In a recent study posted to the medRxiv* preprint server, researchers evaluated protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection.
In general, the global population harbors a heterogeneous immune history due to multiple exposures to SARS-CoV-2 variants and vaccination. Evidence suggests that prior SARS-CoV-2 infection could negatively imprint subsequent protective immunity. Specifically, immune responses against SARS-CoV-2 Omicron sub-variants could be compromised due to differential imprinting in individuals with a previous infection with ancestral SARS-CoV-2 or pre-Omicron variants.
About the study
The present study investigated epidemiologic evidence for immune imprinting in the Qatari population. The researchers obtained data on SARS-CoV-2 laboratory testing, vaccination, hospitalization, and deaths, from the national digital-health information platform.
The incidence of SARS-CoV-2 reinfection with Omicron BA.1 or BA.2 in individuals previously infected with pre-Omicron variants (reinfection cohort) was compared to the incidence of reinfection in individuals with a documented primary Omicron infection (primary infection cohort).
Individuals with a documented reinfection from December 19, 2021, to August 15, 2022, were included in the reinfection cohort. In the same period, those with primary infection (Omicron) were included in the primary infection cohort. The study’s primary outcome was the incidence of SARS-CoV-2 infection; secondary outcomes included the incidence of severe, critical, or fatal coronavirus disease 2019 (COVID-19).
Reinfection cohort individuals were exact-matched in a 1:3 ratio to those in the primary infection cohort based on sex, nationality, comorbidities, and the calendar week of primary or reinfection. Reinfection was defined as recurrence of infection a minimum of 90 days after primary infection. Subjects were followed up until a documented SARS-CoV-2 infection, vaccination, or death occurred.
The team computed the cumulative incidence of infection using the Kaplan-Meier estimator method. Hazard ratios (HRs) and corresponding 95% confidence intervals were estimated using Cox regression, adjusting for matched variables. Additionally, a subgroup analysis was performed to compute adjusted HRs by time since reinfection.
Findings
After matching, the reinfection cohort comprised 7,873 individuals, while the primary infection cohort had 22,349 subjects, all of whom were not vaccinated. There were 63 and 343 reinfections in the reinfection and primary infection cohorts, respectively. None in either cohort developed severe COVID-19 outcomes. The cumulative incidence of SARS-CoV-2 infection was 1.1% and 2.1% for the reinfection and primary infection cohorts, respectively, after 135 days of follow-up.
When the incidence of infection was compared between the two cohorts, the adjusted HR was estimated at 0.52. The adjusted HR was 0.59 in a subgroup analysis where primary infections in the reinfection cohort were limited to ancestral SARS-CoV-2 or the Alpha variant. The adjusted HR was 0.92 in the first 70 days of follow-up when Omicron BA.2 was prevalent.
Around 45% and 38% of the subjects in the reinfection and primary infection cohorts underwent SARS-CoV-2 testing during the follow-up period, with a frequency of 0.79 and 0.64 tests/individual, respectively. After adjusting for the testing frequency between the two cohorts, the HR was 0.42, confirming the findings.
Conclusions
The study found no evidence that immune imprinting compromised protective immunity against SARS-CoV-2 Omicron sub-variants. The authors found that primary infection with pre-Omicron variants and reinfection with Omicron resulted in more robust protection against subsequent Omicron sub-variants than (primary) infection with Omicron alone.
Notably, undocumented or missed infections might have boosted immune responses, given that only documented infections were examined. Moreover, the findings could not be generalized to populations from other countries and older adults because most of Qatar’s population is predominantly young.
*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.
