Combination of genetic and clinical tools maps recent coronavirus outbreak

An international study involving scientists at the Wellcome Trust Sanger Institute has characterised the recent outbreak of the novel Middle East respiratory syndrome coronavirus using a combination of advanced genetic sequencing techniques and clinical monitoring tools.

Teams from the Kingdom of Saudi Arabia, the USA, Canada and the UK have shown that the virus spreads between people in healthcare settings, including hospitals, and can be rapidly fatal.

In this outbreak, 15 of the 23 people diagnosed with the coronavirus infection have died, corresponding to 65 per cent. Until now, little has been known about the origin and characteristics of the new virus, but by studying an outbreak in the eastern Saudi Arabian province of Al-Hasa, the teams are starting to understand its transmission dynamics and clinical and genetic characteristics.

Sanger Institute researchers have developed a deep sequencing technique that can rapidly sequence Middle East respiratory syndrome (MERS) coronavirus genomes. This technique uses the minuscule levels of viral genetic material present in patients' clinical samples to diagnose the infection; when used with bespoke computer programs, the process reduces the time of genome analysis from weeks to days.

Professor Paul Kellam from the Wellcome Trust Sanger Institute said: "We developed our rapid, deep and whole-genome sequencing of MERS coronavirus to understand more about the genetics of this virus, and for the method to be used in any new outbreaks. This is exactly what we have been able to achieve."

Using this technology, the researchers confirmed that the virus was being transmitted from person to person and that it accumulated limited genetic changes consistent with it replicating within one patient and then transferring to the next.

Further analysis revealed that all the coronaviruses in the outbreak came from a common ancestor that appeared between February and April 2013. These discoveries confirmed the observations of hospital staff tracking the transmission of the virus.

"By analysing the complete genomes of four MERS-coronavirus-positive samples, we found that the viruses were closely related to one another genetically – indicating that they are part of the same infection outbreak," said Dr Abdullah Al-Rabeeah, Minister of Health, Kingdom of Saudi Arabia. "The low level of sequence divergence of the virus within the Al-Hasa cluster is in concordance with the hospital epidemiological investigation, suggesting that transmission took place within this group of patients and healthcare workers."

Using this knowledge, clinicians have been able to minimise the spread of the infection and provide vital new information for helping to contain future outbreaks.

"The fact that the hospital outbreak was contained effectively and there were no more new cases reported shows that preventive infection control measures are crucial to prevent spread of the virus," said Professor Alimuddin Zumla of UCL.

Prevention of the transmission of MERS coronavirus is still a major challenge for healthcare workers. Further research is needed to determine how long the virus is contagious for and understand the complete spectrum of disease, to help healthcare workers develop and implement new strategies to tackle this growing issue.

Professor Ziad Memish, Deputy Minister of Health, Riyadh, Kingdom of Saudi Arabia, said: "While there remain many unknowns about this new lethal virus, the Saudi Ministry of Health is committed to continue its collaborative work with all national and international experts under the umbrella of the World Health Organization to unravel the mysteries of this novel virus."