Recent SARS-CoV-2 variants such as BA.4 and BA.5 developed abilities missing from the first Omicron variants that allowed them to overcome humans’ innate immunity, revealed a study.Since the beginning of the Covid-19 pandemic, new variants of concern emerged independently from the first wave SARS-CoV-2 virus. Alpha, Delta and then Omicron in turn became the dominant variants in circulation.
The study, published in the journal Nature Microbiology, examined viral evolution in eight Omicron variants using cell models to better understand how the virus has reacted since the introduction of vaccinations.
Researchers at University College London (UCL) and the University of Glasgow in the UK found that the earliest Omicron variants, BA.1 and BA.2, were less able to overcome human innate immunity than Alpha or Delta.
But more recent Omicron variants, such as BA.5 and XBB, have relearned how to overcome human innate immunity and have done so in the same way as Alpha to Delta. This suggests a common evolutionary strategy that has implications for pathogen surveillance.
“We were surprised to find that early Omicron sub-variants were relatively bad at evading innate immunity compared to Alpha and Delta. This seemed like a backwards step in SARS-CoV-2 evolution and may explain reports of reduced disease severity when these variants were dominant.
Like Alpha to Delta, we found that the most recent Omicrons have increased the amount of innate immune antagonist proteins that they make, for example nucleocapsid and Orf6,” said Dr Ann-Kathrin Reuschl, from UCL Division of Infection & Immunity.
“The fact that later Omicron variants evolved in the same way as Alpha and Delta underlines how the innate immune system really is an effective gatekeeper for SARS-CoV-2 variant success,” Reuschl added.
To overcome innate immunity these later Omicron variants produce greater quantities of certain viral proteins, such as nucleocapsid and Orf6, that help to jam the cellular signalling pathways that triggers our antiviral response.
The findings help to explain why SARS-CoV-2 remains so capable of infecting people despite existing immunity from vaccines and prior infection. An effective way to avoid infection is to wear FFP3 masks or similar that can protect from virus breathed out by infected individuals.
“With SARS-CoV-2 we’ve had a unique opportunity to observe how a virus evolves to overcome our defences in real time, giving us an opportunity to predict what a virus with pandemic potential needs to do to be successful.
This may help us to assess the risk posed to humans by emerging viruses or new variants of existing viruses. It will be important to continue to monitor the virus as it continues to evolve,” said Professor Clare Jolly, from UCL Division of Infection & Immunity.