Natural immunity from Omicron infection weak, limited, study finds

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Infection with the Omicron variant of SARS-CoV-2 provides little long-term immunity against other variants in unvaccinated people, according to a study published in the journal Nature.

In experiments using mice and blood samples from donors who were infected with Omicron, researchers at Gladstone Institutes and University of California, San Francisco (UCSF) in the US found that the Omicron variant induces only a weak immune response.

In vaccinated individuals, this response — while weak — helped strengthen overall protection against a variety of COVID-19 strains.

In those without prior vaccination, however, the immune response failed to confer broad, robust protection against other strains.

"In the unvaccinated population, an infection with Omicron might be roughly equivalent to getting one shot of a vaccine,” said Melanie Ott, director of the Gladstone Institute of Virology and co-senior author of the study.

"It confers a little bit of protection against COVID-19, but it’s not very broad,” Ott said in a statement.

"This research underscores the importance of staying current with your vaccinations, even if you have previously been infected with the Omicron variant, as you are still likely vulnerable to re-infection, said co-senior author Jennifer Doudna, a senior investigator at Gladstone, and professor at UC Berkeley.

As the Omicron variant of SARS-CoV-2 spread around the globe in late 2021 and early 2022, anecdotal evidence quickly mounted that it was causing less severe symptoms than Delta and other variants of concern.

However, scientists were not initially sure why that was, or how a weaker infection might impact long-term immunity against COVID-19.

"When the Omicron variant first emerged, a lot of people wondered whether it could essentially act as a vaccine for people who didn’t want to get vaccinated, eliciting a strong and broad-acting immune response,” said Irene Chen, co-first author of the study and graduate student in Ott’s lab.

The team of researchers first examined the effect of Omicron in mice. Compared to an ancestral strain of SARS-CoV-2 and the Delta variant, Omicron led to far fewer symptoms in the mice.

However, the virus was detected in airway cells, albeit at lower levels.

Similarly, Omicron was able to infect isolated human cells but replicated less than other variants.

The team then characterised the immune response generated by Omicron infections.

In mice infected with Omicron, despite the milder symptoms, the immune system still generated the T cells and antibodies typically seen in response to other viruses.

"We demonstrated in this study that the lower pathogenicity of Omicron is not because the virus cannot take hold, said Nadia Roan, an associate investigator at Gladstone. That leaves other reasons which might explain why Omicron differs from other variants in terms of symptoms and immunity, including the lower replication seen with Omicron or the types of antibodies that the immune system generates in response to the virus.

"To gauge how the immune response against Omicron fared over time, the researchers collected blood samples from mice infected with the ancestral, Delta, or Omicron variants of SARS-CoV-2 and measured the ability of their immune cells and antibodies to recognise five different viral variants — ancestral (WA1), Alpha, Beta, Delta, and Omicron.

Blood from uninfected animals was unable to neutralise any of the viruses — in other words, block the ability of any of the viruses to copy themselves.

Samples from WA1-infected animals could neutralise Alpha and, to a lesser degree, the Beta and Delta virus — but not Omicron, the researchers said.

Samples from Delta-infected mice could neutralise Delta, Alpha and, to a lesser degree, the Omicron and Beta virus, they said.

However, blood from Omicron-infected mice could only neutralise the Omicron variant.

The team confirmed these results using blood from ten unvaccinated people who had been infected with Omicron — their blood was not able to neutralise other variants.

When the researchers tested blood from 11 unvaccinated people who had been infected with Delta, the samples could neutralise Delta and, as had been seen in mice, the other variants to a lesser extent.

When they repeated the experiments with blood from vaccinated people, the results were different: vaccinated individuals with confirmed Omicron or Delta breakthrough infections all showed the ability to neutralise all the tested variants, conferring higher protection.

"When it comes to other variants that might evolve in the future, we can not predict exactly what would happen, but based on these results, I suspected that unvaccinated people who were infected with Omicron will have very little protection,” said Ott.

"But on the contrary, vaccinated individuals are likely to be more broadly protected against future variants, especially if they had a breakthrough infection, she said.