MERS-CoV Coronavirus Not So Much Like SARS After All

Laurie Barclay, MD

June 17, 2013

Middle East respiratory syndrome coronavirus (MERS-CoV) infection has shedding patterns different from those of severe acute respiratory syndrome (SARS) coronavirus and therefore may need alternative diagnostic tests, according to a case report and phylogenetic analyses published online June 17 in Lancet Infectious Diseases.

"Laboratory data like these are critical to reach recommendations for diagnostics, to make projections about the prognosis of the patient, as well as to estimate infection risks," first author Professor Christian Drosten, MD, from the Institute of Virology, University of Bonn Medical Centre, Germany, said in a journal news release.

"In the absence of qualitative laboratory data from well-documented MERS cases, most of these considerations were up to now made upon an assumed analogy to SARS. However, we're now finding that certain elementary traits of the MERS virus appear to be different to SARS."

MERS-CoV is responsible for case clusters of often fatal, severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the United Kingdom.

The patient described in this report was a 73-year-old man from Abu Dhabi, United Arab Emirates, who had been treated for multiple myeloma 5 years previously. Two days after developing influenza-like symptoms, he developed pneumonia that was treated with antibiotics and artificial ventilation. On day 11, he was transferred to the Klinikum Schwabing in Munich, Germany. The patient died on day 18 from septic shock.

Reverse-transcription polymerase chain reaction and indirect immunofluorescence detected MERS-CoV in 2 bronchoalveolar fluid samples, with highest viral loads in the lower respiratory tract (up to 1.2 × 106 copies/mL). In urine samples, maximum virus concentration was 2691 RNA copies/mL on day 13, but on day 14, the patient was in renal failure without detectable virus in the urine. The contribution to renal failure of previously prescribed antibiotics was unclear.

On days 12 and 16, stool samples contained up to 1031 RNA copies/g MERS-CoV (close to the lowest detection limit), whereas SARS is typically present in high concentrations in stool. On day 16, 1 of 2 oronasal swabs was positive but contained only 5370 copies/mL viral RNA. Blood tested negative for MERS-CoV.

Genetic Analysis and Clinical Implications

The investigators analyzed the full virus genome along with 4 other available complete MERS-CoV genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation, and determined that the time of the common ancestor was midway through 2011.

By adding novel genome data from an unlinked case treated 6 months earlier in Essen, Germany, the investigators demonstrated a clustering of viruses derived from Qatar and United Arab Emirates.

"With only five complete genome sequences so far available there is an urgent need for more genetic data to reveal the spatial and temporal distribution of these cases, estimate the number of independent human chains of transmission, and thus better evaluate the threat this virus poses to world health," coauthor Professor Clemens-Martin Wendtner, MD, from the Klinikum Schwabing, Munich, said in the news release.

In an accompanying comment, Professor Benoit Guery, PhD, from Hopital Huriez in Lille, France, and Sylvie van der Werf, PhD, from Institut Pasteur in Paris, France, describe the epidemiology of SARS and MERS-CoV.

"[T]he observation of a worsening of respiratory status, from influenza-like symptoms to pneumonia and then acute respiratory distress syndrome, hints at a potential window for treatment," they write. "SARS treatment protocols could be used, but the major differences in host responses and susceptibility to drugs such as interferon-alfa for these two coronaviruses should be kept in mind. Interferon with or without ribavirin is a promising candidate treatment."

The European Union, German Centre for Infection Research, German Research Council, and German Ministry for Education and Research funded this study. The study authors and editorialists have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online June 17, 2013. Article abstract, Editorial extract

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