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Journal of Medical Virology

The most recent identification of the Omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has added fuel to the close to 2-years' seemingly eternal flame of the global coronavirus disease 2019 (COVID-19) pandemic.1 Omicron was first identified in Botswana earlier in November. It was reported to World Health Organization (WHO) from South Africa on November 24, 2021, which was designated as a variant of concern (VOC) on November 26, 2021.1 Omicron contains a large number of mutations that were previously reported in other VOCs including at least 32 mutations in the spike protein alone compared to the 16 mutations in the already highly infectious delta variant, in addition to other proteins such as NSP12 and NSP14 that are essential for viral replication. The Omicron variant is thought to be at least three times more infectious than the original SARS-CoV-2 and possibly more so than the delta variant. The variant has so far been detected in at least 38 countries including Australia, Botswana, the European Union, Hong Kong, Israel, the United Kingdom, and the United States. At the time of writing this Editorial, a number of countries including Brazil, Canada, the European Union Indonesia, Iran, Israel, Maldives, New Zealand, Saudi Arabia, Singapore, Sri Lanka, Thailand, the United Kingdom, and the United States have implemented travel restrictions to eight southern African countries including Botswana, Eswatini, Lesotho, Malawi, Mozambique, Namibia, South Africa, and Zimbabwe where the Omicron was likely originated from while Israel bars entry to all foreign nationals. Some countries have issued partial lockdown and strict quarantine of the infected individuals. There are numerous urgent medical and scientific questions concerning the Omicron variant that need to be addressed. The first question is whether Omicron causes more severe disease and/or prolonged infections. While it is possible that the extensive mutations could render the virus less virulent, the chance is very small. In contrast, the highly infectious nature of this variant suggests that, once an individual is infected, there is likely wider and faster spread between cells, tissues, and organs, causing more severe tissue damages, hence more severe pathologies and disease manifestations. It is also possible that the variant causes a prolonged infection with inapparent symptoms and consequently confers virus spread to more people. The high infectious nature could be due to its robust replication fitness resulting in higher viral load and production of more variants. It is likely that more than one of these mechanisms might come into play. These clinical data should be available in the next few weeks. The second question is whether the mutations in viral Nsp12-RdRp and Nsp14-Exo confer a higher mutation rate seen in the Omicron variant. Through mutation and adaptation, viral variants can efficiently evade the host immunity, resulting in prolonged infection and virus spread to others. The third question is whether the current vaccines, which are entirely based on the original SARS-CoV-2 strain are protective against this new variant. This information could be quickly obtained by examining neutralization antibodies against an Omicron pseudovirus or an authentic infectious clone. It is noted that all four early Botswana Omicron variant patients were fully vaccinated, indicating a possible vaccine escape. However, we will likely not know whether the current vaccines are protective against severe disease until more clinical data are available. Regardless of the outcome, it seems prudent to immediately jumpstart the production of a vaccine against this new variant. In fact, numerous pharmaceutical companies have wasted no time and announced plans for developing vaccines against the new variant. Governments should join forces with vaccine companies to develop an efficient strategy to best deal with this rapidly emerging medical urgency. New variants of SARS-CoV-2 have been reported weekly if not daily. Poor public health infrastructure, lower vaccination rate, and presence of a large number of immunocompromised populations that have weaker immune protection and are more susceptible to infection could become the fertile ground for breeding new variants. Thus, a global concerted effort among the government agencies, pharmaceutical/biotech industries, and academic and healthcare institutions is required to efficiently contain this pandemic. The authors declare that there are no conflict of interests. Shou-Jiang Gao, Haitao Guo, and Guangxiang Luo conceived, wrote and revised the paper. Data are available from the corresponding author upon reasonable request.

Omicron variant (B.1.1.529) of SARS‐CoV‐2, a global urgent public health alert!