Explained: Scientific Study Which Explains Why Omicron May Be Less Deadly Than Delta

On 26 November, the World Health Organization (WHO) named the new SARS-Cov-2 lineage B.1.1.529 as ‘Omicron’. It declared it as a 'variant under monitoring' on 24 November and as a 'variant of concern' (VOC) two days later which is unprecedented. Usually, a new lineage which has many concerning mutations is designated as a variant of interest (VOI) but this stage was bypassed in case of Omicron. Within a week of reporting of its lineage (B.1.1.529) to the Pango Network, it was declared a VOC. Pango is a network of researchers and is used for identifying and naming lineages of SARS-CoV-2.

To put this in perspective, Delta was declared as a VOI on 4 April and as a VOC on 11 May, after a gap of six weeks.

The data from countries which are witnessing exceptional surge in Covid-19 cases led by the Omicron wave despite high levels of vaccination proves that the WHO was right in its haste. South Africa, with 26 per cent of its population fully vaccinated, was hit the hardest. United Kingdom, with almost 70 per cent of population fully vaccinated and 35 per cent having received booster shots aka third dose, witnessed its biggest ever daily case peak a couple of days back with no sign of the wave relenting. The United States, where more than 60 per cent of the population is fully vaccinated and 16 per cent protected with booster doses, is being hit by fifth wave with almost 150,000 cases.

However, the silver lining from the available evidence so far suggests that Omicron may be less severe than Delta and other variants. The data from Gauteng, which houses quarter of South Africa’s population and was worst hit in the Omicron wave which now appears to be plateauing, offers this optimistic perspective. South Africa also has low levels of vaccine induced immunity (26 per cent of population with two doses), however natural immunity due to infections in previous waves is estimated to be high.

As one can see in the graph in the tweet above, while number of cases and test positivity peaks are approaching the levels during Delta wave, hospitalisations are half of the peak level and deaths only one-tenth (though they haven’t peaked yet). Even if death metric doubles to 20 per cent before flattening, this would mean one-fifth less deaths. Of course, part of it could be attributed to existing immunity but certainly the lesser level of severity of Omicron itself (especially in light of much faster rate of infections) may also be playing a key role.

The issue of much higher transmissibility (thanks to 36 mutations in the spike protein itself) but less severity was confounding many, especially the laymen who are not into the nuts and bolts of science of viruses. To nail the actual reason, a group of scientists carried out a study that offers some clues about this unique feature of Omicron.

The study (pre-print release; undergoing peer review) is by researchers from the Li Ka Shing Faculty of Medicine at the University of Hong Kong (HKUMed). It strives to explain how Omicron infects human respiratory tract.

The research team led by Dr Michael Chan Chi-wai, Associate Professor, School of Public Health, HKUMed found that Omicron infects and multiplies 70 times faster than the Delta variant and original Wuhan virus in human bronchus (which explains why Omicron spreads so fast) but infection in the lung is significantly lower than the original SARS-CoV-2 (which explains lower disease severity).

The researchers at HKUMed employed the technique of using ex vivo cultures of the respiratory tract for their investigation where lung tissue removed for treatment of the lung was used to create an experimental model on which behaviour of different variants was observed.

“At 24 hours after infection, the Omicron variant replicated around 70 times higher than the Delta variant and the original SARS-CoV-2 virus. In contrast, the Omicron variant replicated less efficiently (more than 10 times lower) in the human lung tissue than the original SARS-CoV-2 virus, which may suggest lower severity of disease,” the researchers found.

However, Dr. Chan issued two important caveats that ‘the severity of disease in humans is not determined only by virus replication but also by the host immune response to the infection, which may lead to dysregulation of the innate immune system, ie 'cytokine storm' and "by infecting many more people, a very infectious virus may cause more severe disease and death even though the virus itself may be less pathogenic".

Dr Robert W Malone, credited with inventing mRNA vaccines and RNA as a drug, certainly paints an optimistic scenario. “What if what has really happened is that Omicron has evolved to change the location where it replicates in our body? What if it has evolved to replicate more in our upper respiratory airway, and less in the deep part of our lung tissues?

"Has anything like that ever happened before, perhaps with other respiratory RNA viruses? Like, say, influenza A? Absolutely yes. In general, more severe pandemic influenza strains are often associated with receptor binding mutations that enable them to infect deeper lung tissues, while influenza strains that cause less disease infect upper parts of our respiratory tract. However, viruses that generally infect deep lung may be less infectious to others," he writes.

Dr Malone says that the study by Hong Kong University is significant because it indicates that "what may be most important about Omicron may not be the ability to evade vaccine-induced immunity, but that it has shifted its preferred tissue target for infection and replication to the upper airway instead of deep lung. That could explain why it is more infectious, replicates to higher levels, and yet causes less severe disease."

These can perhaps give important clues to authorities on how to proceed as they prepare for Omicron. Given the speed of spread of Omicron, stopping it with masks, social distancing, etc, will only take us so far. And while Delta wave may have taken the need for oxygen to unprecedented levels, that may not be the case with Omicron. For this, early treatment will be key so that the disease is not allowed to worsen and people can get better quick, preferably at home. Omicron is a different beast and it would have to be dealt strategically, perhaps with a tweaked public health toolkit.