How Safe Are Covid Vaccines? Here’s the Rundown on Reactions

(Bloomberg) -- Covid vaccines are designed to prevent a disease that has so far killed more than 5 million people worldwide. No pharmaceutical, however, is completely benign. The goal is to ensure the benefits outweigh the risks. So far, the vaccines have been connected to a relatively small number of cases of heart inflammation, blood clots, a rare immune-system disorder, and a serious -- but treatable -- allergic reaction called anaphylaxis. A concern that vaccinations could be linked to temporary facial paralysis has not been confirmed.

1. What happened with the cases of heart inflammation?

Cases of myocarditis, inflammation of the heart muscle, have been reported in people, especially male adolescents and young adults, who received vaccines developed by the Pfizer Inc.-BioNTech SE partnership and Moderna Inc. These shots use an innovative technology called messenger RNA that temporarily turns the body’s cells into tiny vaccine-making factories. A study published in October put the risk of the reaction at 0.8 cases per 1 million after a first dose and 5.8 cases per 1 million after a second one. The U.S. Centers for Disease Control and Prevention said most people recover fully but that potential long-term effects were unknown. A number of European countries have advised that younger people not receive the Moderna vaccine; so-far unpublished data from Nordic countries suggest the side effect is more common with that formulation than with Pfizer-BioNTech’s.

2. What about the blood clots?

Very rare reports of an unusual clotting syndrome have been associated especially with vaccines from Johnson & Johnson and AstraZeneca Plc that use similar technologies, although some cases have been seen after the shot from Pfizer-BioNTech. The syndrome, seen more often in young people, is atypical because it occurs alongside low levels of blood platelets -- the key element in formation of blood clots. Several countries, mainly in Europe, early this year briefly suspended use of the AstraZeneca vaccine or restricted its administration to younger people. U.K. health authorities advised that those younger than 30 be offered an alternative vaccine, if available. In the U.S., health officials paused use of the J&J vaccine to assess the side effect and raise doctors’ awareness of how to recognize and treat it. Use of the vaccine resumed in April, and it was subsequently authorized in numerous countries.

3. What’s the risk?

Regulators in the U.K. put the overall risk of the clots at about 4 in a million people who receive the AstraZeneca vaccine. U.S. officials reported seeing 3 cases per million people who received the J&J shot and said women ages 18 through 49 were at highest risk. The U.K., as of Oct. 27 reported 424 cases, 72 of which were fatal, following vaccination with the AstraZeneca shot, and 22 cases, including two fatalities, following use of the Pfizer-BioNTech vaccine. In the U.S., there were five deaths through Nov. 10; Australia had reported eight as of Nov. 4, and Norway reported four as of Oct. 26.

4. What are signs to watch for?

People who have received the shots two to four weeks earlier should watch for symptoms that may prefigure the onset of clotting. These include shortness of breath, chest pain, leg swelling, persistent belly pain, severe headaches, blurred vision and tiny blood spots under the skin beyond the vaccine injection site.

5. What’s causing the clots?

U.K. health officials described the syndrome as similar to a rare side effect of treatment with heparin, an anticoagulant, in which the body forms antibodies against platelets. How or why the vaccine might be involved in such a process is still under investigation. Researchers are looking at whether the side effect is related to a harmless version of an adenovirus, a cold virus, that’s included in both the J&J and AstraZeneca shots, although that wouldn’t explain the cases after use of the Pfizer-BioNTech shot. The adenovirus delivers a gene that instructs cells to make the spike protein that gives the coronavirus that causes Covid its crown-like appearance. This, in turn, stimulates the body to mount immune responses to the virus, so that it is primed for a fight if it ever encounters the real thing. Russia’s Sputnik V vaccine and another from China’s CanSino Biologics also use an adenovirus platform.

6. What about the allergic reactions?

The body fights foreign invaders through a variety of mechanisms that include making protective proteins called antibodies, releasing toxins that kill microbes, and marshaling guardian cells to battle the infection. As in any conflict, sometimes the effort to repel an infection can itself be damaging. In rare cases, it can produce runaway inflammation and swelling of tissues in a serious allergic reaction called anaphylaxis. As much as 5% of the U.S. population has had such a reaction in response to something, including drugs, foods and insect stings. It can be fatal if, for example, the person’s airway swells shut, though deaths are rare.

7. How often have Covid vaccines triggered cases?

In the U.S., according to the Centers for Disease Control and Prevention, it occurs in just 2 to 5 people for every million receiving a Covid vaccine. The risk of contracting Covid outweighs that posed by the vaccines, officials and clinicians say. Anaphylaxis is a known risk of vaccination. Such reactions occur about 1.3 times per million doses of flu vaccine administered. With other vaccines they have been seen at rates of 12 to 25 per million doses, though the studies were small. When anaphylaxis occurs, it is almost always within half an hour of administering the vaccine, according to the CDC.

8. What’s being done to manage the risk?

The U.K. and U.S. have advised people who have allergies to any component of a Covid vaccine not to receive it. Anaphylaxis can be quickly countered with antihistamines in tandem with adrenaline injectors like Mylan NV’s Epi-Pen that slow or halt immune reactions, and health workers giving the vaccine are keeping such items at the ready. These treatments don’t cancel out the beneficial effects of vaccines. In the U.S., health workers are observing everyone who receives the vaccine for at least 15 minutes post-injection to watch for signs of a reaction; those with a worrying history of allergic reaction are monitored for twice as long. People who have had reactions to a first dose of vaccine shouldn’t receive a second, according to the CDC.

9. Do we know what in the shots is causing anaphylactic reactions?

That isn’t clear. Two leading candidates are polyethylene glycol -- a chemical found in many foods, cosmetics and medications -- and lipid nanoparticles that encapsulate the messenger RNA in the Moderna and Pfizer-BioNTech vaccines, according to Eric Topol, a clinical trials expert and director of the Scripps Research Translational Institute. Polyethylene glycol has been previously linked to a handful of anaphylaxis cases. Once a cause has been narrowed down, it may be possible to make Covid vaccines even safer than they are now, Topol said.

10. What about the immune system disorder?

The fact sheet for J&J’s vaccine was revised in July to warn of the risk of Guillain-Barré Syndrome, a rare condition in which the immune system attacks the nerves, after reports of 100 cases. The CDC said they were seen mostly in men over the age of 50 about two weeks after being immunized. The U.S. Food and Drug Administration said between 3,000 and 6,000 people a year develop the disorder, which can result in muscle weakness or paralysis, and most people fully recover from it.

11. And temporary facial paralysis?

In studies testing the Moderna and Pfizer-BioNTech inoculations, more people developed Bell’s palsy, an episode of muscle weakness or paralysis that typically affects just one side of the face, after receiving vaccine doses than placebo shots. The imbalance turned out not to be substantiated, however, based on the massive safety database the CDC has collected on millions of people vaccinated since the drugs were authorized for the general public. Also, the drugs regulator in the U.K., where the Pfizer-BioNTech formulation is in use, noted that as of Oct. 27, the number of reports of Bell’s palsy among those vaccinated does not suggest an increased risk.

12. What’s known about other deaths after vaccinations?

With roughly 31 million Covid shots administered each day, it’s inevitable that some people will die soon after they receive immunizations; the question is, did the vaccine cause it? Determining that can be very difficult, particularly in cases where the deceased had one or more underlying illness, was aged, frail or all three. In the U.S. and the U.K., apart from fatalities from the clotting syndrome, authorities have reported that the evidence does not suggest that vaccines played a role in post-vaccination deaths. In Norway, an expert group of geriatric specialists studied the first 100 deaths among nursing home residents following receipt of the Pfizer-BioNTech vaccine and concluded that a causal link to the inoculation was “likely,” though not certain, in ten cases. The group recommended that in cases where life expectancy is short, the risks and benefits of vaccination should be carefully assessed. It suggested that the risk of death from vaccine reactions could be reduced using measures such as good hydration.

13. Have other new vaccines had safety issues?

Before regulatory authorities authorize a new vaccine, it must be tested both for safety and efficacy in thousands of human volunteers. Still, there have been cases where safety issues have arisen after authorization. European regulators in 2011 recommended restricting the use of a new swine-flu vaccine from GlaxoSmithKline Plc after it was linked to rare cases of narcolepsy. A vaccine against Lyme disease developed by the same company, then called SmithKline Beecham, was pulled in 2002 amid concerns about links to arthritis. Some vaccines have been shown to do the opposite of what they’re designed to do by inducing unwanted immune responses. In recent years, Sanofi’s vaccine against dengue, which a person can get multiple times, was found to cause more severe disease in those who become infected for the first time after getting the inoculation. Documented reports of unexpected side effects from novel vaccines are different from the persistent and incorrect belief that well-established vaccines against childhood diseases carry significant risks.

The Reference Shelf

• Related QuickTakes on Covid treatments, the U.S. vaccine mandate and mRNA vaccines.
• The CDC’s morbidity and mortality weekly reports.
• Researchers take a deep dive into safety issues in the journal Vaccines.
• Follow the inoculation rollout using Bloomberg’s Vaccine Tracker.

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