COVID-19 infection vs. vaccination: Which is better for immunity?

Both a natural COVID-19 infection and a vaccination are expected to protect you from getting sick with COVID in the future. But how are they different? What are the pros and cons of each? And is one better for immunity?

Here’s a look at why medical experts think vaccination is safer and better protection than natural infection for most people — and why health officials recommend getting the vaccine even if you think you’ve had COVID-19.

How does COVID-19 make you sick — and how do vaccines prevent that?

SARS-CoV-2, the coronavirus that causes COVID-19, infects and sickens people by attaching to and entering cells using a protein on its outer surface called the spike protein.

The goal of vaccination is to teach specialized immune cells called T cells and B cells what the spike protein looks like, so they can recognize it quickly and prevent infection and illness in the first place. This is the kind of immune learning that also happens during a natural infection.

“We can target it and kind of block this binding of the spike protein on the virus to our cells,” said Prof. Alyson Kelvin of Dalhousie University in Halifax and the Canadian Centre for Vaccinology at Vido-Intervac in Saskatoon. 

Kelvin studies how people develop illness after infection with SARS-CoV-2 and also how to measure the immune response to vaccines.

Vaccines mimic certain aspects of a natural infection without exposing someone to a disease-causing virus that can replicate in your body. Most COVID-19 vaccines find different ways to expose people to just the spike protein. (For example, mRNA vaccines like the Pfizer and Moderna vaccines give your cells instructions to make the spike protein in your body.)

“The vaccine trains your immune system to respond to the virus without any disease effects,” Kelvin said.

How do you develop immunity to COVID-19 from a natural infection?

When your body is exposed to a pathogen it has never seen before, it activates a part of your defences called the innate immune system, which recognizes patterns associated with viruses and viral infection. 

That sets off messenger proteins called cytokines that generate two kinds of immune response: 

  • Inflammation, which helps activate the immune system, calling in immune cells to attack both the virus itself and infected cells. However, too much inflammation can damage tissues. 
  • Anti-viral. For example, special cytokines called interferons disrupt viral replication.

Once the innate immune system is activated, immune cells called dendritic cells carry viruses or pieces of viruses to the lymph nodes, where the adaptive immune system is activated. 

That’s the part of the immune system that learns to target specific pathogens and deal with them quickly the next time they’re spotted. Dendritic cells link the innate and adaptive immune systems. They carry viruses to the lymph nodes and show parts of the virus to specialized cells called T-cells, teaching them to recognize it.

Helper T-cells activate:

  • B-cells, which generate antibodies that bind to and deactivate the spike protein. 
  • Cytotoxic T-cells, which kill infected cells.

Which is safer, COVID-19 vaccination or infection? 

The data is clear: vaccination.

Serious side-effects from both clinical trials and widespread vaccination for COVID-19 have been very rare, and even those that have appeared, such as occasional severe allergic reactions, generally don’t require hospitalization.

WATCH | Clinical allergist answers key questions about the Pfizer-BioNTech vaccine:

Dr. Zainab Abdurrahman, a clinical immunologist and allergist, says only one ingredient in the Pfizer-BioNTech COVID-19 vaccine has been known to cause allergic reactions in the past. And the ingredient, polyethylene glycol, is already widely used. The other ingredients are not known to cause allergy. 7:29

On the other hand, as of Jan. 7, COVID-19 had killed more than 16,000 Canadians and put more than 27,000 — about eight per cent of those confirmed to have the disease — in hospital, according to the Public Health Agency of Canada. Around the world, 1.89 million people have died of the disease.

While older adults and those with pre-existing conditions such as obesity and diabetes are more vulnerable, it hasn’t been that rare for young, healthy adults to become severely ill or die. Up to 12 per cent of hospitalized cases during the spring peak in Canada involved people younger than 40.

Why does COVID-19 infection sometimes cause severe illness and death while the vaccine doesn’t?

The goal of a virus is to make copies of itself, and it’s evolved to mess with its host’s innate immune system to facilitate that, by suppressing or “dysregulating” it.

“Unfortunately, with SARS-CoV-2, it seems that in some cases, there is this kind of depression or inhibition of our antiviral response but over-activation of our inflammatory response,” Kelvin said. That can result in massive damage to the body’s tissues, such as lung tissues, without actually clearing out the virus.

The parts of the virus that dysregulate the immune system are generally not present in vaccines.

In fact, while activating the innate immune system is needed to activate the adaptive immune system, the spike protein alone doesn’t do that. That’s why compounds called adjuvants, which generate their own “alarm signals” for the innate immune system, are typically added to protein-based vaccines. But vaccine makers try to keep that response to the minimum required.

Prof. Jen Gommerman, Canada Research Chair in Tissue Specific Immunity at the University of Toronto, says the dose of virus or spike protein a person receives is another factor, and may vary a lot in a natural infection.

With vaccines, clinical trials test different doses and settle on the optimal one.

“This dose is calibrated to initiate a good immune response that doesn’t make you sick,” Gommerman said.

WATCH | Is one vaccine better than the other?

Infectious disease physicians answer viewer questions about COVID-19 vaccines, including if one is better than another and how vaccinations will impact the health-care system. 6:35

Does a COVID-19 vaccine or an infection offer better protection?

Because vaccines don’t induce protection in exactly the same way as a natural infection, one may be more protective or durable than the other, although that depends on the disease. HPV, tetanus and pneumococcal vaccines all induce better immune response than a natural infection, while with some other diseases, an infection may produce more durable protection.

At least one non-scientist, U.S. Sen. Rand Paul, went viral on Twitter with a claim that natural infection with COVID-19 offers better protection than the Pfizer-BioNTech and Moderna vaccines, both of which have shown to be more than 94 per cent effective in late-stage clinical trials.

Actual scientists such as Gommerman and Kelvin dispute this assertion.

So far, both natural infection and vaccination look like they offer relatively effective and long-lasting protection — at least most of a year, based on when the pandemic and vaccine testing began.

Kelvin thinks immunity from vaccination should be as good as that from a natural infection, “or better.”

Grommerman, who has done research testing people for COVID-19 antibodies after infection, shares that opinion. “There is no reason to believe that the immunity elicited by the vaccine would be inferior to that elicited by the virus.” She noted that there’s also the safety risk to consider. “The vaccine has a better chance of making sure that you generate immunity that’s not going to be deleterious.”

Both researchers say the protection from the vaccine is expected to be better than that from a natural infection for at least some people because of the way the virus messes with your immune system, and the fact that the immune response to an infection is extremely variable.

“Some people may make a suboptimal immune response to the natural infection,” Gommerman said, “whereas the vaccine is calibrated to make a robust and strong and appropriate immune response.”

Because the amount of virus you were exposed to, your genetics and other uncontrollable factors play a role in how your immune system responds to an infection, Gommerman recommends the vaccine — and not risking actually getting the disease — to everyone.

“I would say there are no advantages at this point to getting the natural infection as opposed to the vaccine,” she said. “I don’t want people to think, well, if my immune response to SARS-CoV-2 is strong and robust, then maybe I should just get the infection. That would be also the wrong answer, because you’re really rolling the dice. You don’t know if your host immune response is going to be appropriate.”

WATCH | Will masks, distancing be needed after both vaccine doses?

Infectious disease physicians answer viewer questions about the COVID-19 vaccine, including whether masks and physical distancing will be needed after getting both doses of the vaccine and how we’ll know how long immunity lasts. 10:40

In that case, if you’ve had COVID-19, should you still be vaccinated?

Yes, say public health authorities such as the U.S. Centers for Disease Control and Immunize B.C., due to evidence that some people can become reinfected.

Gommerman said that in her research, there are many people who say they’re sure they had COVID-19 but tested negative for antibodies.

Even if you have existing protection, the vaccine will act as a booster.

“You’re simply boosting the immune response and there’s no harm done in that,” she said. “Because of the variability of the immune response to the natural infection, it’s not a bad practice to get that boost.

“Now, should you be at the front of the line? I don’t think so.”

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