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Experts identify potential bias in CDC natural immunity study

A medical staffer prepares a dose of the coronavirus (COVID-19) vaccine at a vaccination pop-up site. (Photo by Michael M. Santiago/Getty Images)
A medical staffer prepares a dose of the coronavirus (COVID-19) vaccine at a vaccination pop-up site. (Photo by Michael M. Santiago/Getty Images)
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Some epidemiologists describe a government study comparing vaccine and natural immunity as potentially biased.

The director of the Centers for Disease Control and Prevention, Dr. Rochelle Walensky, recently tweeted that people who were unvaccinated and had a prior COVID-19 infection “were 5X more likely to have COVID-19” than those who were vaccinated without natural immunity. She referred to an Oct. 29 CDC study that examined patients who were hospitalized with “COVID-19–like illness.”

Despite the conclusion one might draw from Walensky’s tweet, the CDC study isn’t designed to answer the question of whether vaccine immunity or natural immunity is superior. Harvard Medical School professor Martin Kulldorff, an epidemiologist and biostatistician who now serves as senior scientific director of Brownstone Institute, writes that the study instead answers the question of “whether vaccination or Covid recovery is more related to Covid hospitalization or if it is more related to other respiratory type hospitalizations."

There is both a relationship between being vaccinated/recovered and Covid hospitalization and a relationship between being vaccinated/recovered and non-Covid hospitalization,” Kulldorff continues. “Rather than evaluate the first one, which is of intense interest for health policy, the CDC study evaluates the contrast between the two, which is not particularly interesting.

The CDC study also appears to conflict with a major Israeli study from August. That study showed unvaccinated people with natural immunity had far greater protection than vaccinated people without natural immunity. Specifically, the vaccinated group was 13 times more likely to experience a future infection and 27 times more likely to experience a symptomatic future infection.

Dr. David Dowdy, associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, says there are “potential challenges” with the CDC study, as well as challenges with the Israeli study.

The CDC study only focuses on individuals who are hospitalized, i.e., people who contract disease serious enough to get them hospitalized. This means the participants may not represent the general population, Dowdy says.

“Long story short, this is not a representative population of people who are vaccinated or people who had COVID before,” Dowdy says. “I’m not sure that I would necessarily have any reason to believe that it’s more likely to be biased or in favor of the vaccine as opposed to previous immunity, but it certainly runs the risk of being biased. And the number you would get here is not the number you would get in the general population.”

The ideal study design, Dowdy says, would involve following a vaccinated group and naturally immune group over time to see what the probability is of contracting the virus. The time element makes this type of study more difficult to perform, and the CDC chose to analyze a group of people at one point in time.

“It’s a simpler approach because you can do it faster,” he said.

But Dowdy says the Israeli study is subject to its own challenges involving geographical distribution.

People who are more likely to be vaccinated or more likely to be naturally immune may live in different areas. Wealthier people tended to get vaccinated earlier, for example, while the less-wealthy tend to get infected earlier. It’s possible that a person’s risk to COVID has a lot to do with whether their area suffered an outbreak, regardless of vaccination or natural immunity rates.

It would be very easy to have outbreaks that are just based on where people live. And so it looks like vaccination isn’t good, but that’s just because you had an outbreak in a certain city that had a lot of people vaccinated,” Dowdy said.

Although the Israeli researchers note that they matched participants according to “residential socioeconomic status,” Dowdy says no study matching is perfect.

“This is the nature of science, right? We never have perfect populations,” he said. “I think when you take the totality of all the evidence, it’s hard to say convincingly that one or the other is better — previous infection versus vaccination.”

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In August, the CDC published a separate study on the vaccine and natural immunity. The headline of the CDC’s news release read, “Vaccination Offers Higher Protection than Previous COVID-19 Infection.” That study also did not directly compare immunity from vaccination with immunity from prior infection, but instead showed that, among people with natural immunity, those who also were vaccinated received “additional protection.”

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