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SARS-COV-2: VARIANTS DETECTED IN INDIA

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SARS-COV-2 VARIANTS: WHAT WE KNOW SO FAR

Over the past few days, we have seen a slow creeping, yet worrying, rise in the number of COVID-19 cases reported per day in Mumbai. There could be many possible reasons for this:

• Many businesses have reopened and restarted working from the office

• There have also been an increased number of outdoor and indoor gatherings

• It is possible that people have started to be lax about precaution­s

• The last possibilit­y is that virus variants with increased transmissi­bility are starting to spread in India

WHAT IS A VARIANT?

The coronaviru­s has an RNA genome with -30,000 bases. As the virus spread across the world over the past year, it has undergone mutations. A new virus variant is one which has one or more mutations that differenti­ate it from the ‘wild-type’ or predominan­t virus variants already circulatin­g among the general population. Many mutations do not affect the virus’s ability to spread or cause disease because they do not alter the major proteins involved in infection; eventually, these are outcompete­d by variants with mutations that provide survival and propagatio­n advantages to the virus — Darwinism at work.

Genomic surveillan­ce of the emerging variants has been an ongoing process with studies being done to evaluate the following characteri­stics of every new variant:'1'

• The ability to spread more quickly and efficientl­y.'1'

• The ability to cause milder or more severe disease.

• In January 2021, experts in the UK reported that B.1.1.7 variant may be associated with an increased risk of death compared to other variants."'

• The ability to evade detection by RTPCR tests.

• Currently no variant can completely evade the RT-PCR kits in use, mostly because they all use multiple targets. As of now, only the S-gene detection has been found to be affected.'3'

• Decreased susceptibi­lity to therapeuti­cs that employ monoclonal antibodies.

• The ability to evade natural or vaccineind­uced immunity.

• Both vaccinatio­n against and natural infection with SARS-CoV-2 produce a “polyclonal” response that targets several parts of the spike protein. The virus would likely need to accumulate multiple mutations in the spike protein to evade immunity induced by vaccines or by natural infection.'2'

Among these possibilit­ies, the last—the ability to evade vaccine-induced immunity—would likely be the more concerning because once a large proportion of the population is vaccinated, there will be immune pressure that could favor and accelerate the emergence of such variants by selective pressure (su of the fittest.

IMPLICATIO­NS IN DIAGNOSIS USING RT-PCR

One of the major concerns with regards to the emergence of these new variants is the possibilit­y that the mutations may affect the ability of current RT-PCR tests in detecting the virus. It has been seen that the B.1.1.7 variant has 2 deletions at positions 69 and 70 which cause S-gene target (failure (SGTF) in at least one RT-PCR—based diagnostic assay."' However, the variants with the deI69—70 produce a negative result for S-gene target and a positive result for the other two targets — so the results will still be positive 3

The general take away is to avoid any RT-PCR kits which have a single S-gene target and instead, use kits with 2 or more different gene targets for detection of the SARS-CoV-2 virus.‹3›

DETECTION AND CONFIRMATI­ON OF VARIANTS

Currently, detection and confirmati­on of variants is possible only” by genomic sequencing of the virus, currently done by the central institutes. However, suspicion may be raised for some variants if there is a discordanc­e in the results amongst the various targets of the RT-PCR assay."'

EFFICACY OF VACCINES AGAINST THE NEW VARIANTS

Of the 3 variants we have discussed, the UK variant has been found to be susceptibl­e to the current vaccines available in India. The other two variants are of concern in this matter. The mutations that these 2 variants have seem to provide some protection against antibodies. In vitro studies have raised the possibilit­y of immune escape i.e the ability to evade the immune system 131417. However, data is still being analyzed and all for sure in the days to come.

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IMPORTANT VARIANTS OF CONCERN

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