The emergence and limited spread of the Mu SARS-CoV-2 variant

A recent report posted to the medRxiv* preprint server provides insights into the restricted worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mu (B.1.621) variant.

Background

SARS-CoV-2 emerged in late 2019 and caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. The pattern of the COVID-19 pandemic is continued to be remodeled by the subsequent emergence of SARS-CoV-2 variants of concern (VOCs). By late 2021, 13 SARS-CoV-2 variants of public health implications were discovered by the World Health Organization (WHO). While highly transmissible Delta and Alpha VOCs gradually became prominent in many regions of the globe, those with immune evasion capacities like the Mu VOC had a lesser influence. 

The Omicron VOC that emerged in late 2021 exhibited both high transmission and immune evasion capabilities and shortly became the dominant SARS-CoV-2 strain in many nations. Nevertheless, it is unclear why few SARS-CoV-2 VOCs, such as Omicron, have become globally dominant while the spread of other VOCs like Mu has been limited.

About the study

In the present study, the scientists evaluated the emergence and spread of SARS-CoV-2 Mu VOC, which was initially discovered in Colombia at the end of 2020, by adopting a multidisciplinary strategy. The authors combined genomic and experimental data to analyze the remarkably restricted transmission of the highly immune evasive Mu VOC.

The researchers initially evaluated the biological properties of Mu compared to other SARS-CoV-2 variants (Delta, Lambda, Alpha, Omicron, Beta, and Gamma) by employing replication and neutralization assays. Subsequently, the authors conducted a phylogenetic analysis of the Mu VOC to determine when B.1.621 and its sublineages probably emerged and when they were discovered. The team also performed genomic analyses of Mu. The researchers adopted an epidemiological strategy to evaluate the global spread and distribution of the Mu VOC. Finally, the team conducted a discrete phylogenetic inference to quantify the rate of inter-continental spread of Mu.

Results and discussions

The study results showed that the SARS-CoV-2 Mu VOC was more resistant to neutralization than the viral VOCs such as Delta and Alpha. Additionally, a hiked replication rate was not observed in any of the SARS-CoV-2 VOCs analyzed. 

The findings indicate that the immune evasion capacity of the Mu VOC was not solely adequate to outcompete other SARS-CoV-2 VOCs circulating globally during the second year of the COVID-19 pandemic. These data suggest that a higher transmissibility capacity was more advantageous than immune evasion during the second year of the SARS-CoV-2 pandemic. In addition, the later emergence of the worldwide dominant Omicron VOC, which was both highly immune evasive and transmissible, suggests that these qualities worked in concert to raise the Omicron infection rates to previously unheard-of levels over the world.

The phylogenetic analysis of Mu indicated that a delay occurred between the putative emergence of Mu and its initial detection in South America. The genomic evaluation of Mu suggested that a frameshift mutation generating a premature stop codon in ORF3a might have postponed publishing the B.1.621 clade genome sequences on the public repository global initiative on sharing all influenza data (GISAID).

The discrete phylogenetic inference revealed that despite the immune evasion characteristics and lengthy duration of undetected transmission of B.1.621 and its sublineages, Mu did not spread much beyond South America, contrary to the authors' predictions. Mu had spread from South to North America, Europe, and Asia unidirectionally. However, this might not be followed for future SARS-CoV-2 variants, necessitating a more detailed examination of viral circulation dynamics. 

Conclusions

The study findings illustrated that even though the SARS-CoV-2 Mu VOC was less susceptible to neutralization than the viral variants that emerged previously, Mu did not transmit substantially outside Central and South America. Furthermore, the findings depicted that the response of the worldwide genomic monitoring system to the Mu VOC was hampered by reporting gaps and delays.

The current study provides a comprehensive evaluation of the SARS-CoV-2 VOC, Mu. This multidisciplinary work implies that the immune escape of Mu itself was not enough to surpass the highly transmissible SARS-CoV-2 variants such as Omicron circulating in parallel with the Mu VOC.

The authors demonstrated the genomic underpinnings of SARS-CoV-2's viral fitness using known circulating SARS-CoV-2 genomes. Further, the study suggests that the knowledge of the intricate association between epidemiological and genomic features of prior SARS-CoV-2 variants should influence the strategies to manage the variants that are expected to emerge in the future.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.