by Dr Prachi Singh
Image Courtesy: Pixabay
COVID-19 has made several not-so-known genetic fields famous, genomics -bedrock of all- is one of them!
What is Genomics?
Genomics is the study of structural, functional, and evolutionary aspects of the genomes: the blueprint of life coded in the form of DNA/RNA. Genome sequencing is revealing the order of DNA nucleotides or bases in the genome of the organism. The practice of utilizing the whole genome sequencing features of epidemiologic significance can be described as genomic epidemiology, which is one of the divisions of modern genetic technology.
The crisis caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is not the first-time humankind is witnessing a pandemic. However, never in human history, we were privileged enough to rapidly identify and potentially neutralize the invisible threat among us. Unlike the 2002 SARS outbreak when it took almost six months to identify the virus, the genetic architecture of SARS-CoV-2 was resolved and shared by China within a few weeks of its first reported case.
Soon after the genome of SARS-CoV-2 was shared, the virus-specific primers and antibodies were designed to perform the diagnosis using Real-time Polymerase Chain Reaction (RT-PCR) and serological assays. The genome sequencing of SARS-CoV-2 is also helping uncover the epidemiology of this coronavirus. Thus, here, genomic epidemiology is finding its application in surveillance - unraveling the mystery of the origin of the virus, frequency and types of mutations in the viral strain, its spread patterns at different geographic locations. Further, genome sequencing is facilitating testing various therapeutic models, and most importantly informing the process of its vaccine formation. On the other hand, host genomics (humans in this case) is helping understand why some groups are at higher risk than others. A clear understanding of both the viral and human genomes is much promising to shape up our survival in the post-corona world.
This is the first time when the technique of genome sequencing is being used at such a large scale. So far, more than 23,000 genomic sequences have been shared on Global Initiative on Sharing All Influenza Data (GISAID) - a global real-time data-sharing platform. Major sequence databases including the National Center for Biotechnology Information (NCBI), DNA Data Bank of Japan (DDBJ), European Molecular Biology Laboratory (EMBL) are deluged with the coronavirus sequencing data. Nextstrain, an open-source project, is using genetic data from the virus to help scientists track its spread and evolution.
Figure 1. Genomic epidemiology of novel coronavirus showing distinct phylogenetic clades of the 4690 genomes sampled between Dec 2019 and Apr 2020. Sequence data are essential to design diagnostics, to trace the origin and spread of this outbreak, and to identify potential medical interventions (source: https://nextstrain.org).
The above phylogenetic tree shows the evolutionary relationship of the SARS-CoV-2 viruses from the ongoing pandemic among the countries infected so far. It shows the initial emergence of the virus in Wuhan, China, which continued to transmit from human-to-human leading to spread across the globe. A study by Forster et al. 2020 shows that SARS-CoV-2 genomes are under “selection pressure” in the human hosts, therefore much susceptible to mutations inside its host. This justifies why we are witnessing increasing subtypes of this virus.
India has so far reported 28 unique viral sequences. On 13th March, the National Institute of Virology isolated 11 viral strains, making India the 5th country after China, Japan, Thailand, United States of America to decode the entire genome sequence. Council of Scientific and Industrial Research is currently sequencing more than 500 genomes from all over the country under a recently launched project called ‘SEQ-Mission’. Private sector players like Redcliffe Life Sciences, a diagnostics company based in Noida, claims to have required expertise and technology and has proposed a partnership for sequencing the genome to the Indian Council of Medical Research (ICMR) and the Ministry of Health. However, ICMR is being cautious and not allowing private labs to uptake the process of sequencing considering the strict standards required for the purpose. Presently India has 40 labs under ICMR network having biosafety level-3 (BSL-3) required to undertake the sequencing of viruses.
Treatment and Vaccine
The most important question on the planet right now is when the treatment and vaccine for COVID-19 will be available?
After decoding and annotating the SARS-CoV-2 genome, researchers are now able to conduct the experiments using sophisticated technologies like single-cell omics etc. which reveal the complex survival strategies between the virus and the host. Knowing these viral proteins and strategies help to identify potential therapeutic targets and allows us not only to look for antiviral or host-directed therapies but also for the vaccines. Currently, there are 210 treatments under consideration and 125 vaccines are in development and these numbers are increasing daily.
The WHO has organized a ‘solidarity trial’, wherein 1650 people (including two Indians) have volunteered so far, to compare the treatment options for COVID-19. The four drugs under trial are Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Hydroxychloroquine. It is expected that the Solidarity Trial will take 80% less time than the randomized clinical trials which normally take years to design and conduct.
Further, it is speculated by few that there might be a vaccine available by September 2020, however, many maintain the prediction that there might not be any vaccine before the mid-year 2021. In India, Serum Institute of India- Pune, has partnered with the Oxford Vaccine project which has started the human trial stage of the vaccine candidate called ChAdOx1 nCoV-19, from the last week of April, says that there might be a million doses of vaccine available by September 2020. Another potential vaccine-mRNA-1273 developed by an American biotech company Moderna and National Institute of Health in the USA is under phase-1 of trial and is about to enter the second phase soon. Moderna has already started manufacturing the potential vaccine on the premises of making it available to people as early as in July 2020 once it gets approved. These developments in the process of vaccine development are facilitated by identifying and sequencing the genome of SARS-COV-2!
Globally, coalitions are forging across to foster COVID-19 research. For example - the UK government has invested in the whole genome sequence alliance for COVID-19 and future pandemics. Canada backed its newly launched Canadian COVID Genomics Network (CanCOGeN) with substantial federal funding. The private sector is also contributing to genomic initiatives in several countries. Few examples are: In New York, a coalition called the COVID-19 Genomics Research Network has started with initial $2.5 million philanthropic funding; John Hopkins University has directed $6 million towards research on COVID; a private biopharmaceutical firm deCODE genetics along with Icelandic health authorities has conducted large-scale testing and sequencing, etc.
● Harnessing the preventive and curative potential of the public health genomics: In the wake of the current crisis, health policymakers can seize the potential of genomics for achieving public health goals. The gap between population health and genomics should be bridged with appropriate policies and regulations.
● Investing in biomedical research and development (R&D) infrastructure: Sudden burden on the global health infrastructure due to the current pandemic has once again emphasized that investing in public health and medical research is not avoidable. Modern genetic technologies of today are available due to the investments made in the past. In India, we spend thousands of crores on defense and space, but it is difficult to assess looking at the budget on how much India spends on genetic initiatives including genomics. In fact, in the union budget 2020, ₹2100 crore (≅$0.27 billion) are allocated to medical research. To put that in perspective, the USA spends around $182.3 billion out of which $ 39.5 billion comes from federal agencies. Now is the wake-up call to listen to the recommendation of public health experts to increase overall health spending which is just 1.6% of GDP this year and allocate more financial resources to biomedical research including genomics.
● Ensuring accessibility by designing appropriate financial arrangements: Once the treatment and vaccine for COVID-19 are available, measures should be taken to make vaccines accessible and affordable to everyone irrespective of their ability to afford it. It is important to have a suitable financial arrangement in place for overcoming the gap between the demand and supply of the therapies.
●Adopting an interdisciplinary approach and fostering international collaborations in biomedical R&D: Currently, India needs to mobilize all its scientific resources which include capacity available in the private sector. Private organizations should be enabled to deploy their resources in sequencing samples to add to the genomic pool of the virus and enable a better understanding of it. It is extremely important to see how the virus is evolving as the effectiveness of the vaccine depends on this information. If the SARS- CoV-2 significantly mutated in India, Indians need a different vaccine than others and even if not, it is wise to consider the possibility!
Further, it would be wise to make extensive international collaborative efforts to create robust and fair models of the delivery of treatment and care. As we know, without global collaboration and data sharing, we would not be hoping for the COVID-19 vaccine at this phenomenal speed. To reap such benefits in the future, collaborating with international partners would help.
● Robust institutional mechanisms: The current scientific culture still lacks transparency in biomedical R&D which is further exacerbated by the poor academic environment. Indian scientific research institutions have often been under the radar for the quality of work they produce and most recently for a weak administrative system for its apathy towards the emerging research requirements.
To sum up, there is an urgent need for both personal and political wisdom and actions to harness the full scientific potential of our time. Without it, it would be difficult to prevent avoidable deaths and enable maximum utilization of the resources to manage and avoid such pandemics. In the words of Dr. Yuval Noah Harari, “I think the biggest danger is not the virus itself. Humanity has all the scientific knowledge and technological tools to overcome the virus. The really big problem is our own inner demons, our own hatred, greed and ignorance.”
Dr Singh is an Independent Public health practitioner, and former consultant of World Health Organization (India Office) and National Health Systems Resource Centre, New Delhi. Views expressed in the article are personal to the author.
(The author would like to thank Mr. Madhur Sachan, PhD candidate at Center for Life in Extreme Environments, Portland State University, USA for his helpful advice).