New omicron subvariant BA.5 can efficiently infect lung cells, raising risk of severe disease

Omicron-derived virus variants currently dominate SARS-CoV-2 infections worldwide. Unlike earlier variants, omicron tends to result in fewer severe cases. This reduced severity is believed to be due to its lower efficiency in infecting lung cells, leading to less frequent pneumonia.

However, a significant development has emerged from an international team, including scientists from the German Primate Center—Leibniz Institute for Primate Research. They have identified a concerning mutation in the spike protein of the omicron subvariant BA.5. This mutation enables the virus to efficiently infect lung cells once again. Their findings, published in the prestigious journal Nature Communications, highlight that during the evolution of omicron subvariants, certain viruses may regain the ability to effectively spread in the lungs, potentially causing severe illness, especially in vulnerable individuals and those with insufficient immunity.

Omicron subvariants

During the first half of 2022, the BA.1 and BA.2 omicron subvariants were prevalent during the COVID-19 pandemic. Unlike previously circulating variants like delta, these omicron subvariants had a common feature: they were not particularly adept at infecting lung cells. However, there remained uncertainty about the omicron subvariant BA.5, which became dominant in autumn 2022, and whether it shared the same limited ability to infect lung cells.

To shed light on this matter, a team of scientists, led by Markus Hoffmann and Stefan Pöhlmann from the German Primate Center, conducted a study. Their findings have revealed that due to a mutation in the spike protein, BA.5 actually infects lung cells much more efficiently than the earlier omicron subvariants. This discovery could have significant implications for understanding the virus’s behavior and its potential impact on human health, especially for vulnerable individuals and those with weakened immunity.

Mutation in the spike protein

The researchers made a significant discovery concerning the spike protein of the omicron subvariant BA.5. They observed that in comparison to earlier subvariants, the spike protein in BA.5 undergoes more efficient cleavage. Moreover, BA.5’s spike protein facilitates the entry of the virus into lung cells and facilitates the fusion of lung cells more effectively.

To delve into the mechanisms of how the virus infiltrates lung cells, the scientists employed “pseudo-viruses,” a safe model system that mimics the behavior of the actual pathogen.

Markus Hoffmann, the lead author of the study, elaborated on their findings, stating, “We have identified a mutation in BA.5 that grants the virus the ability to penetrate lung cells with higher efficiency than the previously dominant omicron subvariants. This indicates that the continuous evolution of omicron subvariants may give rise to viruses in the future that can effectively spread within the lower respiratory tract, potentially leading to severe illness, particularly in individuals lacking sufficient immune protection.” The specific mutation responsible for these altered properties in omicron BA.5 is known as “H69Δ/V70Δ.” This discovery highlights the importance of monitoring viral mutations and understanding their potential implications for public health.

Confirmation with the real virus

To validate the findings obtained through laboratory experiments, Christian Drosten’s team at the Virology Department of Charité—Berlin University Hospital conducted further investigations. Their experiments with real viruses of the BA.5 strain confirmed that it indeed infects lung cells efficiently, supporting the results from Göttingen.

To determine BA.5’s infectivity in living organisms, researchers at the University of Iowa in the U.S. compared the lung infections in mice that were exposed to BA.5 with those infected with other omicron subvariants. Astonishingly, BA.5 replicated up to 1,000 times more efficiently in the mice’s lungs than the earlier omicron subvariants.

Similarly, experiments with ferrets at the Friedrich-Loeffler-Institut in Greifswald—Insel Riems, Germany, provided further insight. They demonstrated that the BA.5 subvariant spreads more effectively in the upper respiratory tract compared to previous virus variants.

Stefan Pöhlmann, who leads the Infection Biology Unit at the German Primate Center, summarized the collective results, stating, “These findings suggest that, similar to other omicron subvariants, BA.5 is highly contagious and has also evolved the ability to efficiently infect lung cells.” He emphasized the importance of close monitoring of the ongoing evolution of omicron subvariants to rapidly identify any variants with increased risk potential. This vigilance is crucial for addressing potential public health challenges that may arise from these viral mutations.

Source: The German Primate Center

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