Since transmission begins before symptoms set in and the disease becomes severe, its characteristic is decoupled from disease
Since transmission begins before symptoms set in and the disease becomes severe, its characteristic is decoupled from disease
In early February, World Health Organization technical lead on Covid-19, Dr Maria Van Kerkhove, cautioned that the pandemic is far from over and new variants will emerge and such variants could be more transmissible than the Omicron BA.2 variant. “The next variant of concern will be more fit, and what we mean by that is it will be more transmissible because it will have to overtake what is currently circulating. The big question is whether or not future variants will be more or less severe,” Dr Van Kerkhove said.
Evading antibodies
The only way the next variant can become even more transmissible than the Omicron variant is by exhibiting a far higher ability to evade neutralising antibodies. This would mean that full vaccinations (two doses) will be even less effective in preventing breakthrough infections. But so far, fully vaccinated people have been found to be less likely to suffer from severe disease requiring hospitalisation and even death. That is because it is the T cells and B cells that come into play to reduce the severity of the disease. “The memory T cells are extremely unlikely to prevent SARS-CoV-2 infections. That is just not what T cells generally do. They may reduce COVID-19 disease severity and prevent deaths,” Dr. Shane Crotty from La Jolla Institute for Immunology, La Jolla, California, had earlier told The Hindu.
“The variants are a wild card. We still don’t know everything about this virus, we still don’t know everything about the variants and the future trajectory of that,” Dr. Van Kherkhove added.
Virulence unpredictable
While the next variant has to necessarily be more infectious than the Omicron variant, whether the variant will be more or less severe cannot be said with certainty. But it is important to remember that right from the very early stage of the pandemic, it became clear that transmission or virus spread begins even before symptoms can show up. That is what makes SARS-CoV-2 very different from the 2002 SARS virus and MERS virus. Since transmission begins even before symptoms set in and well before the disease becomes severe, the transmission characteristic is decoupled from disease. As a result, the natural evolution process selects variants not based on how they cause disease but how they can escape neutralising antibodies.
“Almost all [SARS-CoV-2] transmission happens while people have no or few symptoms, there is no particular reason for severity to play a role in evolutionary selection. NERVTAG [The New and Emerging Respiratory Virus Threats Advisory Group] thinks Omicron’s mildness is likely pure chance and the next one is likely to be more severe again,” Dr William P. Hanage from Harvard T.H. Chan School of Public Health, Boston, tweeted.
Immune escape
The virus was novel and none in the world had any immunity in the beginning of the pandemic. But with millions being infected by the virus and millions being fully vaccinated, and some with a combination of natural infection and vaccination, the next variant has to necessarily exhibit higher immune escape to cause infection. This is the reason that the next variant will exhibit more immune escape than the Omicron variant.
Even though the Omicron variant caused a large number of infections in virus-naïve people and in those who have been previously infected and vaccinated, at the population level, disease severity has been far less severe compared with the Delta variant. But lower disease severity was seen more in people who have pre-existing immunity either from vaccination or previous infection.
Two studies that tried to document the intrinsic disease severity of the Omicron variant compared it with the Delta variant. The studies found that the Omicron variant is about 75% as likely to cause severe disease or death as the delta variant. In a study posted as a preprint in medRxiv on January 12, this year, the authors conclude: “In the Omicron-driven wave, severe COVID-19 outcomes were reduced mostly due to protection conferred by prior infection and/or vaccination, but intrinsically reduced virulence may account for an approximately 25% reduced risk of severe hospitalization or death compared to Delta.”
Intrinsic severity
In the second study, a report by the Imperial College COVID-19 response team found 69% reduction in hospitalisation risk in people who have been reinfected compared with primary cases.
“This meaningful but fairly small difference implies that Omicron, Alpha, and wild-type SARS-CoV-2 have similar intrinsic severity,” Dr Roby P. Bhattacharyya from Massachusetts General Hospital, Boston and Dr William P. Hanage from Harvard T.H. Chan School of Public Health, Boston write in The New England Journal of Medicine.
“Viruses don’t inevitably evolve toward being less virulent; evolution simply selects those that excel at multiplying. In the case of COVID-19, in which the vast majority of transmission occurs before disease becomes severe, reduced severity may not be directly selected for at all,” Dr. Bhattacharyya and Dr. Hanage write. “Indeed, previous SARS-CoV-2 variants with enhanced transmissibility (e.g., Alpha and Delta) appear to have greater intrinsic severity than their immediate ancestors or the previously dominant variant.”
“It is also not true that variants are becoming milder. Delta was more severe than Alpha which was more severe than the original [virus]. Omicron is milder than Delta but likely not milder than original [virus]… and it’s not part of a steady progression to mildness.,” Dr. Hanage tweeted.
Separate lineages
Just like how transmission is decoupled from disease severity for the SARS-CoV-2 virus, it is also true that the new variants have not evolved from the existing ones. “Thus far, new variants of concern have not evolved from the dominant preceding one. Instead, they have emerged from separate lineages,” says a report in Nature. Dr. William Hanage, too, says the same in a tweet: “[SARS-CoV-2] evolves rapidly, but this isn’t straightforward. None of the main variants evolved from each other. Instead, so far they are all distinct, becoming gradually fitter via subvariants until replaced by an entirely new variant.”
