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Previous Covid-19 Infection May Not Protect Against Omicron – Expert Reaction

Press Release – Science Media Centre

Early research from South Africa suggests the Omicron variant may carry a higher reinfection risk compared to the Beta and Delta variants.

Researchers looked at the data of almost three million South Africans who were previously infected with Covid-19 to see whether the risk of getting reinfected has changed with the arrival of the Beta, Delta, and Omicron variants. They found the Omicron variant is linked with a “substantial ability” to evade the immunity built up from a prior infection, while there was no such evidence of the Beta or Delta variants doing so.

This research is a preprint and has not yet been formally peer reviewed.

The SMC asked experts to comment on the research.

Associate Professor Siouxsie Wiles, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, comments:

“Researchers in South Africa are doing an incredible job of trying to find out as much as they can about the new omicron variant as fast as possible and sharing it with the world. In this preprint, they’ve calculated the risk of reinfection of people who have previously had COVID-19 with this variant compared to the beta and delta variants that caused their second and third waves of disease.

“Their data suggests the risk of reinfection with omicron could be about three times higher than with beta and delta suggesting the constellation of mutations omicron possesses can help it evade our immune system.

“One confounding factor could be that the arrival of omicron may have coincided with people’s immunity waning after their previous infection. However, there is anecdotal evidence from other confirmed cases around the world that the omicron variant may more easily infect fully vaccinated people suggesting this increased risk of reinfection is real.

“What we don’t yet know is how well being vaccinated or having had COVID-19 is able to protect people from having severe disease after infection with the omicron variant. This is something it will take a few weeks to months to find out.”

No conflict of interest.

Professor Nigel French, Co-Director, One Health Aotearoa, comments:

“This is an important analysis of the available data from South Africa that provides evidence of immune escape associated with Omicron, which wasn’t evident for previous Beta and Delta variants. The authors use two approaches that come to the same conclusion and, if this were supported by ongoing experimental virus neutralisation studies, this would have major implications for global spread of the new variant. It would mean Omicron could reinfect previously infected individuals at a higher rate than previous variants of concern. There are limitations to the study acknowledged by the authors, mostly related to missing data and potential misclassification of individuals as at risk of primary or reinfection during certain periods, as well as the absence of data related to vaccination status.

“Concerning vaccination, the authors conclude that ‘increasing vaccination uptake may reduce the risks of both primary infection and reinfection’. This is important – it is still likely that two, and to a greater extent, three vaccinations (i.e., a booster) will reduce the risk associated with Omicron, compared to no vaccination. Further, we still don’t know whether this variant is associated with milder or more severe disease, so there is still much to learn.

“The study shows the importance of having high quality surveillance data that is made available for rapid epidemiological analyses.”

No conflict of interest.

Professor Michael Plank, Te Pūnaha Matatini and University of Canterbury, comments:

“This study shows that the risk of being re-infected with Covid has risen sharply in South Africa in recent weeks. At the moment, this is correlation rather than causation because the researchers didn’t have direct data on the variants involved. But nevertheless, it suggests that the omicron variant is better able to evade immunity and infect people who have had Covid previously. This is consistent with expectations based on the type of mutations omicron has.

“There is still a lot we don’t know yet about the omicron variant, including how well existing vaccines will work and whether it causes more severe disease or less. However, the early signs are concerning. New Zealand is in a good position to keep this variant out in the short-term because we still have our MIQ system. Vaccine manufacturers are confident they will be able to update vaccines for the omicron variant if needed, but this will take time. It would be prudent to maintain border settings designed to minimise the risk of importing omicron until more is known.”

Conflict of interest statement: Michael Plank is partly funded by the Department of Prime Minister and Cabinet for research on mathematical modelling of COVID-19.

Dr Matthew Hobbs, Co-Director, GeoHealth Laboratory, and Senior Lecturer in Public Health, School of Health Sciences, University of Canterbury, comments:

“Researchers in South Africa should be highly commended for the work they are doing. This study compares the risk of reinfection for people who have already had COVID-19 for the omicron variant. Risk of reinfection with omicron was estimated to be around three times higher. This is concerning as it suggests the various mutations around the spike protein that omicron has may help it get around our own immune system response.

“We still don’t know whether omicron is associated with milder or more severe disease. We also don’t know other things like how well being vaccinated is able to protect people from having severe disease after infection with omicron. However, this important evidence will emerge over the next few weeks. This study begins to piece together parts of the puzzle and perhaps confirms some of our suspicions around the heavily mutated omicron variant.”

No conflicts of interest declared.

Dr Dianne Sika-Paotonu, Immunologist, Associate Dean (Pacific), Head of University of Otago Wellington Pacific Office, and Senior Lecturer, Pathology & Molecular Medicine, University of Otago Wellington, comments:

“The recently emerged Omicron variant of the SARS CoV-2 virus classified by the WHO as a variant of concern, has already been identified in a number of different countries including Australia.

“The emergence of new variants sadly highlights some of the major inequities affecting countries associated with COVID-19 vaccine accessibility and the vaccination roll-out globally.

“Data released on 2nd December 2021 from a pre-print study involving 2,796,982 individuals from South Africa who’d previously tested positive for COVID-19, showed that of this number 35,670 persons had become reinfected with the SARS-CoV-2 virus.

“When compared with the original strain affecting South Africa, the authors of this work found no increased risk of reinfection was associated with either the Beta or Delta variants of the SARS-CoV-2 virus, however the risk of reinfection with Omicron was more than two times higher. This strongly suggests the Omicron variant is able to evade immunity, generated by previous infection.

“What is yet to yet determined however, is whether Omicron can overcome vaccine induced immunity, and whether or not Omicron leads to more severe illness, hospitalisation and death when compared to other variants. It’s important to note also that information is still needed to understand how protective the current COVID-19 vaccines are against the Omicron variant.

“Although Omicron hasn’t reached Aotearoa New Zealand yet, a maintained focus on vaccination, border controls and public health settings will be needed moving forward.

“In Aotearoa New Zealand, we’re continuing to experience the impact of the Delta variant on day 1 after movement into the new COVID-19 Protection Framework, or Traffic Light System. Lower COVID-19 case numbers are being reported in the Auckland Region, with growing case numbers outside the Auckland Region and across the country – and including in the South Island. There are currently 79 people in hospital, with nine people in ICU or HDU, with wastewater detection results indicating the SARS-CoV-2 virus is being picked up in Matamata and Gisborne.

“COVID-19 vaccination levels within Aotearoa New Zealand continue to increase with 93 per cent for first doses and 87 per cent full doses being reported. It was also encouraging to note vaccination rates in Northland have increased to 86 per cent for first doses, a testament to all the hard work being undertaken with targeted and tailored equity approaches especially with Māori-led efforts to address COVID-19 vaccine accessibility issues that have persisted.

“We all still have work to do to keep others safe from COVID-19. Please get vaccinated and tested, and reach out to help others do the same.”

No conflict of interest.

Professor Peter McIntyre, Medical Advisor, Immunisation Advisory Centre, comments:

“This is an enormously impressive study both for the size and quality of the SARS-CoV-2 infection databases maintained in South Africa and the speed with which it was produced. It confirms what was suspected – that Omicron is better able to reinfect previously infected people than was the case with Delta, consistent with it having three-fold more mutation sites, many of which were associated with presumptive immune evasion.

“However, interpretation of what this means at the population level is much more uncertain, especially with respect to the key question – to what extent is protection against severe disease (hospitalisation or death) preserved despite increased susceptibility to infection? We also do not know how many of the cases of identified re-infection occurred in people who had also received vaccine versus those who only had previous infection. This will be strongly linked to age in South Africa as – although overall vaccine coverage might only be around 25 per cent – in persons over 60 years it is close to 70 per cent. It would be important to know if re-infection risk was different in people with hybrid immunity (vaccine post infection) vs infection only or vaccine only.

“This is, however, difficult to know as in South Africa as opposed to New Zealand, where the intensity of testing is extreme, lots of people will have had infection that was not identified through testing. Serological studies have shown that it is likely that at least 70 per cent and probably a much higher percentage of the population in South Africa have been previously infected but have not been tested. It is also important to point out that despite a higher relative number of re-infections, primary infections (those with no record of previous infection) are much more numerous in their data. Although the authors do not highlight this, it is notable to me that the relative proportion of re-infections also looked high in Jan 2021 when Beta – which also had immune escape characteristics – was dominant in South Africa.

“The bottom line is that irrespective of the variant, people who are neither previously infected nor previously vaccinated are at by far the highest risk of severe disease. It may not be a problem at all to be re-infected by a new variant if you are previously infected (booster by infection rather than vaccine) as long getting a re-infection or an infection post two vaccine doses does not make you more than ‘influenza-like illness’ sick – i.e., not needing oxygen, to go to hospital, etc.

“There is now a lot of evidence that the people who have the best protection against infection or severe illness when a new variant comes along are those who have hybrid immunity due to infection then vaccination or – now becoming more common overseas – vaccine and then later infection. Either way this is a lot more protective than infection-derived immunity on its own. Unless Omicron causes a situation where previously vaccinated people get very sick, it will not be a significant issue for highly vaccinated countries except for the old, the frail, the immune compromised, for whom we need boosters and then more boosters and also to have effective antivirals available.

“Do not panic – this is a coronavirus doing what it needs to do from its point of view, which is to be able to infect new people and replicate. The virus isn’t interested in making people sick and especially not in killing them as that reduces likelihood of being passed on, so I will be very surprised if Omicron leads to a problem with severe disease, unless you are unvaccinated, as we saw with Delta. And it’s still important to get those previously infected people in South Africa vaccinated because that gives much better protection. The good news is they probably only need one dose to have better protection than we in New Zealand have even with boosters, if not old and/or frail.”

No conflicts of interest declared. NOTE: The Immunisation Advisory Centre (IMAC) has a contract with the Ministry of Health to deliver education and training to the healthcare sector for COVID-19 vaccines.

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