Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection

Abstract

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging virus involved in cases and case clusters of severe acute respiratory infection in the Arabian Peninsula, Tunisia, Morocco, France, Italy, Germany, and the UK. We provide a full description of a fatal case of MERS-CoV infection and associated phylogenetic analyses.

Methods: We report data for a patient who was admitted to the Klinikum Schwabing (Munich, Germany) for severe acute respiratory infection. We did diagnostic RT-PCR and indirect immunofluorescence. From time of diagnosis, respiratory, faecal, and urine samples were obtained for virus quantification. We constructed a maximum likelihood tree of the five available complete MERS-CoV genomes.

Findings: A 73-year-old man from Abu Dhabi, United Arab Emirates, was transferred to Klinikum Schwabing on March 19, 2013, on day 11 of illness. He had been diagnosed with multiple myeloma in 2008, and had received several lines of treatment. The patient died on day 18, due to septic shock. MERS-CoV was detected in two samples of bronchoalveolar fluid. Viral loads were highest in samples from the lower respiratory tract (up to 1·2 × 10(6) copies per mL). Maximum virus concentration in urine samples was 2691 RNA copies per mL on day 13; the virus was not present in the urine after renal failure on day 14. Stool samples obtained on days 12 and 16 contained the virus, with up to 1031 RNA copies per g (close to the lowest detection limit of the assay). One of two oronasal swabs obtained on day 16 were positive, but yielded little viral RNA (5370 copies per mL). No virus was detected in blood. The full virus genome was combined with four other available full genome sequences in a maximum likelihood phylogeny, correlating branch lengths with dates of isolation. The time of the common ancestor was halfway through 2011. Addition of novel genome data from an unlinked case treated 6 months previously in Essen, Germany, showed a clustering of viruses derived from Qatar and the United Arab Emirates.

Interpretation: We have provided the first complete viral load profile in a case of MERS-CoV infection. MERS-CoV might have shedding patterns that are different from those of severe acute respiratory syndrome and so might need alternative diagnostic approaches.

Funding: European Union; German Centre for Infection Research; German Research Council; and German Ministry for Education and Research.

Figure 1

Disease and treatment (A) Chronology. Frontal (B) and horizontal (C) CT scans done on day 12 of disease, showing intense basally-pronounced congestions indicative of atypical pneumonia and acute respiratory distress syndrome. MERS-CoV=Middle East respiratory syndrome coronavirus.

Figure 2

Absolute virus concentrations in respiratory secretions and bronchoalveolar lavage samples

Figure 3

Maximum likelihood phylogenetic analysis (A) Tree with linear regression of genetic divergence from the root against time of collection of samples. (B) Tree based on all available MERS-CoV sequences (concatenated 4012 bp dataset). Full genomes for other viruses available. MERS-CoV=Middle East respiratory syndrome coronavirus.