Due to the rapidly developing body of research, coronavirus disease 2019 (COVID-19) vaccination policies are constantly changing. In fact, several approaches to the allocation of vaccination resources have been introduced, including debates regarding the necessity to administer vaccines to those who have recently recovered from COVID-19.
Study: The Incidence of SARS-CoV-2 Reinfection in Persons With Naturally Acquired Immunity With and Without Subsequent Receipt of a Single Dose of BNT162b2 Vaccine. Image Credit: Mahsun YILDIZ / Shutterstock.com
To date, the short- and long-term effects of hybrid immunity, which is defined as the protection provided by a combination of naturally-acquired and vaccine-induced immunity, are not fully understood. Though many studies on hybrid immunity have been reported, they use limited groups and concentrate on biological evidence, rather than population-based effects. As a result, there remains an urgent need to gather evidence that supports an enhancing effect of vaccination following recovery from COVID-19.
Using the centralized computerized database of Maccabi Healthcare Services (MHS), Israel's second-largest health maintenance organization, researchers compared the incidence rate of reinfection in convalescent and unvaccinated people to that in recovered and single-dose vaccinated people.
About the study
On March 2, 2021, the Israeli Ministry of Health revised its vaccination guidelines to allow for individuals who had recovered from COVID-19 at a minimum of three months prior to their vaccination to receive one dose of the Pfizer-BioNTech BNT162b2 vaccine.
With this in mind, the researchers then began their study by identifying unvaccinated MHS members who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test result by December 2, 2020, which was 90 days before the decision on COVID-19-convalescent individuals and single-dose vaccination recommendations as announced. The study is published in the journal Annals of Internal Medicine.
Multiple nested trials were then conducted, each of which had a different “time zero,” which was followed by a one-week enrolment period where eligible individuals could receive their single dose of the BNT162b2 vaccine. Once these individuals received their single vaccine dose, they were then classified as “previously infected and vaccinated,” and monitored until a SARS-CoV-2 outcome of infection, hospitalization, death, or censoring was reached. Notably, censoring was defined as the end of the follow-up period.
Study findings
Taken together, a total of 41 target trials were included in the current study, which amounted to a total of 107,413 MHS participants who were 16 years and older. Throughout the follow-up period, 1,374 individuals tested positive for SARS-CoV-2, 874 had reinfection that was symptomatic, and 10 were admitted to the hospital with COVID-19-related complications.
During the trial, no COVID-19–related deaths occurred; however, 21,131 people were lost to follow-up and 84,901 people were omitted because they had no recorded COVID-19-related outcomes. Infections that occurred between March 2021 and May 2021 accounted for 0.071% of all positive test results across the whole follow-up period.
When comparing those who had been previously infected but had not been vaccinated with those who had been previously infected but had not been vaccinated, the latter group had a statistically significantly lower risk of reinfection. Additionally, people who had already been infected and immunized had a lower probability of developing symptoms. Considering that just ten people were hospitalized due to COVID-19, there was no statistical significance for this result.
The higher risk of reinfection did not change in a sensitivity analysis that adjusted for the number of PCR tests an individual received throughout the pandemic, as the test frequency score was not significant. A sensitivity examination of symptomatic reinfection yielded similar results.
The authors also calculated the minimum strength required for an unmeasured confounder to skew the data. The E-value for reinfection was 10.84 and 7.9 for symptomatic reinfections.
As a result, a weaker confounder might explain the lower confidence limit. Comparatively, an unmeasured confounder not included in the Cox proportional hazards regression model was linked with both vaccinations after SARS-CoV-2 infection and reinfection outcomes by a hazard ratio (HR) of 10.84 each.
Implications
The current study found that individuals who have been previously infected with SARS-CoV-2 have increased protection following a single dose of a COVID-19 vaccine. Nonetheless, even without an additional vaccine, it appears that reinfection is uncommon, at least in the first year following infection. However, it should be noted that the current study was conducted prior to the introduction of the SARS-CoV-2 Omicron variant, which may alter this observation in real-world settings.
The long-term consequences of SARS-CoV-2 reinfection are still unknown. Therefore, plans for immunization of convalescents of various ages and risk categories will be based on resource prioritization in terms of global vaccination deployment.
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