The SARS-CoV-2 virus has undergone several mutations since it was first identified as the causative agent for Covid-19. Till date, the World Health Organization (WHO) has identified four variants of concern (VOC) namely alpha (B.1.1.7), beta (B.1.351), gamma (P.1) and delta (B.1.617.2). It has also identified two variants of interest (VOI) viz. lambda (C.37) and Mu (B.1.621).

Mu is the latest SARS-CoV-2 variant to be designated as a VOI and was added to the list on August 30, 2021. The Mu variant was first detected in Colombia in January 2021, where it became the key driver of the pandemic overtaking the till then prevailing gamma strain. It has since then been found in at least 50 countries. The mutations in the mu variant (T95I, YY144-145TSN, R346K, E484K, N501Y, D614G, P681H, D950N) allow potential immune escape. The E484K mutation in particular, which is also found in the beta and gamma variants, has shown the greatest reduction in neutralization by  antibodies produced after natural SARS-CoV-2 infection and Covid vaccination.

The mu variant has shown a marked resistance to antibodies generated due to natural infection in addition to the antibodies generated after Covid vaccination in a new NEJM study.¹

For the study, the researchers generated pseudoviruses bearing the spike protein of the mu variant or the spike protein of other VOC or VOI. Then virus neutralization assays were done on serum samples from Covid patients and persons who had taken the Pfizer-BioNTech (BNT162b2) vaccine.

Serum samples were obtained from 13 persons who had been infected in the early days of the pandemic during April through September 2020 and had recovered from Covid. On neutralization assays, the mu variant was 10.6 times more resistant to neutralization compared to the parental B.1 lineage bearing the D614G mutation. Similarly, the mu variant was found to be 9.1 times as resistant as the parental virus in virus neutralization assays done on serum samples from 14 recipients of the Pfizer vaccine. When it was compared to the beta variant, the mu variant was 2.0 times more resistant to neutralization by convalescent serum and 1.5 times more resistant to neutralization by the serum of vaccinated individuals.

Breakthrough infections are being reported and majority of them are caused by VOCs. The delta variant, which is a highly transmissible variant, was the key driver of breakthrough infections during the second wave, which proved to be very deadly.

Today several vaccines are available for use, but no vaccine is 100% protective. Studies have also shown waning of antibody levels after vaccination. Hence, breakthrough infections are a cause for concern, especially with the new emerging SARS-CoV-2 variants. The CDC has approved a booster shot, but only for the immunocompromised persons, as of now. India is yet to decide on a booster dose.

Will the mu variant become a VOC? We cannot say at this point of time. However, the results of this study point out the need to monitor the mu variant and understand the risks better. Many parts of the world are facing a resurgence of Covid-19 cases. The WHO has warned that “Europe is back as the epicentre of the pandemic”. Though the situation seems to be stable in most parts of the country, the need to adhere to covid-appropriate behavior - masks (double masking), physical distancing, hand washing, avoiding crowds - continue to be as important now as they were before.

Reference

1. Uriu K, et al. Neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine serum. N Engl J Med. 2021 Nov 3. doi: 10.1056/NEJMc2114706.