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expert reaction to preprint looking at risk of reinfection associated with emergence of the Omicron variant in South Africa

A preprint, an unpublished non-peer reviewed study, looks at the risk of SARS-CoV-2 reinfection associated with the Omicron variant in South Africa.


Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“This set of real world data on the ability of the Omicron variant provide us with the first indication that it is indeed able to evade immunity conferred by previous Covid-19 infection.  There are a few caveats in this work, such as not having definitively confirmed that it was indeed Omicron that was causing the reinfection, but they were able to determine that the increased transmission of Beta or Delta variants was not a result of immune evasion. Researchers studied over 35,000 suspected reinfections at least 9 months apart and found that Omicron has a substantial ability to evade immunity resulting from previous infection. 

“There is no indication as to how this immune evasion happens, although it can be presumed to be because of decreased antibody binding to Omicron’s mutated spike protein.  But decreased T-cell immunity cannot be excluded as a possible contributory factor.

“Omicron has blown a big hole in the controversial argument that we should simply allow the infection to spread in an attempt to create immunity.  Herd immunity which now seems like nothing more than a pipe dream.  We await a further indication as to whether Omicron has any ability to evade vaccine induced immunity.”


Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:

“The preprint posted by Pulliam and colleagues is the first such report on the transmission from the omicron variant. The authors were able to get this report in the public domain as they had only recently (11th November) published a report of reinfections in South Africa. What they have done here is updated this previous paper to include new data from recent weeks up to the 27th November to give the first indication of the epidemiology of omicron. That they have been able to get this report together so quick is a credit to the South African authors as well as a big helping of serendipity from having a paper already completed.

“Essentially the authors looked at the rate of reinfection in people (a reinfection with a positive sample occurring 90 days after the last positive specimen). The authors used two different modelling approaches to analyse national routinely collected data both at national and regional levels. The authors were not able to determine the severity of infection in the dataset they were using. The analysed data during the waves associated with the beta variant, and the delta variant and in this resubmitted pre-print the omicron variant.

“Essentially, they found that the second (beta) and third (delta) waves were not associated with increased risk of reinfection, though they point out that this observation is at odds with the results of laboratory based viral neutralisation studies which did suggest some immune escape. However, the risk of re-infection in the current wave or at least 1st to 27th November is more than twice as great as previously greater (Relative hazard Ratio 2.39 (95% confidence intervals 1.88 to 3.11).

“This finding is consistent with the hypothesis that unlike previous waves that were because the variants were intrinsically more infectious, omicron appears to be have substantial immune escape at least from immunity caused by a natural infection. Whether omicron is also more infectious is possible but cannot be answered by this analysis. This analysis is also not able to determine how much omicron can escape from immune control following vaccination, though if it can escape natural immunity it is also likely to have substantial escape potential for vaccine induced immunity.

“The implications of this paper are that omicron will be able to overcome natural and probably vaccine induced immunity to a significant degree. But, the degree is still unclear though it is doubtful that this will represent complete escape. The other big uncertainty is whether this increases the risk of severe disease, hospital admissions and deaths. With previous variants epidemiological studies showed that protection against severe disease from other variants was better maintained than protection against infection. It remains to be seen how much protection against severe disease is maintained for the omicron variant.

“But even if protection against severe disease is maintained, if case numbers increase dramatically then the pressure on hospitals will also probably rise.

“It remains the case that the extra value of the booster vaccination dose remains the most important step that we can take to reduce the probability of severe disease. I suspect new targeted vaccinations will be developed against omicron but it the infection spreads globally as rapidly as it seems to be taking off in South Africa then most of us may already have had the infection by the time a new vaccine is available.”


Prof Francois Balloux, Professor of Computational Systems Biology and Director, UCL Genetics Institute, UCL, said:

“The study is based on nearly three million people with laboratory-confirmed SARS-CoV-2 in South Africa. It reports 35,670 suspected reinfections throughout the pandemic. Risk of reinfection by the omicron variant was estimated to be around three times higher than by the alpha and delta variant.

“The higher estimated reinfection ability of the omicron variant to cause reinfection is not overly surprising and could be largely anticipated based on the large number of mutations in the spike protein caried by the omicron variant, which increase the omicron variant’s ability to bypass host immunity.

“The study is competently performed and highly timely as it provides the first direct evidence for the increased ability of the omicron variant to partially bypass prior host immunity conferred by prior infection.

“Though, since the study is strictly correlative, some confounders such as waning levels of immunity could not be taken into account. It remains that it provides a plausible estimate for the increased rate of reinfection by the omicron variant.

“The study does not provide any insight on the robustness of vaccine induced immunisation against the omicron variant. It also does not report any data on infection severity. South Africa has a low vaccination rate but a large proportion of the population has been infected during previous Covid-19 waves. The population of South Africa also tend to be fairly young with a median age of 27.6 years.

“As such, the results from this study are not directly portable to other settings such as Europe or North America and more data will be needed before we can make more any robust prediction about the potential threat posed by a global spread of the omicron variant in different parts of the world.”


Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“The South Africa team deserve great credit for putting together a high-quality analyses in a short period of time, all the more so with the world watching and waiting. This analysis does look very concerning, with immunity from previous infections being relatively easily bypassed. Might this all still be a ‘false alarm’? That is looking less and less likely.

“We do not yet have up to date information on vaccine effectiveness. However, the situation should, to some extent, be different with vaccine-generated immunity. The immune response from vaccination is much stronger when compared with infection-acquired immunity. Whilst there is likely to be some impact, it is likely vaccines will still provide some level of protection. The booster dose may be key here in maintaining a high level of protection. Whilst we await more data to emerge over the coming days and weeks, the message to the general public has to be – go and get all the doses you are eligible for. Keep that protection as high as possible.”



‘Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa’ is a preprint by Juliet R.C. Pulliam et al.



All our previous output on this subject can be seen at this weblink:



Declared interests

None received.

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