In a recent study published in PLoS ONE, researchers compared the mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant with others to highlight their evolutionary differences. In addition, the authors investigated animal-infecting SARS-CoV-2 variants.
Study: Mutations in SARS-CoV-2 are on the increase against the acquired immunity. Image Credit: Fit Ztudio/Shutterstock
Monovalent vaccines using adenoviruses or messenger ribonucleic acid (mRNA) have conferred significant protection against the coronavirus disease 2019 (COVID-19) pandemic in many countries. However, vaccine efficacy is lower against the highly mutated SARS-CoV-2 Omicron variant. Further, there are questions raised regarding Omicron origin, and it is believed that the increase in Omicron infections is because Omicron has mutated faster than the development of updated vaccines.
About the study
In the present study, researchers compared the mutations in the SARS-CoV-2 Omicron variant with others to highlight their evolutionary differences. In addition, the authors investigated animal-infecting variants.
Nucleotide (N) sequences were downloaded on December 27, 2021, (n=27,000) from the global initiative on sharing all influenza (GISAID) database. In addition, sequences from African regions were downloaded between July 1, 2021, and January 15, 2022. Only complete sequences containing <1,000 nucleotides were chosen for the analysis and characterized using principal component analysis (PCA) to evaluate sample characteristics based on sequence differences.
Each PCA axis presented N sequence differences at particular sites and multiple axes were used to study the evolutionary characteristics of SARS-CoV-2 variants. The results were compared with variants infecting animals to explore the possibility of developing a novel vaccine using weakened SARS-CoV-2 variants. The initial axis on human acclimatization was created with data until April 2020, across four independent groups, and was utilized for determining the origin of variants.
The other PCA axis considered for the analysis was derived utilizing two variants of concern (VOC) and variants of interest (VOI), from SARS-CoV-2 Alpha VOC to Omicron VOC. Omicron VOC with the highest mutations formed PC1 which was used to determine the variations in Omicron VOCs and the other variants that formed PC2. For characterizing the animal-infecting samples, two VOCs and 1500 samples were used. The team assessed vaccine effectiveness on the infected population residing in Japan and subsequently explored variant transition by PCA analysis.
Results
The fifth SARS-CoV-2 wave terminated after the initial and subsequent rounds of COVID-19 vaccinations; however, the sixth and most extensive pandemic occurred, in which some infected persons required hospitalizations although COVID-19 severity was lesser than expected. Large fluctuations were observed in the association between COVID-19 prevalence and COVID-19-associated mortality rates, reflecting SARS-CoV-2 variants’ lethality.
On evaluating PCA axes from data till April 2020 and comparing with recent axes data, variants appeared to be in three different groups and at that stage, SARS-CoV-2 acclimation to human beings appeared as complete. Sequences of animal-infecting variants belonging to the sequenced variant groups showed that transmission of some sub-forms of SARS-CoV-2 variants prevalent in deer, minks, cats, dogs, and zoo-based animals may have occurred from human beings as their origin was most likely to be from SARS-CoV-2 variants prevalent in regions where many cases of human infections were reported.
The currently dominant variants were found to have more amino acid substitutions (mutations). Variants of Omicron were distantly present from other SARS-CoV-2 variants. African samples recorded more cases of Omicron infections in the top right corner, indicative of higher infectivity of Omicron due to the presence of an insertion mutation in the SARS-CoV-2 spike (S) protein sequence comprising three amino acids.
One variant was found to cause one epidemic per region, with discontinuity in variant transition and the same causative SARS-CoV-2 variant was not detected in the SARS-CoV-2 epidemic which occurred in the following calendar year since individuals infected by that variant developed acquired immune responses against the variant without developing COVID-19. If a variant did not develop enough mutations for overwhelming the acquired immune responses, it could not cause SARS-CoV-2 epidemics again.
Omicron was initially detected in South Africa but variants of group 1, to which Omicron belonged, did not show prevalence in the country post-August 2020 and the C.1.2 variant of the same group was identified for a brief period during July 2021 and was distant from Omicron. The B.1.1.519 variant of the same group was closer to Omicron; however, the association between B.1.1.519 and Omicron remained unknown due to inadequate records. Omicron was highly mutated and its mutations neither showed resemblance with existing coronaviruses nor showed anything common with animal-infecting SARS-CoV-2 variants. Thus, the possibility of animal-to-human Omicron transmission was ruled out.
Animal-infecting variants rapidly mutated in animals and varied from human-infecting strains and the animal-adapted strains were not highly pathogenic to humans. Hence, they could be probably used as SARS-CoV-2 vaccines. Among animals, rapid acclimatization was observed. As an example, PC21 and PC25 mutations in the animal samples axis indicated acclimation to deer and minks in a few nations.
Animal viruses did not show the same concentration of nucleocapsid (N) protein and S protein mutations as human viruses. Variants which were distant from human variants, did not re-infect humans, as indicated by clustering of the human samples in the centre in PCA analysis, except for the variant detected in the Netherlands being prevalent in human beings. The variant was far from human viruses and even farther from mink viruses and hence, was probably detected due to mink acclimation.
Overall, the study findings showed that the Omicron VOC did not originate in South Africa and the parent of Omicron probably originated in regions that lacked sequence analysis and matured enough to overcome vaccination-acquired immunity and enter nations where sequence testing is performed. By the time Omicron was detected in South Africa, it had probably spread to other nations and the current pandemic could be the result of this delay. Given the increasing COVID-19 incidence in Japan, healthcare authorities must rely on measures other than vaccinations to curb SARS-CoV-2 transmission.
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