The genetic code of an organism is a collection of all the characteristics it possesses. If we were to draw parallels, the genetic code is similar to a book. It is comprised of letters, which go on to form sentences, paragraphs, sections, chapters. The ‘letters’ which form the basic units of our DNA are called “nucleotides”. Combinations of nucleotides constitute a ‘paragraph’, or a “gene”, and various genes link together to make up the “genome”, or the ‘book’. In order to read a book, we need a set of eyes. In order to read a set of genes, we require a genomic sequencer.
As they say, “Aik nuqte ne hamain mahram se mujrim kar dia.” By changing a single letter in a word, it is possible to change its entire meaning. If viruses are allowed to infect individuals uninterruptedly, they tend to evolve rapidly, through changes in their viral gene code. This evolutionary process gives rise to “mutations”. As a result of which, new variants of a virus emerge constantly, as seen frequently in viruses which are causes of common infectious diseases, such as the flu virus. The Centre for Disease Control (CDC), USA, has labelled SARS-CoV-2 variants into three basic categories: (i) variant of interest, (ii) variant of concern, and (iii) variant of high consequences. This classification is based on multiple criteria, such as transmissibility, ability to cause severe disease, and ability to bypass vaccine immunity. Fortunately, no variant has yet been classified as a ‘variant of high consequence’. However, there are noticeable examples in the other two categories, such as B1.1.7, B1.351, and B.1.617.2 (Delta variant), that have put the global pandemic response in a complete state of disarray. Countries across the world where SARS-CoV-2 variants of concern have become dominant, including Brazil, Peru, Indonesia, the UK, USA, Germany, France, Spain South Africa, are witnessing huge resurgence in cases, and hospitalisations.
In order to track the continuous evolution of the SARS-CoV-2 virus, and to assess how much it has imperilled disease fighting response, countries across the globe have initiated ‘variant detection’, commonly known as genomic surveillance, programs. Briefly, there are two types of scenarios where variant detection becomes necessary. First, where we observe an unusual or rapid increase in cases, or an unusually high proportion of severe illness. Second, where random testing is being performed to keep track of the evolving virus. Pakistan, unfortunately, has yet to establish a concerted genomic surveillance program. To date, the country has only managed to publish 500 genomic sequences, compared to half a million sequences published by the US. It is about time Pakistan increased its genomic surveillance capacity.
Ever since the outbreak of the Covid-19 pandemic in Khyber Pakhtunkhwa (KP), the Public Health Reference Laboratory (PHRL) at Khyber Medical University (KMU), has been at the forefront of disease response. It was the first laboratory in KP to initiate real-time reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2, and has played a central role in disease surveillance. At present, PHRL is the fifth largest Covid-19 laboratory in Pakistan, having conducted more than 800,000 tests in a span of 16 months.
At PHRL, a “multi-staged” approach is used, under which the laboratory will continue using RT-PCR for detection of SARS-CoV-2 virus. Out of the positive samples, an estimated 3-5% will be tested with “variant detection PCR”, a technique that can tell the common known variants.
Should there be any cases which cannot be reliably tested on ‘variant detection PCR’, the next option available to us would be “Sanger Sequencing”, which is another rapid and cheap technique for DNA sequencing.
This method can aid in identifying genetic changes within short regions of interest in viral genome, similar to how autocorrect would be used to pick up errors in the most important chapters of a book. PHRL has acquired a Sanger Sequencer, and enough reagents to run 3000 tests for the next one year. In addition to Sanger Sequencing - where we look at small parts of the virus genome - PHRL has acquired the capability to read the entire genome, using “Next Generation Sequencing” (NGS).
With collaboration from John Hopkins University and US CDC, PHRL has received the most advanced NGS equipment, ‘Mini-Ion’. Since this technique is expensive to run, it is important we reserve it for assessing samples with the highest likelihood of mutations. In the next one year, we hope to perform 300 whole genome sequencing analyses.
As we move forward in the pandemic, our most powerful weapons to prevent SARS-CoV-2 variants of concern, such as Delta, becoming widespread, are vaccines. We believe that with concerted efforts towards uptake in vaccination numbers, coupled with rapid outbreak response, and social responsibility, Pakistan can pass through these testing times with minimal damage to public health, economy, and the social fabric of our society.
(The writer has received Tamgha-e-Imtiaz in the field of medicine in the country. He is an associate professor, Director of Public Health Lab, KP)
Copyright Business Recorder, 2021
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