THE COVID-19 VARIANTS: A CAUSE FOR CONCERN
Suburban Diagnostics
Understanding COVID-19 mutations and consequences.
All viruses mutate, but the rate of mutation depends on the type of virus. RNA viruses mutate much faster than DNA viruses. The coronavirus is an RNA virus, just like the influenza virus. This ability to mutate quickly can confer the virus with enhanced virulence and evolvability.
The COVID-19 virus, constantly changes through mutations leading to new variants. There are 3 types of variants as designated by the CDC:
Variants of Interest (VOI)
Variants of Concern (VOC)
Variants of High Consequence (VOHC).
A variant of interest is one with mutations that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity. A variant of interest will require sequencing surveillance and epidemiological investigations to be further classified into a variant of concern.
A variant of concern is one for which there is evidence of an increase in transmissibility, more severe disease (increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.
A variant of high consequence is one in which there is clear evidence that prevention measures or medical countermeasures have significantly reduced effectiveness when compared to previously circulating variants. Luckily, no variant has, so far, qualified for the title of variant of high consequence.
Long suspected by many in the healthcare community, COVID-19 variants of concern have been detected in India & this has been confirmed in a press release by the Ministry of Health and Family Welfare (MoHFW).
There are 3 variants of concern which first detected in other countries that have arrived in India: the UK variant (aka B.1.1.7), the South African variant (aka B.1.351), the Brazilian variant (aka P.1). All 3 variants have increased transmissibility.
As of 15th April, the Indian SARS-CoV-2 Consortium on Genomics (INSACOG) had detected 1109 samples of the UK variant, 79 samples of the South African variant and 1 cases of the Brazilian variant amongst a total of 13,614 positive samples sequenced from 18 states of India.
A new “double mutation” variant has been detected and named “B.1.617”. It carries 2 mutations— E484Q and L452R in the crucial spike protein of the pathogen and was first identified in India. These mutations have both been seen in other variants, but were seen for the first time in this variant. These mutations have been associated with increased infectivity and immune escape. Immune escape is an ability acquired by the virus to evade anti-SARS-CoV-2 antibodies. As of 20th April, the variant has spread to 16 countries in total.
The B.1.618 variant (triple mutant variant), recently isolated from samples in West Bengal also has mutations which may confer it with increased infectivity and immune escape.
Another variant with N440K mutation (which has been associated with immune escape) has also been found in samples from Kerala, Andhra Pradesh and Telangana. However, recent data suggests that it is slowly being replaced by the B.1.617 and the B.1.1.7 variants.
Effect on RT PCR testing
In the case of new variants, it is a matter of concern that these mutations may affect the current RT-PCR test in identifying the virus. RT-PCR is able to detect the virus by detecting certain target sequences on the genome of the virus. RT-PCR assays that use multiple genetic targets for final results are less likely to be affected by genetic variants. This is because, it is highly unlikely that a virus will develop mutations in all the genetic targets of the assay. So, an assay which has multiple targets is unlikely to miss the virus.
For example, the B.1.1.7 UK variant has 2 deletions on the S-gene sequence, which has been seen to cause S-gene target failure in at least one RT-PCR assay. But even if the S gene is missed, the other gene targets in the assay will give positive results and so the final result will still be positive.
The fact that VOCs have been detected in India in such numbers which also coincides with the huge spike of cases that we have seen, should be a wake-up call for all of us. We need to be identifying these variants quickly. This can be achieved only by sequencing a significant percentage of positive samples. Public health precautions should also be stepped up dramatically if we are to overcome this latest obstacle that the pandemic has placed in our path.