Science

Infection with Omicron variant of coronavirus may protect against influenza

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A new study by scientists at the University of Kent, UK, suggests that infection with the omicron (or BA.1) variant of SARS-CoV-2 may provide some form of protection against seasonal influenza. This option will lead to sustained production of interferons that will protect cells from superinfection caused by influenza A viruses.

The first case of the Omicron variant was detected on 9 November 2021 in Botswana; On November 26, 2021, the World Health Organization classified it as a variant of concern. The mutations it carries make it more infectious and more resistant to vaccine immunity; on the other hand, it is less likely to cause severe forms of COVID-19. It quickly gave rise to several sub-options (designated BA.2-BA.5) and we are currently seeing a significant spike in cases in France associated with sub-options BA.4 and BA.5, form BA5. be dominant.

The severity of the disease has been shown to be highly dependent on virus-induced interferon signaling. However, recent results in cell lines have shown that the BA.1 variant induces stronger interferon production than the Delta variant that preceded it. Therefore, a team of researchers set out to study the replication of the Delta, BA.1 and BA.5 viruses to compare interferon signaling in each case and to trace the effect of infection of one of its variants on the replication of the other. H1N1 virus.

More sustained response to interferons

Interferons are proteins naturally produced by cells of the immune system in response to the presence of a pathogenic agent in the body; they induce the production of proteins with antiviral (or antibacterial) action. Their name comes from the fact that they prevent the replication of the virus. There are three types of interferons: two come from virus-infected cells that secrete interferon molecules in small amounts to “warn” neighboring cells and thus prevent the virus from replicating; the third type is produced by lymphocytes.

As part of their study, the researchers first infected primary human bronchial epithelial cells and primary human monocytes with Delta and BA.1 viruses. Cells treated with a simple saline solution, free of viruses, served as a control sample. As expected, BA.1 showed faster replication kinetics than Delta in cell cultures. Similarly, BA.1 induced a stronger interferon response than Delta. “Interferon-α/β peaked 24 hours post-challenge, after which interferon-λ levels remained elevated until 120 hours post-challenge,” the study authors state in their preprint paper.

Short-term responses to type I interferon (α/β) elicit a protective antiviral response, while long-term activity of this interferon is associated with potentially harmful inflammation. In contrast, sustained responses to type III interferon (λ) suppress respiratory virus replication in airway epithelial barriers and prevent excessive inflammation, the team explains. Thus, the type I and III interferon responses observed here explain why Omicron appeared to be less pathogenic than other variants of SARS-CoV-2.

A variant that prevents influenza virus replication

The researchers then ran another experiment with the same cells; two days later, they infected them with the H1N1 virus, a subtype of the influenza A virus that is present in most cases of seasonal flu. The aim was to test whether the interferon response induced by BA.1 could induce an antiviral state preventing H1N1 replication.

Genomic RNA (left) or mRNA (right) levels of H1N1 influenza A virus (IAV) 24 hours after H1N1 infection. © D. Bozhkova et al.

A day later, they measured the H1N1 load in all cell groups. They then found that cells previously infected with the Delta variant, as well as control cells, had very high viral loads (nearly 10,000 times higher), suggesting that the H1N1 virus was replicating very quickly. In contrast, they did not observe an increase in viral load in cells infected with BA.1. “These results indicate that only BA.1, but not Delta, induces an interferon-mediated antiviral state in cultures. [cellulaires] which protects them from H1N1 infection,” the researchers conclude.

A similar experiment carried out with cells infected with the BA.5 variant showed similar interferon responses causing the same effect: both Omicron subvariants suppressed the replication of the H1N1 virus.

These results fully reflect the infection rate seen during the pandemic. “In England, delta infections and flu-like illnesses have increased since all restrictions were lifted on July 19, 2021. However, when the BA.1 variant became the dominant variant, the number of ILIs dropped sharply and has not increased since,” the researchers note in their paper. Note that these patterns could also be due to the fact that today people are more careful and protect themselves from winter infections.

A better understanding of how different variants of SARS-CoV-2 elicit different immune responses could help researchers more quickly determine the impact of potential new variants. But be careful, as the study authors note, these results in no way mean that intentionally getting COVID-19 is beneficial to protect yourself from the flu!

D. Boikova et al., bioRxiv.

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