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Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa

Our take —

This retrospective study, available as a preprint and thus not yet peer-reviewed, assessed whether the emergence of the Omicron SARS-CoV-2 variant of concern was associated with an increased risk of reinfection using data for all positive test results in South Africa between March 4, 2020, and November 27, 2021 (n= 2,796,982). Suspected reinfection (two positive tests >90 days apart) was identified for 35,670 participants. Two statistical models were used to assess changes in risk—one based on a constant hazard of reinfection throughout the study period, and one based on time-varying hazards of primary infection and reinfection. Both approaches demonstrated that the emergence of the Omicron variant was associated with an increased risk of reinfection. For the second model, the hazard ratio for reinfection vs. primary infection following the introduction of the Omicron variant was 2.39 (95% CI: 1.88–3.11), demonstrating population-level evidence of immune escape, a finding not observed with emergence of either Beta or Delta variants. This study demonstrates the risk that the Omicron variant poses for reinfection in the setting of high rates of prior SARS-CoV-2 infection. Additional research is urgently needed to assess the ability of prior infection and/or vaccination to protect against severe disease and death from Omicron.

Study design

Retrospective Cohort

Study population and setting

This study examined whether the emergence of the Beta, Delta, and Omicron SARS-CoV-2 variants of concern led to increased risk of reinfection in South Africa. Study data included all laboratory-confirmed SARS-CoV-2 positive test results received by the Notifiable Medical Conditions Surveillance System (NMC-SS) between March 4, 2020, and November 27, 2021 (n= 2,796,982). For the sake of consistency and data completeness, the date that each specimen was received in the lab was used as a proxy for calendar date of infection. Reinfection was defined as two positive SARS-CoV-2 tests at least 90 days apart for the same participant. Two statistical approaches were used to assess changes in risk of reinfection over time. In the first approach, observed reinfection patterns were compared to a null model that assumed risk of reinfection was proportional to overall incidence with a constant hazard coefficient. In the second approach, empirical hazard coefficients for primary infection vs. reinfection were calculated at each time point and compared over time. A sensitivity analysis was conducted to assess the impact of vaccination.

Summary of Main Findings

The study population included 35,670 participants with at least two suspected SARS-CoV-2 infections. Using the first approach (constant hazard of reinfection), the emergence of the Omicron variant was associated with an increase in observed vs. projected reinfections, which is a signature of immune escape. Similar deviations from the null model were not observed after the introduction of the Beta or Delta variants. Using the second approach (time-varying hazards of primary infection and reinfection), the emergence of the Beta and Delta variants was associated with an increased hazard of primary infection without corresponding changes to the hazard of reinfection. In contrast, the introduction of the Omicron variant was association with a decreased hazard of primary infection and an increased hazard of reinfection; the hazard ratio for reinfection vs. primary infection in November 2021 was 2.39 (CI: 1.88–3.11). Sensitivity analyses demonstrated that vaccination may be partially responsible for the observed decline in the hazard of primary infection, but vaccine coverage during the study period was quite low.

Study Strengths

This study analyzed a large, comprehensive national data set for all confirmed SARS-CoV-2 cases in South Africa. Results were consistent between both statistical approaches used.

Limitations

These analyses do not account for changes in testing practices, rates of detection, participant behavior, participant demographics (age, occupation, socioeconomic status), or healthcare access which may have occurred over the course of the pandemic. Results from rapid antigen tests may be underreported despite mandatory reporting requirements, so the study may underestimate rates of both primary infection and reinfection. Civil unrest in July 2021 in Gauteng and KwaZulu-Natal provinces may have also led to underreporting of test results and underestimation of infections during this period. Reinfection was not confirmed by sequencing and did not require negative test results between primary infection and reinfection. Symptom severity in primary infection vs. reinfection was not assessed because these data were not collected. While vaccine coverage in South Africa was low during the study period, vaccination may have impacted hazards of both primary infection and reinfection. The vaccination status of individual study participants was unknown.

Value added

This study demonstrated early population-level evidence of an increased risk of SARS-CoV-2 reinfection immediately following the emergence of the Omicron variant in South Africa.

This review was posted on: 15 December 2021