Researchers use sequencing to understand MERSCoV transmission

An international collaboration has used a combination of advanced genetic sequencing techniques and clinical monitoring tools to characterise the recent outbreak of the novel Middle East respiratory syndrome coronavirus (MERS-CoV) and has shown that the virus spreads between people in healthcare settings.

The collaboration, which included BRC-supported investigators, was made up of researchers from the Kingdom of Saudi Arabia, the USA, Canada and the UK.

The researchers investigated and defined the epidemiology, transmission dynamics and genetic composition of MERS-CoV from a cluster of 22 cases, following a recent outbreak in Al-Hasa in the Eastern Province of the Kingdom of Saudi Arabia. Transmission occurs within hospitals and can be rapidly fatal, the researchers reported in the New England Journal of Medicine.

Knowledge from the study about transmission enabled clinicians to minimise the spread of the infection and provide vital new information for helping to contain future outbreaks.

BRC-supported investigator Alimuddin Zumla, Professor of Infectious Diseases and International Health from UCL, said:

"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,

“The rapid pace with which the cluster outbreak at Al-Hasa was initiated by our collaboration on respiratory infections with the Saudi Arabian Ministry of Health, enabled rapid definition of the epidemiology, identification of viral genome sequences and release of them for open use on Genebank database, and bringing the outbreak under control, reflects the true collaborative spirit and value of effective international collaborations, which are essential to containing this killer virus’’.  

MERS-CoV is a new type of severe respiratory illness, similar to SARs and was first identified in September 2012. This study looked at an outbreak between 1 April and 23 May 2013 in which 15 of the 23 people diagnosed with the coronavirus infection died.

Until now, little has been known about the origin and characteristics of the new virus, but by studying the outbreak in Al-Hasa, the teams are starting to understand its transmission dynamics and clinical and genetic characteristics.

A deep sequencing technique that can rapidly sequence MERS-CoV genomes was developed by Paul Kellam, Professor of Viral Pathogenesis at UCL and a Senior Investigator at the Wellcome Trust Sanger Institute. 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.

Using this technology, the researchers confirmed that the large majority of cases (21 of 23) were acquired by person-to-person transmission in haemodialysis units, intensive care units, or in-patient units in three different healthcare facilities. Limited genetic changes were accumulated, consistent with the MERS-CoV genomes 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.

The diagnostic techniques used in this study demonstrate the importance of surveillance and infection-control in outbreaks of globally important infections. Prevention of the transmission of MERS-CoV is still a major challenge for healthcare workers and further research is needed to determine how long the virus is contagious for and to understand the complete spectrum of disease.

BRC Infection, Immunity and Inflammation (III) Programme Director Professor Deenan Pillay said: “Early and rapid identification of infectious diseases is a key priority for the BRC and investigators in this field have attracted large grants to develop molecular genetic diagnostic techniques for the rapid identification of infectious diseases from patient samples”.

Examples of these grants are recent European Commission FW7 grants: RiD-RTI (Principal Investigator: Professor Alimuddin Zumla) and PATHSEEK (Principal Investigator: Professor Judy Breuer) and UK Department of Health/ Wellcome Trust award ICONIC (Principal Investigator: Professor Deenan Pillay). In addition, early warning sensor systems are being developed as part of a major new Interdisciplinary Research Collaboration (IRC) involving BRC investigators.

Click here to read the article in the New England Journal of Medicine.