Since the COVID-19 outbreak first began in late December 2019, the evolution of the causative agent SARS-CoV-2 has led to the emergence of four variants of concern including the alpha (B.1.1.7) lineage that first emerged in the UK and the beta (B.1.351), gamma (P.1) and delta (B.1.617.2) lineages that were identified in South Africa, Brazil and India, respectively. Five variants of interest have also emerged, including the Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C.37), and Mu (B.1.621) lineages discovered in Nigeria, New York, India, Peru, and Columbia, respectively. The most recently recognized of these variants is the Mu (B.1.621) lineage, which was classified as a new variant of interest by the WHO on August 30th. By this point, the lineage had been detected in 39 countries. In Colombia, where the variant was first isolated in January, a huge surge in COVID-19 occurred between March and August, with cases reaching a peak of 33,594 per day on June 26th.Although the P.1 (gamma) variant of concern was dominant during the initial phase of this surge, B.1.621 outcompeted P.1 and all other variants in May and has driven the epidemic in Colombia since then.

Researchers in Japan have warned that the Mu (B.1.621) variant appears to be highly resistant to neutralization by sera from convalescent or vaccinated individuals. The B.1.621 variant, first isolated in Colombia in January this year (2021), was classified as a variant of interest by the WHO on August 30th. The resistance that emergent variants have so far exhibited can be attributed to several mutations that have arisen in the viral spike protein – the primary structure involved in mediating the infection of host cells. The majority of B.1.621 variants harbor the following eight spike mutations: T95I, YY144-145TSN, R346K, E484K, N501Y, D614G, P681H, and D950N. Several of these mutations are commonly seen in variants of concern, including E484K (present in B.1.351 and P.1), N501Y and P681H (present in B.1.1.7), and D950N (present in B.1.617.2). Now, Dr. Kei Sato and colleagues have conducted a study showing that the variant was more resistant to neutralization by serum-mediated neutralization than all other variants of interest or concern that have been identified to date.

To assess the sensitivity of B.1.621 to neutralization by convalescent or vaccinated sera, Sato and colleagues generated and compared different pseudoviruses harboring the spike proteins of B.1.621 or the other variants of concern and interest. Virus neutralization assays revealed that B.1.621 was 12.4 times more resistant to sera taken from eight COVID-19 convalescents who were infected between April and September 2020 than the parental virus was. The variant was also 7.6 times more resistant to sera obtained from ten individuals who had been immunized with Pfizer-BioNTech’s BNT162b2 vaccine compared with the parental virus. A direct comparison of all the pseudoviruses revealed that B.1.621 was more resistant to serum-mediated neutralization than all of the other currently recognized variants of interest and concern. This includes the South African beta (B.1.351) lineage that had been recognized as the most resistant so far. In their research, scientists wrote that the Mu variant shows a pronounced resistance to antibodies elicited by natural SARS-CoV-2 infection and the BNT162b2 mRNA vaccine.

Since breakthrough infections are a major threat of newly emerging SARS-CoV-2 variants, they strongly suggest further characterizing and monitoring this genetic variant.

• Edited by Dr. Gianfrancesco Cormaci, PhD, specialista in Clinical Biochemistry.

Scientific references

Sato K et al. bioRxiv 2021 Sept 6:459005.

Shi P et al. bioRxiv 2021 Sept 2:458704.