Like all new drugs, the vaccines that have been authorized to protect against Covid-19 come with some safety concerns and side effects. Many people who’ve received the first two Western shots deployed, one from Pfizer Inc. and BioNTech SE, and another from Moderna Inc., have experienced fever, headache and pain at the site of the injection. These side effects generally disappear quickly. More worrisome, Norway has reported deaths among elderly people with serious underlying health conditions following administration of the Pfizer-BioNTech vaccine -- possibly linked to those side effects. A few other recipients of the various jabs have had a serious, but treatable, allergic reaction, called anaphylaxis.

1. What’s known about the deaths?

Thirty-three were reported in mid-January among some 42,000 people given the Pfizer-BioNTech vaccine in Norway, where authorities have prioritized the immunization of nursing-home residents. Those who died were all in the “75 years +” bracket (exact ages weren’t given for privacy reasons) and included terminally ill patients anticipated to have only weeks or months to live. All deaths occurring within a few days of vaccination are carefully assessed. Health authorities in Norway say there’s no evidence of a direct link between the 33 cases and the vaccine they received. An average of 400 people die each week in nursing homes and long-term care facilities, according to the Norwegian Medicines Agency. Sigurd Hortemo, the agency’s chief physician, said he can’t rule out that common adverse reactions to the vaccine, such as fever and nausea, may be potentially life-threatening in patients with severe underlying health problems.

2. Have there been deaths elsewhere?

In Germany, where more than 800,000 people have received their first of two doses of the the Pfizer-BioNTech vaccine, the Paul Ehrlich Institute has investigated at least seven cases of elderly people dying shortly after vaccination. In its report, it said the deaths were probably due to the patients’ underlying diseases including carcinomas, kidney deficiencies and Alzheimer’s, not the inoculation.

3. What reactions did these fatal cases develop?

The deaths in Norway were associated with fever, nausea and diarrhea -- relatively common, short-lived effects that some people can experience after almost any vaccination, according to information relayed by Australia’s Therapeutics Administration. (It’s working with the European Medicines Agency, which includes Norway, before deciding whether to approve the drug in Australia.) The reactions aren’t expected to be of significance in the vast majority of people. Millions of doses of the Pfizer-BioNTech vaccine have been administered in the U.S., U.K. and some other countries with no deaths reported due to the vaccine, Abrar Chughtai, a lecturer in the School of Public Health and Community Medicine at the University of New South Wales, told the Australian Science Media Centre.

4. What is known about the vaccine’s risks in older, frail people?

Not a great deal. It’s possible that common adverse reactions to vaccines that aren’t dangerous in fitter, younger patients may aggravate underlying disease in the elderly, Steinar Madsen, the Norwegian agency’s medical director, told The BMJ medical journal. Only a limited number of people older than 85 years participated in large clinical trials of the Pfizer-BioNTech vaccine, the agency said. The average trial participant for the two approved Western vaccines was in his or her early 50s.

5. What is being done in response to the deaths?

The Norwegian Institute of Public Health has updated its Covid-19 vaccination guide with more detailed advice on vaccinating the elderly who are frail. “We are now asking for doctors to continue with the vaccination, but to carry out extra evaluation of very sick people whose underlying condition might be aggravated by it,” Madsen said. The evaluation includes discussing the risks and benefits of vaccination with patients and their families to decide whether or not immunization is prudent. Separately, Nordic neighbor Finland has recommended against systematic vaccinations of terminally ill patients whose active treatment (in other words, those being palliated) has been stopped. The reason is that common side-effects such as temporary fever can weaken their condition.

6. What other serious reactions have there been?

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 to various substances. It can be fatal if, for example, the person’s airway swells shut, though deaths are rare. Allergies to insect stings and foods can provoke it, though drug reactions are the most common cause of anaphylaxis fatalities in the U.S. and U.K.

7. Where have Covid-19 vaccines triggered cases?

According to a Jan. 6 report by the U.S. Centers for Disease Control and Prevention, 21 cases of anaphylaxis associated with the Pfizer-BioNTech vaccine had been confirmed in the country as of Dec. 23. Of those people, 17 had a documented history of allergies, and seven had a history of anaphylaxis. A Dec. 19 presentation from the CDC referenced two cases in the U.K. associated with the same vaccine, and later in the month, in Israel, a man suffered anaphylactic shock an hour after receiving it, according to the Jerusalem Post. He said he’d had earlier reactions to penicillin, the paper reported. CDC officials say they’ve also seen the reactions in recipients of the Moderna shot and are compiling data on them.

8. Has anaphylaxis been connected to vaccines before?

Yes. 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. For the Pfizer-BioNTech Covid vaccine, according to the CDC, the rate as of Dec. 23 is 11.1 per million doses, which is very low. The agency said the risk surrounding the vaccine is less than the risk of getting a severe case of Covid-19.

9. How long does the risk of allergic reaction last?

Usually not long. Anaphylactic reactions normally occur within minutes to hours of exposure to a specific substance, said Michael Kinch, a drug development expert and associate vice chancellor at Washington University in St. Louis. In the U.S. so far, the time lag ranged from two to 150 minutes, with the median being 13 minutes, according to the CDC.

10. What’s being done about that?

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.

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

That isn’t clear. The two leading candidates are polyethylene glycol -- a chemical found in many foods, cosmetics and medications -- and lipid nanoparticles that encapsulate the messenger RNA, a genetic component in the 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.

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