By Brenda Goodman, MA, WebMD Health News
April 14, 2021 -- A CDC advisory committee is debating the safety of the Johnson & Johnson COVID-19 vaccine today after the CDC and FDA recommended that states hold off on using it after six women developed a rare but serious blood clot after getting the single-dose vaccine.
The clot occurred in the vessels that drain blood from the brain and the six patients also had a large drop in platelets, which increases the risk of bleeding.
This combination can lead to severe strokes that can lead to brain damage or death. Among the six cases, which came to light at the end of March and beginning of April, according to the CDC, one person died. They ranged in age from 18 to 48. More than 6.8 million doses of the Johnson & Johnson vaccine have been administered in the U.S.
According to a report to the Vaccine Adverse Event Reporting System (VAERS), which is maintained by the Department of Health and Human Services, the woman who died was 45. She developed a gradually worsening headache about a week after receiving the Johnson & Johnson vaccine.
On March 17, the day she went to the hospital, she was dry heaving. Her headache had suddenly gotten much worse, and the left side of her body was weak, which are signs of a stroke. A CT scan revealed both bleeding in her brain and a clot in her cortical vein. She died on March 18.
In addition to VAERS, which accepts reports from anyone, the CDC and FDA are monitoring at least eight other safety systems maintained by hospitals, research centers, long-term care facilities, and insurers, for signs of trouble with the vaccines. VAERS data is searchable and open to the public.
“These are very serious and potentially fatal problems occurring in a healthy young adult. It's serious and we need to get to the bottom of it,” said Ed Belongia, MD, director of the Center for Clinical Epidemiology and Population Health at the Marshfield Clinic Research Foundation in Marshfield, WI. Belongia leads a research team that helps the CDC monitor vaccine safety and effectiveness.
“Safety is always the highest priority, and I think what we've seen here in the past 24 hours is our vaccine safety monitoring system is working,” he said.
Others agree. "I think what CDC and FDA have detected is a rare, but likely real adverse event associated with this vaccine,” said Paul Offit, MD, director of vaccine education at Children’s Hospital of Philadelphia.
While much is still unknown about these events, they follow a similar pattern of blood clots reported with the AstraZeneca vaccine in Europe. That vaccine is now sold under the brand name Vaxzevria.
This has experts questioning whether all vaccines of this type may cause these rare clots.
“I think it’s likely a class effect,” said Offit, who was a member of the FDA advisory committee that reviewed clinical trial data on the J&J vaccine before it was authorized for use.
Adenovirus Vaccines Scrutinized
Both the Johnson & Johnson and AstraZeneca vaccines use the shell of another kind of virus — called an adenovirus to ferry genetic instructions for making the coronaviruses spike protein to our cells.
Adenoviruses are common, relatively simple viruses that normally cause mild cold or flu symptoms. The ones used in the vaccine are disabled so they can’t make us sick. They’re more like Trojan horses.
Once inside our cells, they release the DNA instructions they carry to make the spike protein of the new coronavirus. Our cells then crank out copies of the spike protein, which then get displayed on the outer surface of the cell membrane where they are recognized by the immune system.
The immune system then makes antibodies and other defenses against the spike so that when the real coronavirus comes along, our bodies are ready to fight the infection.
There’s no question the vaccine works. In clinical trials, the Johnson & Johnson vaccine was 66% percent effective against moderate to severe COVID-19 infection, and none of the patients who got COVID-19 after vaccination had to be admitted to the hospital or died.
The idea behind using adenoviruses in vaccines isn’t a new one. In a kind of fight-fire-with-fire approach, the idea it to use a virus, which is good at infecting us to fight a different kind of virus.
Researchers have been working on the concept for about 10 years, but the COVID-19 vaccines that use this technology are some of the first adenovirus vector vaccines deployed in humans.
Only one other adenovirus vaccine, for Ebola, has been approved for use in humans. It was approved in Europe last year. Before the Johnson & Johnson vaccine, no other adenovirus vector has been available for use in humans in the United States.
There are six adenovirus-vector vaccines for COVID-19. In addition to AstraZeneca and Johnson & Johnson, there’s the Russian-developed vaccine Sputnik V, along with Cansino from China, and the Covishield vaccine in India.
Adenovirus vaccines are more stable than the mRNA vaccines, such as the ones Pfizer and Moderna developed. That makes them easier to store and transport.
But they have a significant downside, too. Because adenoviruses infect humans out in the world, we already make antibodies against them. So there’s always a danger that our immune systems might recognize and react to the vaccine, rendering it ineffective. For that reason, scientists try to carefully select the adenovirus vectors, or carriers, they use.
The two vaccines under investigation for blood clots are slightly different. The Johnson & Johnson vaccine uses the vector AD26, because most of the population lacks pre-existing immunity to it. The AstraZeneca vaccine uses an adenovirus that infects chimpanzees, called ChAdOx1.
AstraZeneca’s vaccine has been widely used in the Europe and U.K., but has not yet been authorized in the US.
Last week, the European Medicines Agency, Europe’s counterpart to the FDA, ruled that unusual blood clots with low blood platelets should be listed as rare side effects on the AstraZeneca vaccine.
The decision came after reviewing 62 cases of cerebral venous sinus thrombosis (CVST) linked to the vaccine and 25 cases of another rare type of clot, called a splanchnic vein thrombosis. Splanchnic veins drain blood from the major organs in the digestive system, including the stomach, liver, and intestines. Eighteen of those events were fatal.
The reports were culled from reporting in Europe and the U.K., where around 25 million people have received the AstraZeneca vaccine, making these clots exceptionally rare, but serious.
So far, six cases of CVST have been reported in the US, after more than 6 million doses of the Johnson & Johnson vaccines have been administered.
A key question for U.S. regulators will be the background rate for these types of rare combinations of clots and deplenished platelets. The background rate is the number of events that would have been expected to have occurred naturally in a population of unvaccinated people.
On a press call on Tuesday, Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said somewhere between 2 to 14 cases per million people over the course of a year may develop one of these clots.
The first Johnson & Johnson doses were given in early March. That means the six cases came to light within the first few weeks of use of the vaccine in the US, a very short amount of time.
“These were six cases per million people for 2 weeks, which is the same thing as 25 million per year, so it’s clearly above the background rate,” Offit said.
Effect on Women Unclear
It’s also not clear why more cases seem to be in women than in men. Andrew Eisenberger, MD, an associate professor of hematology and oncology at Columbia University, said the most common causes of cerebral venous sinus thrombosis have to do with conditions that raise estrogen levels, like pregnancy and hormonal contraception.
“Estrogen naturally leads to changes in several clotting proteins in the blood that may predispose to abnormal blood clotting in a few different sites in the body,” he said. “The clotting changes we are encountering with some of COVID-19 vaccines are likely to be synergistic with the effects of estrogen on the blood.”
No matter the cause, the CDC on Tuesday alerted doctors to keep a high level of awareness for VIIT in patients who have received the Johnson & Johnson vaccination within the last 2 weeks. In those patients, the usual course of treatment with blood-thinning drugs like heparin may be harmful.
Symptoms to watch for include severe headache or backache, new neurologic symptoms, severe abdominal pain, shortness of breath, leg swelling, tiny red spots on the skin, or easy bruising.
Grappling With Evidence
On Wednesday, the CDC’s Advisory Committee on Immunization Practices, or ACIP, will meet in an emergency session to review the cases and see if any changes are needed to use the J&J vaccine in the US.
Last week, for example, the U.K. restricted the use of the AstraZeneca vaccine in people younger than age 30, saying the risks and benefits of vaccination are “more finely balanced” for this age group.
These are very serious and potentially fatal problems occurring in a healthy young adult. It's serious and we need to get to the bottom of it.
Ed Belongia, MD, director, Center for Clinical Epidemiology and Population Health at the Marshfield Clinic Research Foundation in Wisconsin.
With cases of COVID-19 rising again in the US, and the Johnson & Johnson vaccine currently the most convenient form of protection against the virus, the committee will have to weigh the risks of that infection against the risk of rare clots caused by vaccination.
They will also likely have to rule out whether any of the cases had COVID. At least one study has reported CVST clots in three patients with confirmed COVID infections. In Europe, COVID infection did not seem to play a role in the formation of the clots with low platelets.
Hilda Bastian, a clinical trials expert who co-founded the Cochrane Collaboration, said it won’t be an easy task. Much will depend on how certain they feel that they know about all the events linked to the vaccine.
“That’s the really, really hard issue from my point of view for them right this moment. Have we missed any? Or how many are we likely to have missed?” said Bastian, who lives in Australia.
“In a country that size with that fragmented healthcare system, how sure can you be that you know them all? That’s going to be a really difficult situation for them to grapple with, the quality of information that they’ve got,” she said.