The year 2020 will be remembered for the appearance of a new virus: the SARS coronavirus 2 (SARS-CoV-2) and the Covid-19 pandemic that it caused. With a few more days to go, 2020 is projected to close with approximately 84 million confirmed Covid-19 cases and more than 1.8 million deaths.
Despite this sadness, this has also been a year of hope, with vaccine development, testing and approval at remarkable speed. For the first time in history, a human disease pandemic would be controlled by vaccines in real time.
Nobel laureate Joshua Lederberg, one of the most influential thinkers in modern biology, once said, “The greatest threat to man’s continued dominance on the planet is the virus.” Two recent developments remind us why viruses can be such formidable adversaries.
With the discovery of 58 people who tested positive for the new coronavirus in Antarctica, the pandemic has reached every continent. And a mutant virus It has emerged in the UK, which threatens to shut down the world once again, a world that is just beginning to recover from blockades and restrictions on movement.
Virus mutation
The genetic material or genome of SARS-CoV-2 is a ribonucleic acid (RNA) composed of more than 30,000 units (called nucleotides). Among the families of RNA viruses, coronaviruses have the largest genome. Most other RNA viruses have an average of about 10,000 nucleotides. When genomes replicate, any genome, be it DNA or RNA, from the smallest viruses to humans, there are random errors (or mutations). While higher organisms have the machinery to correct these errors, viruses, and especially RNA viruses, do not.
Most mutations are harmful, and these viruses are never seen. Only mutations that offer any selective advantage result in the evolution of new viral variants.
Evolution also requires selection pressure. For a virus, this could be its ability to better infect and multiply in greater numbers or evade the host’s immunity. The low probability of these events is offset by the high multiplication rates of the virus. For example, each cell infected with coronavirus produces around 1,000 new virus particles in less than 12 hours.
The mutant in the UK
A distinct phylogenetic group or lineage (named B.1.1.7) of SARS-CoV-2 was recently discovered in the UK. The first two viruses of this lineage were collected on September 20 and 21 in Kent and Greater London, respectively. As of December 15, this lineage contained 1,623 viruses: 555 from Kent, 519 from Greater London, 545 from other regions of the UK, including Scotland and Wales, and four from Australia, Denmark, Italy and the Netherlands.
In another ten days, on December 25, the number of these virus variants has more than doubled to 3,575; mainly from the UK, but now also from France, Ireland, Israel, Hong Kong and Singapore. 📣 Express explained is now in Telegram. Click here to join our channel (@ieexplained) and keep up to date with the latest
What the mutation does
Compared to the parent strains of SARS-CoV-2, viruses of this lineage have accumulated 23 mutations in 5 genes. Of these, there are 17 non-synonymous and six synonymous mutations; the former also changes an amino acid at that site in the protein. Importantly, of the 17 non-synonymous mutations, eight are in the spike protein, the protein that allows the virus to attach itself to and enter cells.
The expert
DR. SHAHID JAMEEL is one of the best known virologists in India. He is currently Director of the Trivedi School of Biosciences at Ashoka University, previously worked for the Delhi-based International Center for Genetic Engineering and Biotechnology, and later served as Executive Director of the Wellcome Trust / DBT Alliance, which funds research at Health.
The N501Y mutation in one of the key contact residues in the receptor-binding domain (RBD) of the spike protein increases its affinity for the ACE2 receptor. The P681H mutation at the cleavage site between the S1 and S2 domains of the spike protein promotes entry into susceptible cells and increases transmission in animal models of infection.
The change in N501Y is also associated with increased infectivity and virulence in animal models. Both mutations were previously seen independently, but have been linked in UK variant viruses. The result is a virus that spreads faster than before.
The reason for concern …
There is widespread concern that these mutations may prevent current tests from detecting the virus, make it more lethal, or allow it to evade vaccines in development. So far there is no evidence of any of these. After all, these variants were found in people who were identified as positive by currently available RT-PCR tests.
However, although there is no evidence of a more serious disease, there is clear evidence that this variant is more contagious. Those infected produce more virus in the nose and throat, and that leads to more virus shedding and more person-to-person transmission.
While these variants do not appear to be more lethal, with more infected people there would be a greater number (not percentages) of serious infections and deaths. This should be cause for concern.
… And reason not
Although there are multiple mutations in the spike protein, most experts believe that vaccines currently in development would also work with variant viruses. Vineet Menachery, assistant professor of microbiology and immunology in the medical branch at the University of Texas in Galveston, USA, has provided the first evidence for this.
His laboratory compared the effectiveness of serum samples from recovered Covid-19 patients in neutralizing viruses with or without the N501Y mutation. They found no difference. Although it was only shared on Twitter on December 23 and not yet part of a post, these results are encouraging and reassuring.
Fly, not mutation
India has stopped all flights from the UK and increased surveillance at airports to stop the import of highly communicable variants. Although apparently a reasonable strategy, such variants could easily develop within the country as well. After all, India has more than 10 million confirmed infections and it is estimated that 150-200 million people are already infected.
A fast-spreading variant called 501.V2 arose independently in South Africa and shares the N501Y mutation with the UK variants. Although the peak variant N501Y has not yet been found in India, viruses with the P681H mutation began to emerge in July and currently 14% of SARS-CoV-2 circulating in India carry this mutation.
These viruses are mainly from Maharashtra, and some are also from West Bengal. It would only take one more mutation to get to where the UK is today. And that should also concern us in India.
Quick reaction is key
To detect the emergence of new viral variants before they spread widely in the population, the World Health Organization (WHO) recommends determining the genomic sequence of the virus in at least one in 300 confirmed cases (or 0.33%) . The UK has sequenced 135,572 or 6.2% of viral variants of its 2.19 million cases, while South Africa and the US have reported genomic sequences of 0.3% of confirmed cases.
However, India has so far sequenced only 4,976 or 0.05% of viruses from its more than 10 million cases. At this rate, we will remain oblivious to the emergence of new variants until it is too late. A basic element of disease surveillance is adequate coverage and density to detect events before they spread widely.
Favorable conditions for India
Another cause for concern is that the conditions that are supposed to give rise to the UK variant are also present in India. Immunocompromised or immunosuppressed patients, who are chronically infected with SARS-CoV-2, remain positive for viral RNA for 2-4 months instead of the usual 2-3 weeks. These patients are often treated with convalescent plasma (sometimes more than once) and usually with the drug remdesivir as well.
Sequencing of the virus genome from these patients has revealed an unusually large number of nucleotide changes. Intrapatient virus genetic diversity is also known to increase after plasma therapy. Poor nutritional status is a known cause of a weak immune system, and doctors in India have reported chronic infection in a subset of patients.
Several unknowns remain
Plasma therapy and remdesivir have also been widely used to treat Covid-19 patients in India. Additionally, plasma has been administered in India without prior testing for neutralizing antibody levels. All of this creates opportunities for variants of the UK type to emerge in India as well. But we haven’t sequenced enough to know if that has happened.
Even with low coverage, sequences from India are skewed for urban locations, especially metropolitan areas where sequencing labs are located. This needs a broader coverage to include all parts of the country. The Indian Council of Medical Research can facilitate this process by providing access to samples from Covid-19 patients to research laboratories that have the capacity for genomic sequencing and data analysis. Real-time surveillance will provide dense and granular data to establish evidence-based policies.
Moving forward with ‘SMS’
As vaccines are more widely deployed, there will be more selection pressures on the virus to change. Vaccine escape mutants are well known for other viruses and will also emerge for SARS-CoV2. Only proper genetic monitoring will detect any vaccine failure in time.
As we move into 2021, the message for policy makers and the public is clear. Public health supervisors must continually seek new evidence to formulate policies at the population level. On an individual level, each of us must work to reduce the transmission of the virus: less transmission means fewer opportunities for the virus to change. And SMS is the only tool available to us right now: social distancing, masks, and disinfection.
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