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Genomic Surveillance and Diseases
Viruses, including SARS-CoV-2, are constantly mutating. As they move from person to person through transmission, their genetic code slightly changes. Most of these mutations are relatively insignificant. Once they move through vast swathes of people, they accumulate enough mutations to be called a “variant.” This is where genomic surveillance comes in; researchers can analyze the SARS-CoV-2 genomes of newly-infected people to track unique variations and monitor the change of the virus over time. For example, the SARS-CoV-2 B.1.1.7 variant, also called the “U.K. variant,” is estimated to be between 30-35 mutations away from the original strain detected in Wuhan, China at the beginning of the pandemic.
Genomic surveillance has proven to be an effective tool in outbreak investigation and virus evolution. During the Ebola virus epidemic in West Africa, genomic analyses established that the outbreak originated from a single zoonotic source. Viral genome sequencing also revealed the route that the Zika virus travelled from Brazil to Central America, Mexico, the Caribbean, and the United States.
Image is courtesy of The Financial Times.
How Does Genomic Surveillance Work?
Genomic surveillance requires genetic sequencing. In January 2020, Chinese and Australian researchers published the entire genome sequence of the virus. SARS-CoV-2 is a single-strand RNA virus whose RNA includes approximately 30,000 nucleotide bases. Scientists determine the order of the adenine, uracil, cytosine, and guanine bases. Each time the virus replicates itself, slight mutations occur which change the sequence of the nucleotides. The mutations build on every time an infection is passed. Through genetic sequencing, researchers can identify what mutations occurred in which patient. By comparing patient samples and epidemiological data, virus spread can be traced.
The coronavirus genome is enclosed within an envelope that contains proteins, such as Spike proteins (CDC).
Genes that code for distinct instructions to build the virus are represented by different colours. The UK, South Africa, and Brazil variants all share a mutation called N501Y which affects the spike protein genes, shown in brown (CDC).
N501Y replaces SARS-CoV-2’s 501st amino acid, possibly allowing it to bind more tightly to ACE2 receptors, making the virus more capable of establishing infection once it enters the body and accelerating the process of transmissions (CoVariants).
Genomic epidemiology has come of age during this pandemic.
- Oliver Pybus, Professor of Evolution and Infectious Diseases, University of Oxford
The key to effective genomic surveillance is widespread sequencing and sharing to monitor mutations and variants as they arise. In the past year, more than 360,000 SARS-CoV-2 genome sequences distributed over 140 countries have been uploaded to GISAID, an online database for viral genomes. Most countries have uploaded only small amounts of sequences.
Exceptions: The U.K. has uploaded 45% of the database’s total SARS-CoV-2 genomes, and Denmark has uploaded 7%.
501Y.V2 Sequences upload (Nature).
Coronaviruses mutate slower than influenza. At the beginning of the pandemic, critics warned that genomic surveillance efforts would be futile, only finding meaningless mutations; however, various initiatives have proven successful. In November 2020, a hospital in the South African province of Eastern Cape reported a highly suspicious number of COVID-19 cases to a sequencing team in the University of KwaZulu-Natal. The team combed through a sequence database and quickly a new variant in the area, which accounted for 90% of recent infections. This variant is now known as the 501Y.V2 or South African variant.
B.1.1.7 sequence upload (Nature).
In March 2020, the U.K. government invested £20 million (CAD $34.9 million) to launch the COVID-19 Genomics U.K. Consortium, which coordinates the collection of sequencing data from public health labs.
New York City (Bloomberg).
Some countries have been less successful in genomic epidemiology efforts, such as the United States, which has only uploaded less than 0.3% of its total COVID-19 infections. This compares with nearly 5% for Luxembourg, 12% for Denmark, and a remarkable 60% for Australia.
Image is courtesy of Nature.
The U.S. did launch a sequencing program in May 2020 called SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance). But, it is less well-coordinated than the U.K., as it is not a national system. Academic laboratories do most of the sequencing and volunteer to contribute to SPHERES, but they don’t need to. This means that variants will be uncovered much quicker in places with active labs, such as New York City and Boston, than in areas that don’t. This is an issue because the more a virus circulates, the more opportunities it has to mutate.
Therefore, it is clear that sequencing needs to become a more central part of pandemic preparation in order to tackle problematic variants of infectious diseases. As Stanford microbiologist David Relman says, “...anybody who has the means and interest to engage in genomics is certainly encouraged to do so.”
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Article Author: Sara Gehlaut
Article Editors: Stephanie Sahadeo, Victoria Huang