The rate of hospitalization and death is significantly higher after COVID-19 reinfection among unvaccinated US veterans than after breakthrough infection among never-infected vaccine recipients, according to an analysis published yesterday in The Journal of Infectious Diseases.
Researchers from the Veterans Affairs (VA) Pittsburgh Healthcare System and Weill Cornell Medical College created 13,976 matched pairs of vaccinated adults never infected with COVID-19 and unvaccinated COVID-19 survivors using the VA COVID-19 National Database. The median age was 56 years, 91% were men, and 80% were White.
Vaccination was considered receipt of at least two doses of an mRNA vaccine. Of the vaccinated group, 39% had completed only the primary vaccine series, and 61% had also received at least one booster dose.
Similar rates of reinfection, breakthrough cases
Among 13,976 vaccinated veterans not previously infected with COVID-19, 11.2% had a breakthrough infection; among them, 11.8% were hospitalized or died within 28 days. Of the 13,976 unvaccinated, previously infected veterans, 18.3% experienced a reinfection; of them, 17.3% were hospitalized or died.
The rate of breakthrough infection in vaccinated participants resembled that of reinfected unvaccinated participants (0.30 and 0.31 per 1,000 person-days, respectively).
"While overall rates were similar, it is important to note that unvaccinated high-risk subgroups, including those 65 years or older, and those with a higher comorbidity burden were more likely to develop reinfection compared with vaccinated individuals who had a lower rate of breakthrough infections," the researchers wrote.
The hospitalization and death incidence, however, was much higher after reinfection than after breakthrough infection (7.31 vs 4.69). Vaccinated participants were more likely to experience severe infection if they had received their last dose more than 3 months before.
Our study provides strong, direct evidence that vaccinated individuals who develop breakthrough infection are less likely to experience more severe disease outcomes compared with unvaccinated individuals who develop reinfection.
In the first 3 months after either the initial infection or receipt of the last vaccine dose, the unvaccinated group had higher odds of reinfection than the vaccinated group did of having a breakthrough infection.
"This may suggest that vaccination provides stronger earlier protection against reinfection compared with natural infection," the study authors wrote. "The observation of lower reinfection rates 3 and 6 months after first infection compared with breakthrough infection 3 and 6 months after vaccination may indicate longer protection duration from natural infection but may also indicate a depletion of vulnerable individuals early on among the reinfected group."
Individual factors may be at play
"Our study provides strong, direct evidence that vaccinated individuals who develop breakthrough infection are less likely to experience more severe disease outcomes compared with unvaccinated individuals who develop reinfection," the study authors wrote.
This finding has several possible explanations. "Survivors of an initial natural COVID-19 infection may experience severe consequences of infection, which may exacerbate pre-existing comorbidities or lead to development of new comorbidities, which may predispose these individuals to more severe outcomes after reinfection," they wrote. "Conversely, COVID-19 vaccination may prevent such consequences."
Some demographic and behavioral factors may also indirectly protect vaccinated people against severe outcomes. "For example, vaccine acceptance is higher among individuals with higher socioeconomic status and those who also receive other preventive health services like influenza vaccination," the researchers wrote.
"Finally, the immunity generated by natural infection may be quite variable depending on viral and host factors, e.g. severity of initial illness, viral variant, and immune status of the individual," they added.