On November 26, the World Health Organization designated the newly identified SARS-CoV-2 lineage B.1.1.529 with a whooping 32 mutations in the spike protein alone a variant of concern and named it ‘Omicron’, making it the 13th lineage to receive a Greek letter under its nomenclature system.

The Greek letter nomenclature of variants was introduced by the WHO in 2021 as a uniform system of naming variants of interest and concern. This nomenclature system unifies the different systems of nomenclature that have existed since the beginning of the COVID-19 pandemic. These largely include the scientific names assigned by GISAID, the largest open-access global database of genome sequences and related data of SARS-CoV-2, Nextstrain, which provides a phylogenetic context of the genome sequences available in the public domain, and Pango, a network of researchers for dynamically identifying and naming lineages of SARS-CoV-2.

Bypassing stages

With the designation of Omicron as a variant under monitoring and further as a vaariant of concern (VOC) within a short span of two days, the WHO bypassed the stage of initially designating it as a variant of interest (VOI), which is a significant departure from the precedence followed for other variants of concern in the past.

For context, while the designation of Delta took about six weeks from the reporting of the lineage to the Pango network to the designation of the lineage as a VOC, Omicron was designated within a week of detection of the lineage (B.1.1.529). Delta, in contrast, was first designated a VOI in April this year and was further upgraded to a VOC on May 11, taking into consideration the emerging evidence on the transmissibility, epidemiological correlations from India as well as experimental evidence from across the globe. Omicron, in contrast, was designated as a variant under monitoring on November 24 and was classified as a VOC two days later.

The rapid pace at which WHO designated Omicron a VOC was a decision that did not come out of haste but was based on concrete scientific evidence which came early from Africa, although further efforts for evaluating the variant shall continue to gain more evidence. The timely detection of Omicron is predominantly attributable to the routine genome sequencing efforts of Network for Genomic Surveillance in South Africa (NGS-SA), an elaborate genomic and epidemiological surveillance network in South Africa comprising over 10 laboratories and academic institutions having a rich experience of having dealt with previous waves of COVID-19, including the detection of the VOC Beta late in 2020. The wider reach of sequencing technologies and open-access databases including GISAID and NCBI, which make genome sequencing data publicly available for research and interpretation, has also created a near real-time system for data generation, data sharing and interpretation. Along with these factors, the prompt detection of Omicron and many more new lineages in recent months is also attributed to the large number of researchers who collaborate online and sift through emerging genome sequences of the virus and keep a constant lookout for clusters of interest.

Three factors

Typically, a variant is designated a VOC if it has evidence that supports one of the three possible factors – increase in transmissibility or a detrimental change in COVID-19 epidemiology, increase in virulence or change in clinical disease presentation, or decrease in effectiveness of public health and social measures including vaccines, therapeutics and diagnostics.

The early evidence for Omicron suggested a detrimental change in COVID-19 epidemiology, along with possible increase in transmissibility and decreased effectiveness of vaccines. The detection of the variant epidemiologically coincided with an outbreak and a further uptick in the number of COVID-19 cases in Gauteng, South Africa, which was previously affected by the Delta wave and was expected to have high community immunity. There were multiple instances of fully vaccinated cases, including where a booster dose had been received. This suggested that the variant poses a higher risk of reinfection and vaccination breakthrough.

In contrast with the previous VOCs, a significant corpus of datasets having functional annotations of mutations in the virus based on evidence gathered from in-depth experiments from across the world is now available to help gain a deeper understanding of mutations in the context of transmission, immune escape and impact on current diagnostic tools and therapeutics.

Of the 32 mutations identified in the Spike protein, a significant large number were associated with immune escape, cell entry as well as better binding to the human receptor proteins. Early structural analysis was also suggestive of better binding to the host receptors, which provided added confidence in the preliminary assessments. The early reports of a number of Omicron cases from different countries in Europe also suggested that the variant was indeed spreading fast. Apart from this, scientific evidence gathered, lessons learnt and wisdom gained while dealing with the previously designated VOCs – Alpha, Beta, Gamma and Delta also helped in the assessment.

Convergence of evidence

The rapid designation of Omicron as a VOC is therefore the convergence of a number of factors, scientific evidence of all the above-mentioned factors. A cluster of genome sequencing originating from Botswana, South Africa, as well as a traveller from Hong Kong, all met the eyes of researchers in South Africa, which led to the designation of the cluster as the lineage B.1.1.529 by the Pango network.

While a part of the world prepares itself to combat the new variant with booster doses of vaccines and augmented healthcare preparedness, it is a grim reality that a large number in another part of the world are yet to receive their first dose of vaccine. The emergence of Omicron is thus a reminder that the virus will continue to evolve and prevail as long as a large part of the population lacks vaccines. The world should be reminded of the researchers in Africa, where under 7% of the population is currently vaccinated, who worked in not the best of infrastructure, funding and support systems that the world can offer, but have faithfully contributed to presenting with evidence that allows the world to be better prepared to handle the next wave.

It is thus a shame that the healthcare workers in Africa would have to grapple with an upcoming wave of infection without access to vaccines, therapeutics and support essential for combating the new variant. With the emergence of Omicron as a variant of concern, that we may lose many of our brave African frontline warriors, for want of vaccines to the very threat they helped alert the world should indeed be a concern.

(The authors are researchers at CSIR-IGIB, New Delhi.)