Omicron, the new SARS-CoV-2 variant, has led to increased fear and many questions. Everyone wants to understand how infectious the variant is and the science behind how variants rise and how they are identified.
Omicron is the fifth variant of concern and joins the Alpha, Beta, Gamma, and Delta variant in the list of variants of concern. Variants that have increased transmissibility and virulence, and decreased the effectiveness of public health measures such as medicines and vaccines are classified as variants of concern.
Although we have been hearing of different variants, earlier with their strain names before they were characterised by Greek alphabets by the World Health Organisation, it is not really clear how they actually occur and how they are identified. It is only when the Ministry of Health and Family Welfare shared about reading the DNA of the virus that people started learning about the actual scientific processes.
BOOM spoke to Dr. Krishanpal Karmodiya, Assistant Professor, Indian Institutes of Scientific Education and Research, Pune who works on whole-genome sequencing. We asked him how variants evolve and how scientific processes like genomic sequencing help in understanding how they mutate.
How Do Variants In A Virus Occur?
According to the US Centres of Disease Control and Prevention, as the virus spreads, it has new opportunities to change and may become more difficult to stop.
Explaining how mutation occurs, Karmodiya shared, "The virus can grow only inside the host cell. While growing, multiple copies of the virus are produced per cell. In this multiplication process, the virus makes errors (or mutations) during the duplication of the genome. These mutations are randomly generated and many of them have no effect to the virus or to the host (in this case human)."
However, he added, there are some mutations that can increase the transmissibility (speed) or severity (deadliness) of the virus when they are transmitted to another host.
The biologist whose main area of research is studying the genetic build of the protozoan Plasmodium that causes malaria said that the "mutations with increased severity have generally less transmissibility". This is because, he said, the host is eliminated faster thus limiting the spread.
"Nature maintains a balance between severity and transmission," he added.
These mutations occur in different regions of the virus and can have different effects on how the virus affects the host.
How Are Variants Detected?
Variants are detected by a process of genome sequencing. A mere RT-PCR test is not enough to gauge whether one is affected by a particular variant. If the RT-PCR test does not identify the S gene on the spike protein, the person is assumed to be affected by the Omicron variant. However, the final decision can only be deduced after the sample is sent for genomic sequencing.
What Is Genome Sequencing?
Ever since variants were first discussed, the concept of genome sequencing has also been in the spotlight. The Ministry of Health and Family Welfare formed a consortium of 37 labs that could undertake this sequencing activity to recognise any changes in the original virus.
Karmodiya broke down the process of genome sequencing. "The genetic material of the organism (RNA, in the case of SARS-CoV-2) is isolated in a designated facility for sequencing. This isolated RNA is then converted into DNA and analyzed using Next Generation of DNA sequencing machines."
The assistant professor further added that the entire genome of the virus is created for each sample using computer tools.
"The genome sequence is then compared with the existing virus sequences (or variants of concern) to identify the variant type. Genome sequencing also provides information on novel mutations (variants) which are analyzed for association with local outbreaks, reinfections, or vaccine breakthroughs," Karmodiya said.
How Are Existing Sequences Used?
The existing sequences that Karmodiya mentions are present from the time the virus was first isolated and compared to genomes that scientists have been mapping over years.
Karmodiya highlighted that every sequence that is generated is submitted to various databases.
"Organizations such as INSACOG (Indian SARS-CoV-2 Genomics Consortium) manage databases. All these sequences are available to integrate and analyze to the scientific community. The existing sequences are then used to check whether the sample of interest has new or existing mutations (and thus strain)," Karmodiya shared.
The original SARS-CoV-2 was identified from China and post isolation, many people sequenced the primary samples and uploaded the sequence for others to use and compare on databases such as GISAID and NCBI. These two databases are the most frequently used platforms for sharing data about sequences that can be later used by other scientists to find changes.
By comparing the genome of the Omicron variant to the original strain and the existing six variants- alpha, beta, gamma, delta, kappa, and mu, the scientists in South Africa discovered that the new variant has over 45 changes, and close to 30 mutations on the spike protein. The spike protein helps the virus bind faster to the host cell.
How Long Does Sequencing Take?
Dr. Sujeet Singh, Director of the National Centres of Disease Control in a press conference held on December 2 said that the 37 laboratories had sequenced over 6500 samples in the month of November. Between November 24, the day South Africa announced that they had identified Omicron and December 2, the labs had sequenced 883 samples from at-risk countries.
On average, the approximate time it takes for sequencing, Karmodiya said is 24-48 hours.
"There are three major steps in genome sequencing: sample preparation, sequencing and data analysis. It is dependent on the genome size of the organisms as well as on the platform (sequencing instrument) used for the sequencing. Moreover, sequencing instruments have the capability to sequence a large number of samples per run to make it cost-effective and affordable," Karmodiya explained.
The biologist said that if the sample number for sequencing is lesser than the instrument can hold, it could be a limiting factor and lead to lesser insights about the nature of the variant.
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