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Natural immunity vs vaccination in people previously infected with COVID-19


Although prior infection and vaccination have been found to significantly protect against COVID-19 infection, vaccination in previously infected individuals only provided additional protection against symptomatic COVID-19 among those who received the vaccine several months after the initial onset of the disease. These findings were published in Clinical infectious diseases.

To assess the need for vaccination in people previously infected with COVID-19, researchers conducted a retrospective cohort study among people employed at the Cleveland Clinic in Ohio. Participants with at least 1 positive test result for COVID-19 infection were considered previously infected. The primary outcome was time to COVID-19 infection. Researchers analyzed the cumulative incidence of COVID-19, symptomatic COVID-19, and COVID-19 hospitalizations for 1 year after COVID-19 vaccines became available in the United States.

At the end of the study, 4,718 (9%) and 36,922 (71%) of a total of 52,238 enrolled participants had respectively been previously infected or vaccinated against COVID-19 infection. Of all participants included in the study, 7851 (15%) became infected with COVID-19 during the study period, of which 4675 (60%) had symptomatic infections and 133 (1.7%) had to be hospitalized. Among participants infected with COVID-19 during the study period, 4,936 (63%) and 2,915 (37%) were infected within 11 months before or within one month after first detection of the variant Omicron in the United States, respectively. Of note, the cumulative incidence of COVID-19 infection increased significantly in unvaccinated participants without prior COVID-19 infection.

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The researchers analyzed the results in a Cox proportional hazards regression model and found that prior infection and vaccination were independently associated with a significantly reduced risk of incident COVID-19 infection. Among participants without prior COVID-19 infection, vaccination was associated with a significant decrease in the risk of a COVID-19 incident both in the period before the emergence of Omicron (relative risk [HR], 0.26; 95% CI, 0.24-0.28) and time after Omicron emergence (HR, 0.48; 95% CI, 0.44-0.53). In patients who were previously infected with COVID-19, the researchers noted that vaccination was not associated with a significant decrease in the risk of a COVID-19 incident nor in the period before (HR, 0.78 95% CI, 0.31-1.96) nor after emergence. of the Omicron variant (HR, 0.77; 95% CI, 0.53-1.12). Among participants with prior COVID-19 infection, in the periods before and after the emergence of the Omicron variant, vaccination was associated with a significantly decreased risk of symptomatic COVID-19 (RR, 0.60; CI 95%, 0.40-0.90 versus HR, 0.36; 95% CI, 0.23-0.57, respectively).

Based on further analysis of the results, the researchers estimated that the duration of protection against COVID-19 infection conferred by natural immunity in unvaccinated participants was 1 year or more for the period before the emergence of Omicron.

Limitations of the study included a lack of routine testing among asymptomatic participants, as those previously infected who remained asymptomatic were potentially misclassified as previously infected. Additionally, the study included no children, few older adults, and only a small number of immunocompromised participants, so the results may not be generalizable to other patient populations.

According to the researchers, “both previously infected people and those who [have] vaccinated are substantially protected against COVID-19 infection, but protection against natural and vaccine-induced immunity declines over time and is inherently less potent against the Omicron variant. They concluded that “prior infection should be considered in COVID-19 vaccination recommendations.”


Shrestha NK, Burke PC, Nowacki AS, Terpeluk P, Gordon SM. Need for vaccination against COVID-19 in people who have already had COVID-19. Blink Infect Dis. Published online January 13, 2022. doi: 10.1093/cid/ciac022