As Covid-19 vaccines are rolled out across the world, a growing band of recipients are complaining of being flattened by side effects, especially after a second dose. Recipients describe symptoms from fever to fatigue that are more profound than the jolt some get from a seasonal flu shot. Although the post-vaccination malaise is generally innocuous and fades after a day or two, some hospitals and medical centers are staggering immunizations of health workers to avoid a brief cluster of absenteeism.

1. What reactions can occur?

Typical symptoms include a sore arm, usually localized to the area the inoculation was given, and systemic symptoms, such as a mild fever or elevated temperature, headache and muscle aches. Some studies have found that younger adults report localized and systemic reactions more frequently than people over 65 years old. A type of skin eruption, known as a morbilliform rash, was described in a 30-year-old male health-care worker two days after his second jab. The rash, which covered most of his back, resolved on its own after a day.

2. Are they cause for concern?

Reactions may be unpleasant, but they are usually short-lived and far less serious than what’s inflicted by a natural infection. Vaccines are extensively tested for safety before they are released. Once they are in large-scale use, they are rigorously monitored in “post-marketing” surveillance systems for unexpected or rare reactions that are too uncommon to have been picked up in clinical trials. While adverse reactions to a vaccine aren’t uncommon, these products wouldn’t be licensed if they were likely to be severe or long-lasting.

3. What causes reactions to vaccines?

Vaccines are designed to mimic a natural infection without the full-blown disease, thus generating a protective immunity. Reactions usually result from the immune system’s response to the key component: an antigen that resembles whatever bug it’s designed to fight. Normally, when the body encounters a bacteria, virus or some other potential foe, immune defenses seek to neutralize and destroy it. Chemicals that attract cells to kill the invader are released in a process that can raise the body temperature, said Peter English, a consultant in communicable disease control in the U.K. and a former editor of Vaccines in Practice magazine. A vast army of so-called T cells and B cells are recruited to generate lasting “memory” of the foe and how to thwart it. “In learning to recognize the pathogen, the body goes through the same immune reactions as it would if it had met the pathogen for real, producing many of the same reactions,” English said.

4. What else can cause a reaction?

Vaccines may also contain components that can induce a reaction, or enhance the immune response to the vaccine antigens, English said. Covid-19 vaccines may also include:

• Preservatives to prevent the vaccine from spoiling.

• Microscopic bubbles of lipids or fatty materials that contain the genetic material for mRNA vaccines (manufactured by Moderna Inc., Pfizer Inc. and BioNTech SE) to instruct cells to produce SARS-CoV-2 antigens.

• Harmless viruses to smuggle genetic material into the cells to instruct them to produce SARS-CoV-2 antigens.

• Harmless chemical “adjuvants” designed to increase the immune response to the antigens.

5. Why are reactions to the second dose worse?

It takes some time for the immune system to hone its response to a new pathogen. Immune memory cells are programmed such that when they encounter an invader a second time -- either from a natural infection or vaccine antigens -- they are primed to respond faster and more vigorously. That recognition typically triggers mass-production of immune-signaling molecules or “cytokines” that are responsible for the muscle aches, fevers, chills and fatigue recipients sometimes feel. The upside is that the second encounter acts as a booster that should result in a more robust, longer-lasting immune response.

The following data represent self-reported symptoms experienced within the first week of each dose among 3.6 million recipients of either the Pfizer-BioNTech or Moderna vaccine as reported April 5 by the CDC Covid-19 Response team in JAMA Insights journal.

6. What’s the reaction like for Covid-19 survivors?

Their reaction to the shot may be more pronounced, but the benefits are likely to be so as well. Florian Krammer and colleagues at the Icahn School of Medicine at Mount Sinai in New York compared the effects of mRNA vaccines on people with and without pre-existing antibodies to the coronavirus. The researchers found antibody levels of those with preexisting immunity were 10 to 45 times as high as those without at the same points in time after the first vaccine dose. Localized reactions at injection site to the vaccine occurred with equal frequency in both groups at the time of vaccination and resolved spontaneously days later. However, systemic side effects occurred after vaccination in 89% of those with preexisting immunity, compared with 46% of vaccinees without any.

7. Is feeling lousy after vaccination a good sign?

It’s reassuring to think that’s the case -- and it might be, English said, although “I’m not sure that there’s a wealth of data confirming it.” At the very least, a mild, short-lived fever signals that the immune system is responding in a way that should confer protection against the coronavirus if it’s encountered for real.

8. Can you take something for it?

A slight fever below about 38.5 degrees Celsius (101 degrees Fahrenheit) is part of the body’s normal response to infection and isn’t harmful. If it can be tolerated, rest and fluids are the ideal remedy, according to English. A sustained temperature above 39 degrees Celsius is more serious, especially in infants. Taking aspirin, acetaminophen/paracetamol (such as Tylenol), or a non-steroidal anti-inflammatory drug such as ibuprofen to relieve pain and fever isn’t likely to impair the quality of the immune response.

(Adds table in section 5.)

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