administration of J&J’s vaccine at its retail pharmacies and off-site clinics and will await further guidance. The company is reaching out to people who had appointments to reschedule them.

Separately, Australian health officials said Tuesday the country has decided against using J&J’s shot, after a panel of scientific experts advising the government said it shouldn’t buy any more vaccines of its type.

South Africa’s health minister said the country would temporarily halt its rollout of Johnson & Johnson’s Covid-19 vaccine.

Johnson & Johnson’s vaccine has been expected to account for more than 15% of the European Union’s second-quarter deliveries, or 55 million of 360 million expected doses, during the three months from March through June. European health authorities have been looking into the clotting issue. Deliveries of J&J shots to the continent began Monday.

The EU’s European Medicines Agency, which has closely analyzed concerns about blood clots among recipients of the AstraZeneca vaccine, is also studying clot concerns about the J&J vaccine.

Certain types of blood clots were seen in a small number of subjects in the large clinical trial of J&J’s vaccine that supported its authorization in late February. The FDA said there wasn’t enough evidence at the time to determine whether the vaccine was causing the clots, but said it would monitor the situation.

J&J paused the large study of its vaccine in October because one vaccine recipient had a type of blood clot called a transverse sinus thrombosis resulting in a brain hemorrhage, according to an FDA document. J&J investigated and found that it wasn’t related to the vaccine, and resumed the study.

J&J also has had problems manufacturing its vaccine. A batch of the vaccine’s main ingredient that was being made at a contractor’s plant in Baltimore was recently ruined by contamination, and no doses were distributed from the batch. Health regulators still haven’t authorized the plant where the mishap occurred, hurting J&J’s ability to churn out more doses.

Mass vaccination clinics administering the J&J vaccine in North Carolina, Colorado and Georgia have closed temporarily in recent weeks after some people receiving the shot experienced adverse effects. It wasn’t immediately clear whether the vaccine caused them.

Write to Peter Loftus at peter.loftus@wsj.com and Thomas M. Burton at tom.burton@wsj.com

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