Why Do Some People Never Get COVID-19?


Verywell Health / Ellen Lindner

  • Researchers are trying to understand why some people never get COVID-19 despite exposure.
  • One study is exploring whether genetic factors play a role in making someone immune to the virus.
  • Another study investigated preexisting immunity, potentially brought on by infections with other coronaviruses.

Scientists are looking into what makes someone part of the “never COVID” cohort. This is the name researchers have given people who were exposed to the virus—without or before vaccine protection—who have never contracted the virus.

They are analyzing whether some people’s genetics or immune response to previous viruses might help protect them from COVID-19.

Learning why some people never get COVID-19 despite exposure may help researchers find better ways to support high-risk patients. Plus, through similar research scientists have found novel ways to combat other infectious diseases.

“Even if we move from the pandemic phase to the endemic phase, coronaviruses are here to stay,” Jagdish Khubchandani, PhD, professor of public health at New Mexico State University, told Verywell. “And we definitely want to know more about them in anticipation of future behaviors of these viruses.”

Do Genetics Make Some People Immune to COVID-19?

An international team of researchers is in the process of recruiting potential study participants who fit the so-called “never COVID” cohort. They are looking for people who were exposed to someone with COVID-19 for a lengthy period, without protection, and never got sick or tested positive for the virus.

For example, in some cases an entire family contracted the virus, except for one person, despite living in close quarters and not yet having some protection from vaccination. The researchers detailed their efforts in a journal article published in Nature Immunology.

“The gene study being conducted is an attempt to explore unique genetic and immune characteristics that make individuals vulnerable to or immune to COVID-19,” said Khubchandani, who is not involved in the research.

Finding enough individuals who meet the research criteria is posing a challenge. “One factor the study specifically calls out as a difficulty is the ability to definitively determine whether a participant has or hasn’t experienced a COVID-19 infection despite exposure,” Rebekah Sensenig, DO, an infectious disease expert with Riverside Health System, told Verywell.

“While PCR and other tests can offer us a snapshot in time, we don’t currently have the capabilities to detect former or future infections with 100% certainty,” added Sensenig, who is not involved in the research.

As of now, the study team doesn’t know the specific mechanisms that might make someone resistant to COVID-19 infection. But they theorize that some people may have differences in the ACE2 receptor, which the virus needs for cell access.

A genome-wide association study (GWAS), which has not yet been peer-reviewed, does show a variant that down-regulates the expression of this receptor, potentially decreasing the risk of contracting COVID-19.

Similar research has uncovered that genetic variations in certain cell receptors can make people resistant to a type of malaria, HIV, and noroviruses. Such discoveries have even led to new HIV medications and treatments.

“Depending on the findings of the ‘never COVID’ cohort study, there is an opportunity to use the same principle to help treat those severely impacted by the COVID-19 virus,” Sensenig explained.

Do Prior Viral Infections Provide COVID-19 Immunity?

Another study, published in Nature Communications, shows that some individuals have what might be a pre-existing immunity to COVID-19.

“The hypothesis is that people with increased exposure to other versions of coronaviruses will have ‘premade’ T cells that cross-react with COVID-19 and are able to quickly respond to COVID-19 infection,” Sensenig explained. For example, other human coronaviruses are responsible for the common cold.

The researchers compared the polymerase chain reaction (PCR) testing status and immune response of 52 people after COVID-19 exposure from someone in their household. The 26 people who tested negative had a higher frequency of cross-reactive memory T-cells compared to the 26 people who eventually tested positive for the virus.

“Specific memory T-cells are one of the primary cellular vehicles of immunity,” J. Wes Ulm, MD, PhD, who was not involved with the research, told Verywell. “It’s quite intriguing that these individuals are essentially immune to COVID-19 development, at least partially, despite not having been vaccinated or [not having] experienced a prior infection.”

What This Means For You

Researchers are looking into genetic, immune, and other factors that may help protect some individuals from COVID-19. But they say the best way to protect yourself from severe illness is to continue to follow vaccination and boosting recommendations and to wear a mask when appropriate.

Other Reasons People Haven’t Tested Positive

In addition to potential immune system or genetic factors, other people may have never developed COVID-19 if they evade exposure.

For example, some people have had the ability to work from home or practice rigorous social distancing. Masking and following vaccination and booster recommendations from public health experts prevented many infections, as well. Other people may have had a mild or asymptomatic case of COVID-19 but never got tested.

“There could be multiple demographic, genetic, behavioral, and immune related factors peculiar to individuals that could make them more vulnerable or resistant to infection with COVID-19 and predict the outcomes of the infection,” Khubchandani said.

But the research examining these factors can help pave the way for better understanding of COVID-19 and other infectious diseases, he added.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Mallapaty S. The search for people who never get COVIDNature. 2021;599(7884):191-191. doi:10.1038/d41586-021-02978-6

  2. Andreakos E, Abel L, Vinh DC, et al. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infectionNat Immunol. 2021;23(2):159-164. doi:10.1038/s41590-021-01030-z

  3. Horowitz JE, Kosmicki JA, Damask A, et al. Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease. MedRxiv. Preprint posted online June 10, 2021. doi:10.1101/2020.12.14.20248176

  4. Kundu R, Narean JS, Wang L et al. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contactsNat Commun. 2022;13(1). doi:10.1038/s41467-021-27674-x

By Jennifer Chesak
Jennifer Chesak is a medical journalist, editor, and fact-checker with bylines in several national publications. She earned her Master of Science in journalism from Northwestern University's Medill School. Her coverage focuses on COVID-19, chronic health issues, women’s medical rights, and the scientific evidence around health and wellness trends.