Novel mutations in Covid 19 genome and its impact on healthcare management

RNA viruses are characterized by a higher rate of mutation than their hosts. The SARS CoV 2 is no exception. Most viral mutations have little to no impact on the virus’s infectivity. But depending on where the changes are located in the viral genome, they may affect a virus’s properties, such as transmission or severity. On an evolutionary basis, mutation contributes to viral genetic variability and fine tune the viral adaptation with the environment in a trial and error method where the fittest variant becomes triumphant. Currently, multiple variants of the virus that causes COVID-19 are circulating globally. Centre for disease control and prevention (CDC) established 3 classes for the SARS-CoV-2 variants: Variant of Interest (VOI), Variant of Concern (VOC), and Variant of High Consequence (VOHC).All VOI share a critical mutation called D614G. This mutant occurred in early phase of the pandemic in Europe and quickly became predominant implying enhanced transmission than the original virus. At least two research groups independently noted that D614G mutation correlated with increased viral loads in COVID-patients implying more serious disease. But as this D614G change is also associated with three or four other mutations, the role of the D614G mutation in these observations remained elusive. In August and September 2020, a SARS-CoV-2 variant named “ Cluster 5” variant was identified in Denmark. Preliminary studies have shown that this variant may result in reduced virus neutralization by antibodies in humans, which means potentially less immunity following natural infection or vaccination. In December 2020, the UK reported the presence of a variant of concern called SARS-CoV-2 VOC 202012/01 (Variant of Concern, year 2020, month 12, variant 01) with 23 nucleotide substitutions with a critical mutation (N501Y). Although preliminary results shows its increased transmission in human, it does not show any change in disease severity (as measured by length of hospitalization and 28-day case fatality), or occurrence of reinfection compared to other SARS-CoV-2 viruses. Another of the mutations in the VOC 202012/01 variant, which has a deletion was found to affect the performance of some diagnostic PCR assays. Nevertheless, most PCR assays use multiple targets and therefore the impact of the variant on diagnostics is not anticipated to be significant. However, more recent studies do indicate that there is a realistic possibility of increased risk of death in patients infected with this particular variant. On the other hand the South African variant or B.1.351 lineage is being reported to be associated with higher viral load and increased transmission. Moreover, this variant harbors ‘escape mutation' which might make the virus less susceptible to immune response triggered by vaccine. Most vaccines including Johnson & Johnson, Oxford, Sputnik V, Moderna, Pfizer have shown reduced efficacy against this variant. Brazilian variant or P1 lineage also shown to possess greater transmissibility, potential to reinfect and also share the most feared ‘ escape mutation'. California or west coast variant also shown to possess greater transmissibility than the original virus. The B.1.617, also known as the VUI ( variant under investigation) -21 APR-1 or the Indian variant is thought to be responsible for the recent surge in Covid cases in India. This variant has 13 mutations with 2 critical mutations, E484Q and L452R. These mutations, when taken individually, are not unique to the variant; rather, their simultaneous occurrence is. This variant has been shown to have enhanced infectivity and ability to evade immune response as well. ICMR reported that the Bharat biotech Covaxin can neutralize this strain albeit with a lower efficacy.The much discussed triple mutant of India is a misnomer as this variant has many mutations. Among these it has 3 important mutations which might cause it to become more transmissible. No proof of less susceptibility to vaccines has been found though.The SARS CoV 2 is an entirely new human pathogen and its evolution in human populations is hard to predict. New variants are continuously emerging on which mankind has absolutely no control. To maximally protect public health, what we can do is to track the new mutations and understand the consequences of these mutations on disease severity, transmissibility and vulnerability to vaccine induced immunity.

PRIYANKA BHOWMIK, PhD

Assistant professor, Department of Microbiology

Techno India University, West Bengal