A population-level study conducted on residents of the Quebec province, Canada, has demonstrated that prior infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces robust and long-lasting protection against omicron re-infection and hospitalization. The level of protection further increases with coronavirus disease 2019 (COVID-19) vaccination. The study is currently available on the medRxiv* preprint server.
Study: Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination. Image Credit: NIAID
Background
The most recently emerged omicron variant of SARS-CoV-2 is phylogenetically and antigenically different from previously circulating variants of concern (VOCs). A heavily mutated spike protein has significantly increased the omicron variant’s transmissibility and immune evasion ability, leading to a global rise in breakthrough infections even in countries with high vaccine coverage. However, despite the high infection rate, the omicron variant has been found to cause comparatively less severe infections.
Given the global predominance of the omicron variant, it is vital to assess whether prior SARS-CoV-2 infection and/or COVID-19 vaccination can reduce the risk of omicron re-infection and severity.
In the current study, the scientists have conducted a population-level analysis to estimate the degree and duration of protection provided by prior SARS-CoV-2 infection against omicron re-infection and hospitalization. Furthermore, they have assessed the effectiveness of first, second, and third doses of mRNA-based COVID-19 vaccines (Pfizer and Moderna) against omicron infection in individuals with and without prior infection.
Study design
The study was conducted on Quebec residents (age: 12 years and above) who were tested for SARS-CoV-2 via reverse transcription-polymerase chain reaction (RT-PCR). The cases were defined as SARS-CoV-2 test-positivity and the controls were defined as SARS-CoV-2 test-negativity during the study period (December 2021 – March 2022).
The analyses were conducted to estimate the proportion of PCR-confirmed SARS-CoV-2 infection and COVID-19-related hospitalization during the study period.
Important observations
A total of 224,007 test-positive cases and 472,432 test-negative controls were included in the analysis. Of all cases, 4.2% were re-infections. Taking the vaccination status into account, 0.4% of primary infections were in individuals not vaccinated, 0.2% were incurred after vaccination, and 3.7% occurred before vaccination.
A total of 5,057 cases with hospitalization were identified. Of them, 1.3% were with previous SARS-CoV-2 infection. No deaths were observed among hospitalized COVID-19 patients with prior infection.
Protection against omicron re-infection induced by prior infection
About 44% reduction in the risk of omicron re-infection was observed among unvaccinated individuals with prior non-omicron infections. A positive correlation was observed between the severity of primary infection and the risk of re-infection. About 8%, 43%, and 68% reduction in re-infection risk was observed in individuals with previous asymptomatic infections and symptomatic infections not-requiring and requiring hospitalization, respectively.
Prior infection and mRNA vaccine effectiveness against Omicron reinfection stratified by number of doses and timing before or after primary SARS-CoV-2 (non-Omicron) infection, relative to non-vaccinated with no infection history
Regarding the duration of protection, previous asymptomatic infections were found to provide protection against re-infection only for the first 6 months. Overall, prior non-omicron infections were found to reduce the risk of re-infection by 66% for 3 – 5 months, by 35% for 9 – 11 months, and by less than 30% for subsequent months.
Protection against omicron re-infection induced by vaccination
The COVID-19 vaccines were found to provide 65%, 68%, and 83% protection against omicron re-infection after first, second, and third doses, respectively, in previously infected individuals. In contrast, in individuals without prior infection, only 20%, 42%, and 73% protection were observed after the first, second, and third vaccination.
No matter how many vaccinations were administered, previously-infected individuals had 40-60% greater protection against re-infection. However, for both previously-infected and non-infected individuals, the three-dose vaccination regimen provided significantly higher protection than the two-dose regimen.
Protection against omicron-related hospitalization by prior infection and vaccination
About 81% reduction in hospitalization risk was observed among unvaccinated individuals with prior non-omicron infections.
In previously infected individuals, about 86%, 94%, and 97% protection against hospitalization was observed after the first, second, and third vaccine doses, respectively.
In previously non-infected individuals, about 52%, 76%, and 91% protection was observed after the first, second, and third vaccine doses, respectively.
According to the study, the protection against hospitalization among previously infected individuals was higher by about 70% to 80% compared to non-infected individuals regardless of the number of doses of vaccine administered.
In previously infected individuals, the two-dose vaccination regimen was found to provide long-lasting protection (11 months post-vaccination). However, in previously non-infected individuals, a significant reduction in protection was observed after 6 months post-second vaccination.
Study significance
The study highlights that prior infections with non-omicron variants provide a high level of protection against omicron re-infection and hospitalization. Furthermore, the highest protection has been observed in previously-infected individuals who have received three doses of a COVID-19 vaccine.
*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.
