The role of genome sequence in combating Covid-19: Bangladesh perspective

Genome sequencing of the novel Coronavirus in Bangladesh has made headlines in recent times. So far, a total of 104 locally circulating virus isolates have been completely sequenced by different institutes and organizations in Bangladesh and have been submitted in the global repository (GISAID). Those released sequences have sparked excitement among local researchers and drawn public attention.

Having collected from infected individuals, Child Health Research Foundation (CHRF) first sequenced the virus from Bangladesh followed by DNA Solutions, Chittagong Veterinary and Animal Sciences University (CVASU)- Basic and Applied Research on Jute (BARJ)- Bangladesh Institute of Tropical and Infectious Disease (BITID), National Institute of Laboratory Medicine and Referral Center (NILMRC)- BCSIR, National Institute of Biotechnology (NIB), Dhaka University and Jashore University of Science and Technology (JUST).

This is a good start for Bangladesh, although we started late.

Viruses are not considered a living entity. Yet, there is blueprint of it - genetic material that we can sequence and read through to see the similarities or dissimilarities to compare with its cousins.

The approach of genome sequencing is so powerful that it can even predict what the virus may do in near future provided that we have accumulated enough data on it. Covid-19 has created a renewed interest in viral genomes.

What is genome sequence?

Genome is the code of life which consists of genes. Individual genes perform specific functions. Genome sequence reveals the structure and function of a genome. In all living organisms, genes are made up of DNA. But in the viruses, both DNA and RNA can play the role.

DNA or RNA are the two different types of ribonucleic acids that encodes genetic information of life. In fact, viruses are acellular (not a living cell) and they can only live in their host cells (for novel coronavirus the host is human) for their propagation to other hosts.

From the genome sequence of novel Coronavirus we can extract biological information about the nature of its genes and their functions and we can also understand how the genome is changing continuously.  

Why is genome sequence important?

Genome sequences or whole genomes sequence (WGS) is important because it provides the complete manual of the virus - how it operates, infects others and transmits in population rapidly. And therefore, knowing the operating manual of the contagion can potentially help management of the disease.

SARS-CoV-2, the virus behind Covid-19 pandemic is an RNA virus. RNA viruses generally show higher rate of mutation (change in its genome) compared to DNA viruses and this natural capability makes this virus  unstoppable until a vaccine or drug is found.

Due to its nature, this virus continuously brings changes in its manual (genome sequence). By analysing the changes, we can find out the different versions (what we call strains) of the virus that are evolving.  By using genome sequences of emerging strains (mutant form of virus) it is possible to map the spread of the virus in real time.

Better understanding of the genetic makeup of the virus and the dynamics of its genome sequence changes could ultimately save lives by informing strategies for public health and clinical care, as well as facilitating the design of therapies and vaccines to combat the virus.

Sequencing genome of an emerging pathogen is a routine practice now, both in research and clinical settings, in case of any infectious disease outbreak. Therefore, we have seen sequencing this viral genome has started since the pandemic broke out in China and the efforts continued till to date in order to keep track of genetic changes that is occurring in the virus as it spreads around the globe.

The global landscape of SARS-CoV-2 is dazzling at present with a compilation of 50,000 genome sequences submitted in a global repository called GISAID. Needless to say, this number will grow staggeringly high as long as the pandemic continues.

This is the highest number of sequences generated in such a short period of time for a single pathogen.

How will genome information help us?

Firstly, finding and understanding the changes (mutations) in sequence of the viral genomes collected from different patients allows researchers to build a viral 'family tree' by using "bioinformatics" tools. In order to monitor disease spread within and between populations over time, these bioinformatics analyses are critical. Moreover, those insights facilitate scientists to identify infection "hotspots".

We can also apply these information to spot individuals who are acting as "super spreaders"- persons who are transmitting the virus to unusually larger number of people. Moreover, in the initial stages of the epidemic, sequencing can be used to find out how many new cases of disease are imported or came from local transmission.

Secondly, understanding the viral genome sequence assists researchers in designing effective drugs, therapies and vaccines that target specific sequences of genomes or genes of the virus. A third important area is clinical management of patients, where it is critical to keep an eye on emerging variants and any potential association with particular patterns of symptoms or severity of disease.

Other significant contributions that genome sequence may provide includes developing predictive mathematical models based on past or current outbreaks. Different estimates and measurements can help us to project long term trends of a virus and possible outcomes of interventions.

Moreover, genome sequences may also help determine the factors driving the transmission as well as the transmission chain. Additionally, in case of a zoonotic virus such as SARS-CoV-2, local zoonosis or inter species transmission (pathogenic shift) of an emerging pathogen can be identified and kept under surveillance by using genome sequences.

Unanswered questions

In the current pandemic of Covid-19, hundreds of questions of multidisciplinary importance are out there which are not clearly known yet. For example, where did the virus actually originate? How did it jump to human? Why do children and adolescents seem to be less vulnerable than adults? What is the dynamics of SARS-CoV-2 mutation? How quick this virus is evolving? Is the virus emerging as a more virulent pathogen? Is it becoming weak in terms of pathogenicity? Why are some countries suffering more from the virus when compared to other countries? Is it possible to develop population specific vaccine or drugs? Is it possible to design population specific interventions?

Genome sequences can gradually answer these questions in combination with other important factors.

From our perspective, the most significant information that can be extracted from the viral genome sequence at this moment is identification of prevalent viral strains circulating in the country. Similarly, identification of infection hotspots or super-spreaders is equally important so that strategies for effective public health intervention can be formulated.

At this moment we need to select Covid-19 hotspots and hundreds of isolates have to be sequenced in order to get an in-depth idea about the pandemic scenario in Bangladesh. This tracking will have to continue as long as the virus keeps spreading in our population. Otherwise, we will fail to translate the true potential of genome sequencing. In long run, a rich pile of genome sequence may help develop a vaccine targeting our own population, if we are really able translate it.

Based on available information and predictions, we can correlate the havoc it has done to another country with their geographical, epidemiological or even demographic features and then extrapolate an effect of Covid-19 infection on us. If we find a correlation of genetic or demographic factors with efficacy, an effective vaccine or drug against Covid-19 infection, we may want to test the feasibility of it on our population before going for a mass import or mass population.

Though late, it is good to see Bangladesh has joined the race of sequencing the genome of local SARS-CoV-2 isolates. Conclusions have been made based on first few sequences (even with single one) of Covid-19's plausible route to Bangladesh. They might seem exciting at this point, but to attain scientific rigor and avoid a bias we must focus on sequencing isolates from afflicted parts of the country covering a good representative population.

We have got to look at scores, not few! Otherwise, it can skew the true scenario of the circulating SARS-CoV-2 isolates in Bangladeshi population. Most importantly, we should not let our rational thought process drift into hasty conclusions with an uncontrollable urge to device a quick remedy against this pandemic plague. We can neither overestimate, nor underestimate the power of genome sequencing. Therefore, pragmatic application is the prerequisite to deliver its potentials.

Dr Muhammad Sougatul Islam is Director, BioTED, Bangladesh and Dr AM Mahedi Hasan is Research Fellow, UCL Cancer Institute, UCL, UK.