Dr Philippa Brice, External Affairs Director for the PHG Foundation, outlines how genomic sequencing could prove to be critical in managing the spread of Covid-19.

As health systems around the world battle with the Covid-19 pandemic, genomics may seem to have little relevance. While valuable in diagnosis and care for rare disease and cancer patients, what can genomics offer front-line efforts to treat patients or control spread?

When small is beautiful

In fact, advances in genome sequencing technologies have had a huge impact on infectious disease management. The genome is the full set of blueprint instructions for living things. Understanding the human genome has important implications for health, but remains very challenging, because there is an awful lot of it: three billion characters in a coded sequence to be precise.

Viruses are tiny by contrast (the genome of the virus causing Covid-19 is 100,000 times smaller than a human genome) and so basic that they are arguably not even living, because they can exist only by hijacking the cells of other organisms – including humans. They therefore have correspondingly tiny genomes, containing instructions to make only the bare necessities for infecting their hosts and distributing lots more viruses.

Sequencing these small viral genomes is relatively quick and easy, but how does this help combat disease?

Viruses and disease

We encounter viruses all the time, and mostly our bodies fight them off with ease. We may, however, develop symptoms caused directly by the virus, such as sneezing, which can spread the virus to new hosts. We may develop symptoms caused indirectly by the virus. For example, we might develop a temperature, which is an example of our own immune responses to the virus. Sometimes these symptoms can be life threatening.

The more often we encounter a virus, the better our bodies are at recognising and destroying it. Vaccination provides an artificial exposure to a key element of a virus that primes us to respond swiftly and effectively against later true encounters. However, some viral genomes are good at changing slightly over time, which helps them to gradually escape this immune recognition.

A new virus, such as the one causing Covid-19 presents a particular threat: our bodies don’t easily recognise and repel it. Combined with the fact it is very infectious, it has allowed rapid spread to pandemic proportions. Our ability to sequence viral genomes gives us an opportunity to respond quickly.

Using genomics to fight viruses

The UK is a global leader in viral genome sequencing, which is used by both local clinical microbiology services and national Public Health England laboratories to detect, monitor and control viral disease. Genomics is normally used to identify the source of usual disease outbreaks by comparing viral genomes from different patients, other contacts and environmental samples, to inform proper infection control measures.

In a larger outbreak, this is more difficult because of the greater number of patients and complexity of interactions, but it informs modelling that can help map and ultimately predict patterns of spread and opportunities for intervention. Genome-based diagnostics offer much faster and sensitive identification of infections than traditional microbiological methods. Portable miniature sequencers are proving invaluable for real-time analysis of viral genomes in the community, for example, during the 2014 Ebola and 2015 Zika outbreaks.

Genomics can help vaccine design. Just consider how the influenza virus, which notoriously causes annual epidemics, as well as occasional pandemics such as the 2009 H1N1 swine flu, does so because it is especially good at changing its genome. Around the world, scientists monitor and analyse flu genomes to inform the design of the annual vaccine and to optimise it to fight the most common forms of flu virus circulating that year.

Genomics and Covid-19

The current pandemic is caused by another virus, the coronavirus family, which can affect animals as well as humans. It has been under scrutiny for many years because coronaviruses from animals have given rise to other serious new human diseases. The 2003 SARS (severe acute respiratory syndrome) outbreak was traced back to a Chinese bat coronavirus, whilst dromedary camels were found to be involved in the 2012 MERS (Middle East respiratory syndrome) outbreak.

Chinese scientists were quick to assess viral genome sequences from the earliest patients in Wuhan in late 2019, and compare it with known coronaviruses, allowing them to identify it as a new human virus SARS-CoV-2, likely to have emerged from a single bat coronavirus transmission to a human. As the virus spreads, evidence from other countries continues to show strong similarity between viral genomes, which is good news: SARS-CoV-2 does not appear to be changing rapidly, and therefore a vaccine designed against it has a good chance of being effective.

Looking ahead

Now a new COVID-19 Genomics UK Consortium has been launched, bringing together expertise from NHS England, Public Health England and other research centres. They will sequence the SARS-CoV-2 virus from infected people, with and without symptoms, to understand exactly how it is spreading. They will also look at infection hot spots, in order to inform public health interventions, as well as studying how the virus might change over time in order to inform medical responses. Potential treatments already being trialled were identified by selecting medicines known to be effective against similar viruses, based on viral genome comparisons. A trial vaccine in development in Norway, based on genomic insights, could be ready in as little as six months, which would be a record speed.

Viral genome sequencing may provide clues as to why different people respond very differently to infection, which could be important for clinical care and for more accurate identification and protection of those at greatest risk of severe disease. However, unravelling this issue is likely to be a greater challenge, as it probably relates more to variation between human genomes.

The UK is uniquely well-placed to capitalise on strengths in genome sequencing and analysis alongside national systems for healthcare and data sharing to lead in developing effective short and long-term strategies against Covid-19. Scientists will also be looking to learn all they can not only about this virus, but about how to prepare for future infectious disease threats. Genomics will undoubtedly remain a critical element for response.

Latest updates on the Covid-19 spread across the UK can be found here.