CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh, India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

Today, World is craving for more of it. The Omicron pandemic has unearthed the importance of genomic sequencing and made it a popular and commonly requested test.

What is Genome Sequencing?

  • Genomic sequencing is the process of recording a virus’ genetic code, to be more precise it is the way of finding out gene sequences in the RNA (or DNA) of any organism and comparing the sequence to previous records.

How does Gene sequencing help?

  • It allows researchers to understand if the virus is new to the human population.
  • Gene sequence is the basic requirement to develop a vaccine. Most commonly used vaccines during the pandemic like mRNA vaccines from Pfizer and Vector based Vaccine from Serum Institute of India could be developed in record time because of availability of Viral Genome which was decoded as early as 11th January 2020, even before pandemic had spread to many parts of World.
  • Sequencing has allowed COVID-19 to be the first virus whose spread is being monitored in real-time and on a global scale.
  • During the course of Pandemic, repeated viral gene sequencing helped detect new variants and analyse their origin and behaviour.

How old is Genome Sequencing?

  • Research had been going on for long but reliable results started 10 years back.
  • If the pandemic had happened ten years ago, what would it have looked like?
  • Doubtless virus could have caused much more damage. World might have depended upon fewer vaccines and lesser doses.

How Genome sequencing changed the Shape of Pandemic apart from quick Vaccines?

  • Sequencing may not be new – what’s different today is the amount of sequencing being done and the increasing demand for more tests.
  • Genomes of variants are being tested around the world at an unprecedented rate, making COVID-19 one of the most highly tested outbreaks ever.
  • With this information we can then track how different forms of the virus are spreading locally, nationally and internationally.
  • It makes COVID-19 the first outbreak to be tracked in near real-time on a global scale.
  • Changed sequence in particular regions of Virus Genome help scientist find out if a particular subset of mutations will affect spike protein of virus and hence its behaviour in terms of transmission and virulence. For Sars-Cov-2 mutations in genes coding for Spike Proteins and Furin Cleavage site have been of particular concern.
  • This helps in controlling the virus. For example, together with PCR testing, sequencing helped reveal the emergence of the alpha variant in winter 2020 and delta variant in early 2021 and lately Omicron.

How Omicron has fuelled the demand of Genome Testing?

  • Identification of Omicron Variant has really turbocharged the demand for Genome testing.
  • Current wave of pandemic in being driven by two variants – Delta and Omicron. Both have different prognosis and different treatments.
  • High-risk patients carrying the Delta variant could benefit greatly from two particular monoclonal antibody treatments from Eli Lilly and Regeneron. Treatments have shown to reduce both hospitalization and death.
  • But those medications would most likely do nothing for patients with Omicron, who would only respond to a third antibody treatment – Sotrovimab developed by GSK.
  • Most doctors have no way to determine which variant of the coronavirus a patient is carrying, a distinction that could mean the difference between life and death.
  • Patients too want to remain informed of the virus they are harbouring. It would obviously help them take an informed decision knowing if it were Omicron or Delta.
  • Omicron being a benign variant would instil a sense of relaxation and hope for quick recovery.

One would be surprised to know that current Genome Testing Equipment is of the size of hand-held stapler and its cost could be as low as Rs 75000 – or just $1000.

Genome Sequencing is strictly in Govt Control. Why?

How many labs in India are doing Genome testing?

How other countries in World are doing Omicron analysis?

Genome testing framework in India?

  • For genome testing, RTPCR positive samples are sent to the designated lab of INSACOG – the apex body for Genome sequencing in India.
  • The Indian SARS-CoV-2 Genomic Consortia (INSACOG) was launched on 20th December 2020 with the aim to monitor the genomic variations in the SARS-CoV-2. INSACOG is a consortium of 10 central labs and 28 satellite labs in various parts of Country.

How many samples have been processed by INSACOG?

  • INSACOG was set up with the aim to sequence at least 5% of COVID-19 samples. But only 1% has been achieved yet. Although more than 100,000 samples have been processed till date.

Does INSACOG convey results of Omicron testing to patients?

  • No, INSACOG works within the Central government’s control. Results of samples are not communicated to individuals rather used for research and policy making decisions.

Case Load of Omicron testing in India?

  • Till now, Omicron has been detected in more than 29 states of India.
  • As of 17th January 2022, 8,209 Omicron cases have been reported across India. While India reported 2.58 lakh new cases of Covid-19 on 17 January 2021. Major circulating variant in India presently being Omicron, Omicron case numbers represent just the tip of iceberg because not more than 1% samples are being processed for Genome testing.

Previously Delhi was doing Genome analysis of all positive case, why did Govt change policy?

  • Till December-end, Delhi sequenced all its positive samples when the number of Covid cases was low. The Delhi Govt reported that 81 percent of the samples sequenced on the New Year’s weekend were of the Omicron variant. Once it was clear that the new variant was driving the surge in cases, the government stopped sequencing all samples.

World Scenario of Omicron!

  • Omicron has spread to more than 140 nations starting from Botswana since mid Nov 2021.
  • As of January 17, 2022, the United Kingdom had reported the highest number of SARS-CoV-2 Omicron cases, with over 161 thousand cases. Next in Omicron reporting is USA.

Genome testing in other countries including USA and UK?

  • World over, Genome testing is controlled by respective Governments. Presently no govt is able to meet the rising demand of the testing. All Governments share their data with GISAID, which is global science initiative and primary source established in 2008 with Headquarters in Munich. Now GISAID database has become the world’s largest repository for SARS-CoV-2 sequences.

Do we have Better Genome Sequencers to process thousands of samples?

  • Yes, Genomic sequencing has now evolved to a stage where large sequencers can process even thousands of samples simultaneously. However, Genome sequencing is a technically demanding job where experts must purify the samples appropriately and get them ready to be used in sequencers. Currently, turnaround time for a Genome sequencing report is 5 to 7 days.

Nanopore Technology – road to mass sequencing. How does it work?

  • Various technologies can be used for gene sequencing, but a particularly important one in taking us to where we are is nanopore sequencing. Ten years ago, this technology wasn’t available as it is today. Here’s how it works.
  • The Sars Cov-2 virus’s genome consists of RNA, and each of its 30,000 characters is one of the four building blocks, represented by the letters A, G, C and U. Sequencing is the process of identifying their unique order.
  • First the RNA is converted to DNA. Then, like a long thread of cotton being pulled through a pinhole in a sheet of fabric, the DNA is pulled through a pore in a membrane. This nanopore is a million times smaller than a pin head. As each building block of DNA passes through the nanopore, it gives off a unique signal. A sensor detects the signal changes, and a computer program decrypts this to reveal the sequence.

Nano Sequencing – The New Affordable hallmark!

  • Amazingly, the flagship machine for doing nanopore sequencing – the MinION, released by Oxford Nanopore Technologies (ONT) in 2014 – is only the size of a stapler; other sequencing techniques (such as those developed by Illumina and Pacific BioSciences) generally require bulky equipment and a well-stocked lab.

Experience with Nano Tech

  • Using the technology, scientist could set up Pop-up labs even in areas lacking scientific infrastructure, during the 2013-16 Ebola outbreak and then during the Zika epidemic of 2015-16. These make shift labs helped scientists to identify where each outbreak originated.
  • Nanopore sequencing of Zika and Ebola laid the foundation for sequencing the coronavirus today. Govts just need to utilize it on never-before-seen scale.

Once Pandemic ends, will genome labs become idle?

  • Genome sequencing also has a role to play in the future of healthcare and medicine. It has the potential to diagnose rare genetic disorders, gene therapy informs personalised medicine, and monitor the ever-increasing threat of drug resistance. Labs set up today will unlock unseen frontiers in future and benefit the mankind. With so much demand for Genome testing let this opportunity not be lost.

What are risks involved with Genome analysis?

  • There are a lot of fears and concerns. Routine genome sequencing could overwhelm doctors and patients with confusing and sometimes alarming information, leading to anxiety and stress, as well as expensive and sometimes dangerous follow-up testing. Privacy concerns and family suits might increase.

But Governments can always exercise control by legislations and strict punishments.

  • Various other potentially dangerous but beneficial programmes like organ transportation, IVF, child surrogacy, prenatal diagnostics ultrasounds and genetics have shown the way that responsible citizen behaviour and strict legislative control can yield good results while protecting society from misuse of scientific advancements.

Way ahead to Increase foot print of Genome analysis in India?

  • Public private partnership is the only plausible answer. Govt should permit Genome testing in Private Labs with result sharing on commercial basis. Genome testing set up are already available in many corporate hospitals. Many of them are allowed to do Genetic analysis for research purposes but not permitted to issue reports on commercial basis. When allowed, many more labs would be ready to set up Genome testing facility using equipment which is available from $1000 to >$50000.
  • During pandemic tests like IL-6 descended from research labs to next door street laboratory. RTPCR became a common name. Similarly, expanding Gene Testing Network for nation, could be a Golden Opportunity, let it not become an opportunity lost.

CME INDIA Tail Piece

  • Four international travellers had tested positive for COVID-19 on Nov. 11, 2021, four days after entering the country.
  • Interestingly, In the early days of November, laboratory technicians at Lancet Laboratories in Pretoria, South Africa, found unusual features in samples they were testing for the coronavirus.
  • Essentially, a gene was missing in what would be a normal genome profile of the virus Thus, PCR tests weren’t detecting one of their expected targets, a signal that something about the virus had changed.
  • The cases were genetically sequenced, wherein the genetic code of the virus was analysed to look for worrying changes.
  • When they compared it with other sequences circulating in Botswana, they realized this is an unusual pattern of mutations.
  • The number of mutations that it had was just unbelievable.
  • The scientists discovered a variant they had never encountered before.
  • And soon, they alerted the world to what would become known as the omicron variant.
  • On the 24th, Nov, 2021 South Africa went ahead and reported to the WHO. On the 26th, the WHO convened a meeting and it was called a variant of concern.
  • Botswana and South Africa alerted the world to this variant, but it was found among travellers who reportedly flew in from Europe.
  • Just where and when Omicron first emerged is still unknown.
  • Later it was found that the variant was reported in the Netherlands a week before the announcement from Africa.



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