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In the pre-Omicron variant era, previous symptomatic COVID-19 infection in unvaccinated patients conferred a level of protection against subsequent infections on par with that of mRNA vaccines but longer-lasting, according to a US study of more than 121,000 participants published today in JAMA Network Open.

The findings, of course, do not suggest that infection is preferred over vaccination, which is the much safer alternative.

University of Chicago researchers led the study, using data from COVID-19 test results at 1,300 sites in six western states at Providence Health & Services from Oct 1, 2020, to Nov 21, 2021. Both vaccinated and unvaccinated patients were monitored for COVID-19 infection starting 90 days after vaccination or initial illness.

A total of 24,043 unvaccinated, previously infected patients and 95,572 vaccinated patients (controls) tested positive during the study period. Among them, 0.4% of previously infected patients and 2.8% of controls tested positive for COVID-19 during the study period.

Previous COVID-19 was tied to protection of 85% against reinfection, 88% against hospitalization, and 83% against COVID-19 not requiring hospitalization. This protection remained stable with no waning up to 9 months after the initial illness.

The hazard ratio (HR) for testing positive for COVID-19 among previously infected patients was 0.15 (95% confidence interval [CI], 0.13 to 0.18), while it was 0.12 (95% CI, 0.08 to 0.18) for COVID-19 hospitalization, and 0.17 (95% CI, 0.13 to 0.21) for infection not requiring hospital admission.

The study authors said that their findings are similar to those of previous studies, which found protection against COVID-19 afforded by previous infection of 80.5% to 100%. "The findings of this study may have important implications for vaccine policy and public health," they wrote.

The results, the researchers said, "suggest that natural immunity was associated with similar protection against mild and severe disease," they added. "mRNA vaccines are associated with similar prolonged protection from severe COVID-19 as found in our study, although vaccine-associated protection from mild COVID-19 has been shown to wane at 6 months."

In a Providence press release, senior author Ari Robicsek, MD, said that while previous infection provided similar protection as mRNA COVID-19 vaccination, "vaccination is a considerably safer way to acquire that immunity."

Study limitations include the possibility that participants may have undergone COVID-19 testing or vaccination at a healthcare facility outside of the Providence system, and COVID-19 survivors may behave differently than coronavirus-naïve participants, the researchers cautioned. "Strengths include large sample size, long duration of follow-up, and inclusion of only unvaccinated individuals with symptomatic COVID-19," they wrote.

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