Although Omicron’s impact on disease severity is still inconclusive, some early data points to a favourable trajectory
BY AMEEN KAMAL
We don’t yet know how much we should be concerned about Omicron, despite its classification as a Variant of Concern (VOC). There are opposite ends of the reaction spectrum with some experts expressing serious concerns, while others even expressed optimism.
Learning from dealing with uncertainties the past two years, it is worthwhile to err on the side of caution. However, based on current data, the most reasonable reaction may be somewhere in the middle, i.e., cautious yet optimistic.
It means people should maintain high standards of hygiene and physical distancing Standard Operating Procedures (SOPs), ensure sign-in and sign-out on the MySejahtera application (to assist in contact tracing), do frequent self-testing and reporting, and make healthier lifestyle choices.
The authorities would have to keep a close tab on our borders and increase sampling and viral genetic sequencing capacity alongside other efforts to ramp up immunological studies.
In others words, aside from increased public vigilance and authorities’ workload, the rest is the same – until and unless we have new and stronger evidence to react otherwise.
The disproportionate level of global panic has been driven by the unusually high numbers of mutations found in Omicron, with over 30 on the spike protein, while the Delta variant only has five spike mutations.
Given how much Delta has wreaked havoc globally, the fear is that these mutations could mean the virus to be more transmissible, evade the host immune system, and cause severe disease.
Because the mutations are mostly on the spike – which is the main target of antibodies generated through natural infection or vaccination – there are reasonable fears that the mutated spikes could result in the viruses not recognisable by antibodies and make the virus attach stronger to cells.
So, what do we know at the moment?
Recent sources appear to point to increased transmissibility and the likelihood of immune evasion causing re-infections. Although Omicron’s impact on disease severity is inconclusive, some early data points to a favourable trajectory.
What kind of disease severity?
In terms of transmissibility, a pre-print by researchers from the Michigan State University (MSU) estimated that Omicron could be 10 times more contagious than the original SARS-COV-2 or about 2.8 times as infectious as the Delta variant
A pre-print by South African researchers suggests that Omicron could be up to three times more likely to reinfect people, which is supported by the MSU researchers who estimated Omicron could have double the chance of escaping current vaccines than the Delta variant.
Note that these are pre-prints (not yet peer-reviewed), and their methodologies differ, meaning the findings, and what we can conclude from it, may change.
That said, it is plausible that many mutations in Omicron developed through intensifying selection pressures brought about by an increase in interventions such as through vaccines, naturally-induced immunity, and other drugs and biologics. If so, immunity evasion by Omicron is likely.
Thus, it would appear that sources mostly point to increased infectivity and higher chances of re-infections. But the most important question is, what kind of disease severity are we looking at?
A threat assessment report by the European Centre for Disease Prevention and Control (ECDC) dated Dec 2 mentioned that “Among the cases reported in the EU/EEA (European Union and European Economic Area) for which there is the available information on disease severity, half of the cases were asymptomatic and the other half presented with mild symptoms. No cases with severe disease, hospitalisations or deaths have been reported among these cases”.
But because the number of confirmed cases reported was only 70 in the EU/EEA, the ECDC noted that more data would be needed to draw conclusions. For example, indications of severe cases (through increased hospitalisation rates, etc.) may take a while to manifest at the population level.
Also, the cases reported by the ECDC have thus far involved more vaccinated younger age groups and travellers, which can be assumed as being generally “healthier” people. We know that younger age groups are less likely to show severe symptoms than older age groups.
Either way, it does sound promising, and it is not strange if Omicron is indeed causing less severe symptoms.
Many variables to consider
Firstly, more mutations do not necessarily mean a bad thing. Random mutations in viruses happen all the time, but selection pressures likely increase the chances that favourable mutations (to the virus’s survival) are retained and accumulated.
What kinds of characteristics would be favourable to the virus? To spread better, avoid detection by host immunity, and keep the hosts alive.
Becoming more infectious but less lethal to the infected person is a favourable characteristic for the virus, and thus, it has always been a potential evolutionary pathway.
As reported by Reuters, there are theories of Omicron originating through an immunocompromised (such as a HIV patient) individual in southern Africa, which could indicate that the virus has adapted to become less lethal to the host.
In other words, Omicron may have “learned” to be less severe.
If these hypotheses are true, Omicron pushing aside Delta to become the dominant variant could be a good thing. Under this scenario, more and more people would get infected, but few would get severe symptoms.
Furthermore, Omicron’s high number of mutations may even leapfrog our immune system to a new starting point that helps the body’s immune system to develop a defence against future infections and even future variants. This is why some reports have even posited how Omicron could be our “way out” of the pandemic, providing hope of truly “living with the virus” as we have always been with the common seasonal flu.
However, empirically answering these questions and testing these promising theories via robust tests and experiments will take some time.
As mentioned by MSU scientists, there are many variables: differences in individuals (underlying health conditions, race, gender, age) and vaccine types could result in varying sets of antibodies. Additionally, the inability to control all variables may limit the reliability of the population-level statistical analysis.
This is why the Health Director-General Tan Sri Dr Noor Hisham Abdullah mentioned that much is still unknown about this variant and advised Malaysians not to panic and continue adhering to protocols.
Need for increased post-immunisation surveillance capacities
The Centers for Disease Control and Prevention says that a VoC is “a variant for which there is evidence of an increase in transmissibility, more severe disease (for example, increased hospitalisations or deaths), a significant reduction in neutralisation by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.”
According to these criteria, there isn’t enough evidence at the moment to conclusively check all the boxes.
Aligned with WHO recommendations, we re-emphasise again the need for increased post-immunisation surveillance capacities, including genome analysis and serological studies to be increased significantly. The previously targeted one per cent of cases is not intense enough. The public also needs to adhere to public health measures to reduce virus circulation.
As being shown now with Omicron’s emergence, this is important for detection, supporting global research and understanding immunological uncertainties.
For the detection of Omicron, one suggestion for the authorities to consider is the use of PCR tests kits that target both stable and less stable parts of the virus, whereby Omicron is likely to yield negative results for the less stable part given its highly mutated spikes. Thus, given the current prevalence of Delta (making its positive predictive value strong), samples sent for genetic sampling for confirmation of Omicron may have a higher chance of successful detection.
In the meantime, we again urge vaccine developers to embark urgently on redesigning vaccines beyond inducing systemic immunity and mucosal immunity. This is a respiratory virus with highly mutational spikes. It makes sense to focus immunity on the respiratory system and counter the high mutation rate.
As for other researchers, we urge the study to understand not only what genetic sequences of the virus contribute to the severity of disease, but more importantly, what genetic sequences, markers, and predispositions of the individual would confer higher chances of severe disease.
If indeed Omicron is our way out, then the next step should be tailored interventions to address the relatively few people that do get the severe disease. — The Health
Ameen Kamal is the Head of Science & Technology at EMIR Research, an independent think tank focused on strategic policy recommendations based on rigorous research.
