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Does SARS-CoV-2 natural infection immunity better protect against the Delta variant than vaccination?

A new study from Israel suggests immunity gained after recovering from a previous COVID-19 infection is more protective against the new Delta variant than vaccine-induced immunity. Natural immunity was estimated to be about 13 times stronger than having two doses of the Pfizer-BioNTech vaccine.

The researchers write:

This study demonstrated that natural immunity confers longer-lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity.”

However, vaccines can add an extra boost to protection in people who recovered from COVID-19. Results showed that a single vaccine dose with natural immunity provided greater protection against reinfection than people with natural immunity alone.

The study “Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections” is published on the medRxiv* preprint server.

How they did it

The research team compared the rate of SARS-CoV-2 infection, the severity of disease, hospitalization, and death in over 16s who had either vaccine-induced or natural immunity.

There were three groups in the study: 673,676 individuals who were fully vaccinated with the Pfizer-BioNTech vaccine and with no prior exposure to SARS-CoV-2; 62,883 unvaccinated individuals who recovered from COVID-19; and 42,099 individuals with prior SARS-CoV-2 infection and who had received a single vaccine dose.

The research team followed up with study participants from June 1 to August 14, 2021. The follow-up period occurred when the Delta variant was common in Israel.

Israel had one of the fastest vaccine rollouts globally. Currently, over 13 million doses have been administered in the country. As a result, the findings make up the largest real-world observational study comparing natural to vaccine-induced immunity.

Increased breakthrough infections and hospitalizations in vaccinated individuals

Vaccinated individuals with no prior exposure to SARS-CoV-2 had a 13.06-fold increased risk of becoming infected with the Delta variant. In addition, there was a 27-fold elevated risk for symptomatic COVID-19 infection.

Although the results could suggest waning natural immunity against the Delta variant, those vaccinated are still at a 5.96-fold increased risk for breakthrough infection and at a 7.13-fold increased risk for symptomatic disease compared to those previously infected,” explained the researchers.

Additionally, vaccinated individuals showed a greater risk of requiring hospitalization from a breakthrough infection than unvaccinated individuals with natural immunity.

People with a single vaccine dose and who previously recovered from infection seemed to have more protection against Delta than unvaccinated people with natural immunity.

There were no COVID-19-related deaths observed in all three groups.

More research investigating the long-term protection of natural immunity is still needed. However, the researchers theorize that natural immunity could be providing a larger immune response towards SARS-CoV-2 proteins than the anti-spike protein immune activation offered by the Pfizer-BioNTech vaccine.

Study limitations and points to consider

The study may have underestimated the number of asymptomatic infections because it collected its data from PCR testing. People with asymptomatic infections are less likely to get tested for SARS-CoV-2, suggesting the results apply primarily to symptomatic infections.

The findings also focused on patients who received the Pfizer-BioNTech vaccine in early 2021. Other research from Israel has recently suggested that vaccine-induced antibody levels wane after several months, but booster shots can enhance immune response. How natural immunity compares to vaccine-induced immunity with booster shots remains unknown.

Additionally, the study findings do not translate to vaccines that are not mRNA-based such as AstraZeneca-Oxford and the Johnson & Johnson vaccines.

The study focused mainly on the Delta variant, which has become widespread in many countries, including Israel. Because Delta was most prevalent during the study, the findings cannot evaluate how natural immunity protects against other SARS-CoV-2 variants.

Lastly, the researchers acknowledge that different health behaviors such as adherence to social distancing and wearing masks could not be controlled for in the study and may have affected the risk of becoming infected.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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