From mutations to cat infections: Four ways genomic surveillance has helped us understand Covid-19 virus

Genomic surveillance is helping health authorities to understand local outbreaks and monitor changes in the Covid-19 virus.

The Covid-19 Genomics UK (COG-UK) Consortium - led by the Wellcome Sanger Institute at Hinxton and the University of Cambridge - has just been awarded a further £12.2million to expand its work.

Here are four ways it has helped us better understand SARS-CoV-2.

1 Improving infection control

At Cambridge University Hospitals NHS Foundation Trust, six patients with end-stage kidney failure - spread across locations including the emergency departments and an acute admissions ward - were diagnosed with Covid-19 between April 1-20.

Sequencing carried out on their samples found they were identical at a genomic level, suggesting a common source of infection.

Epidemiological investigation showed that all six patients underwent treatment at the same outpatient renal dialysis unit on the same days of the week.

The findings led to a review of infection control measures, identifying shared patient transportation and neighbouring dialysis chairs as risk factors.

Universal mask use for patients and staff was introduced, the waiting room area was closed and social distancing improved.

Genomics also helped rule out linked transmissions to other renal patients, after showing their virus was from a different lineage.

2 Exploring mutations

Genetic changes accumulate in viruses as they replicate and are transmitted.

COG-UK researchers have assessed all mutations in the Covid-19 virus’ spike protein, which it uses to enter human cells.

The location of this protein on the surface of the cell could affect a person’s immune response and it is also the target for many therapies and vaccines being developed.

One notable mutation that causes a change to spike protein is termed N439K.

Research has shown that a virus with this mutation is able to resist monoclonal antibodies, such as those being trialled as treatments, and still bind to its target on human cells.

However, vaccines will prompt the immune system to make a range of antibodies, meaning that even if the spike protein can resist one, it is likely another will be able to neutralise the virus.

The COG-UK researchers have stressed the importance of systematically monitoring spike protein mutations, particularly in the run up to a vaccine being introduced.

Once vaccinations are scaled, the spike protein will be under ‘selective pressure’. Those viruses with certain mutations could fare better under a vaccine-primed immune response than others.

“Whilst limited genomic diversity has emerged to date, this may change in the next phase of the epidemic as selective pressures exerted by vaccines, treatments and non-pharmaceutical interventions increases,” COG-UK researchers note.

COG-UK has set up a group and systems dedicated to monitoring new and existing mutations, prioritising those that need in-depth analyses.

3 Understanding local outbreaks

As of last month, COG-UK data and tools have been used in more than 120 SARS-CoV-2 outbreak investigations in the UK.

Researchers led by Dr Andrew Page at the Quadram Institute in Norwich used genome sequence data and clinical information to understand the spread of the virus in the region, confirming an outbreak at a food processing facility and ruling out a hospital setting as the source of another outbreak.

They also found 16 viral variants, or lineages, in health care workers that were not present in patients. This helped to show that PPE and infection control measures are effective in stopping transmission of the virus.

4 Studying human-to-cat transmission

Professor Margaret Hosie at the University of Glasgow and colleagues, who are part of the COG-UK team, demonstrated transmission of the SARS-CoV-2 virus between humans and cats.

Two cats from different Covid-19 infected households were shown to be infected with the virus from humans. One cat had to be put down and the findings have implications for how those with Covid-19 interact with their pets.

Currently, there is no evidence of cat-to-human transmission, or that any domestic animals play a role in the epidemiology of human infections with SARS-CoV-2, but Prof Hosie notes that ongoing studies are required.

“It will be important to investigate whether cat-to-human transmission is possible or likely, and to determine the duration of virus shedding and the level of contact with humans that is required for transmission to occur,” the paper, published in biorXiv in September, notes.

It adds: “Our findings highlight the importance of co-ordinating the testing of humans and animals within affected households to monitor zoonotic transmission,”

Ferrets and hamsters are susceptible to the virus, but ducks, chickens and pigs appear not to be.

Who are COG-UK?

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£12.2m funding will help Cambridge-led COG-UK expand Covid-19 genomic surveillance