Omicron variant nearly three-times more likely to cause re-infection

3rd December 2021

The Omicron variant of COVID-19 is potentially three times more likely to cause re-infection suggesting a substantial immune evasion

The Omicron variant (OV) of COVID-19 is potentially associated with a nearly three-fold increased risk of re-infection according to a study by South African researchers from the South African DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis, Stellenbosch University, South Africa.

Although the latest variant was only recently identified in South African where infection rates began to climb, genomic sequencing of the variant indicates that it has between 26 and 32 mutations in the spike protein, many of which are present in the receptor binding domain. However, of more concern is how many of the mutations present are associated with escape from neutralising antibodies and, as a consequence, the currently available vaccines might not be as effective.

B.1.1.529 has been deemed a variant of concern by the World Health Organization although at the present time, a good deal of information about its transmissibility, the level of disease severity and effectiveness of current vaccines remains unknown. With the appearance of an increasing number of COVID-19 variants, one key question is whether these can lead to re-infection either after natural or acquired immunity from vaccination.

For the present study, the South African team set out to determine whether the risk of re-infection had changed over time by examining rates of re-infection and whether the OV might had impacted on these rates. They used epidemiological data from the National Institute for Communicable Diseases and the line list of repeated COVID-19 tests and all positive tests are recorded in the combined data sets. Although these data are recorded as de-identified cases, the presence of repeat cases were used to calculate the time between consecutive positive tests for these individuals. Using the dates of reported infection, the researchers were able to calculate the time between successive infections for each person and the period of analysis was from the start of the pandemic in March 2020 and to the end of November 2021.

Findings

A total of 35,670 individuals with at least two suspected infections were identified, although 332 had three infections and one individual at least four. Re-infections showed a bimodal distribution, peaking near 180 and 360 days, representing the first and second waves of the pandemic.

However, for the more recent second infections (after October 2021), there were a higher number of re-infections among individuals whose primary infection had occurred during the third wave. In addition, since mid-November, re-infections were occurring in those whose primary infection had been during the first and second waves. Among those who had more than one infection, 47 experienced the third infection in November 2021 and which the authors suggested could be associated with the omicron variant.

Using regression modelling, the team determined the relative hazard ratio for re-infection to be 0.75 (95% CI 0.59 – 0.97) for wave 2 versus wave 1 and for wave 3 versus wave 1 it was 0.71. However, the hazard ratio for the period from 1 November 2021 to 27 November versus wave 1 was 2.39 (95% CI 1.88 – 3.11), i.e., the risk of re-infection was almost three times higher during November 2021.

Commenting on these findings, the authors suggested that risk of re-infection compared to a primary infection had reduced over the three waves and which was to be expected as the population gained greater immunity, even in the presence of the beta and delta variants. However, the increased rate of re-infection during November 2021 suggested that the rise was driven by the OV, although they couldn’t be certain because not all of the samples had been sequenced.

They concluded that there was evidence of a substantial increase in the risk of re-infection that has coincided with the emergence of the OV in South Africa which seemed to have a greater ability to re-infect previously infected individuals.

Citation

Pulliam JRC. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. MedRxiv 2021

Vaccine breakthrough shown to occur in practice with COVID-19 South African variant

13th April 2021

In vitro neutralising assays suggest an increased escape for some COVID-19 variants of concern but whether this occurs in real world settings remains largely unknown.

Two COVID-19 mutations labelled “variants of concern (VOC)” are the ones first identified in the UK (B.1.1.7) and South Africa (B.1.351). According to the World Health Organization, a variant of concern is one for which there is evidence of increased transmissibility, more severe disease or a significant reduction in neutralisation by antibodies. In vitro data on neutralisation of VOC are mixed, with some studies indicating that vaccines such as the BNT162b2 offer a high level of protection whereas others show a significant reduction in neutralisation. Nevertheless, whether vaccines offer sufficient protection against these VOCs in clinical practice is uncertain. In trying to assess whether these VOCs could overcome the immune response generated by vaccination with BNT162b, a team of Israeli doctors from Clalit Health Services, Haifa and Western Galilee, Israel, performed a case-controlled study to examine whether BNT162b-vaccinated individuals with documented COVID-19 infection were more likely to be infected with either VOC compared with unvaccinated individuals. Their hypothesis was the both VOCs were able to surmount protection offered by the BNT162b vaccine and identified patients with documented COVID-19 and matched them to an unvaccinated control.

Findings
Data were available for 149 individuals who had been fully vaccinated and tested positive. Complete viral genome sequencing was performed and revealed how B.1.1.7 was the predominant strain of the virus in circulation whereas the B.1.351 variant was present in less than 1% of the samples. Among those who were fully vaccinated, 5.4% were infected with B.1.531 compared to 0.7% of unvaccinated individuals. In contrast, there was no difference in the rates of infection with B.1.1.7 in vaccinated and unvaccinated individuals (89.9% vs 92.6%).

Commenting on their results, the authors noted that while their study was not designed to examine the effectiveness of the BNT162b vaccine against the different VOCs, the data shows an increased incidence of B.1.351 in vaccine breakthrough among fully vaccinated individuals. However, given that the incidence of B.1.351 in circulation was very low, the authors suggested that selection did not favour this latter VOC but felt how their results emphasised the importance of tracking viral variants and that vaccination was the safest and most effective means of preventing onward transmission of the virus.

Citation
Kustin T et al. Evidence for increased breakthrough rates for SARS-CoV-2 variants of concern in BNT162b mRNA vaccinated individuals. Med Rxiv 2021