Could the Omicron variant be the last variant of concern of the COVID-19 pandemic? Global immunity is key

Abstract

The Omicron variant was designated a Variant of Concern (VoC) due to its increased transmissibility and antibody evasion. Data from several countries however suggested a milder clinical outcome for the Omicron variant compared to the previous VoCs. The clinical outcome in the coming year (2023) is however uncertain due to Omicron’s persistent evolution, developing variants with increased immune escape attributes in the presence of populations that may not possess adequate immunological defences.

The Omicron variant utilizes the endosomal route of cell entry unlike previous VoCs. This may be due to Omicron’s superior spike protein receptor binding domain (RBD)’s adhesion to the host cell’s angiotensin converting enzyme II (ACE2) receptor. Efficient cell entry may have increased Omicron’s tropism to rapidly infect the extensive surface area of the nasopharyngeal mucosa and its adjacent sinuses. The endocytic mode of cell invasion may result in a more efficient recruitment of several contemporaneous RBD-ACE2 complexes of the same virus and other viruses to the attached host cell, suggesting a correlation between viralhost cell binding and transmissibility and a negative correlation with clinical severity. The nasopharyngeal region acting as a buffer, would have gained time with the initial containment of the Omicron infection providing immunological protection, preceding significant seeding into the lungs.

The combination of previous waves of natural infection, uneven global vaccination efforts and widespread Omicron infection and its most recent sub-variants (BF7 and XXB), may elude worldwide immunity, exacerbating the pathogenic effects of future SARS-CoV-2 outbreaks. Emulating the pattern of waves of infection during the devastating 1918 Spanish influenza, the current COVID-19 Pandemic may have approached an upended immunological equilibrium, due to adverse immunological, anthropogenic and environmental factors, swaying in favour of a more virulent subvariants.