MERS-CoV Hospital Outbreak Causes Significant Morbidity

Laurie Barclay, MD

June 21, 2013

Person-to-person transmission of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) can occur in healthcare settings and cause significant morbidity, according to a case series report published online June 19 in the New England Journal of Medicine.

"In September 2012, the World Health Organization reported the first cases of pneumonia caused by [MERS-CoV]," write Abdullah Assiri, MD, from the Global Center for Mass Gatherings Medicine, Ministry of Health, Riyadh, and colleagues from the Kingdom of Saudi Arabia MERS-CoV Investigation Team.

"The natural host and reservoir of MERS-CoV remain unknown."

As reported by Medscape Medical News, 2 cases of MERS-CoV in France suggested a longer incubation period than previously thought, and a case report and phylogenetic analyses suggested important differences between MERS-CoV and severe acute respiratory syndrome (SARS) coronavirus.

In the present report, the investigators reviewed medical records for a cluster of healthcare-acquired MERS-CoV infections to extract clinical and demographic data and to identify potential contacts and exposures. They also interviewed case patients and contacts, sequenced viral RNA, and estimated the incubation period and serial interval, defined as the time between the successive onset of symptoms in a chain of transmission.

"This report clearly [shows] that infection control measurements are very critical to control the outbreak of this virus," Clemens Wendtner, MD, professor of medicine, University of Cologne, Germany, told Medscape Medical News when asked for independent comment. "This is very important in a clinical setting in order not to infect healthcare workers. But surveillance of family members and other contact persons (public transportation, etc) is of utmost importance to control the disease from a broader perspective."

Clinical Features and Transmission

In the eastern province of Saudi Arabia, 23 cases of MERS-CoV infection were reported between April 1 and May 23, 2013. At presentation, most patients had fever (n = 20; 87%), cough (n = 20; 87%), and abnormal chest radiographs (n = 20; 87%). Nearly half had shortness of breath (n = 11; 48%), and 8 (35%) had gastrointestinal symptoms.

Fatality was 65% as of June 12, for a total of 15 deaths. Six patients (26%) recovered, and 2 (9%) were still hospitalized. Median incubation period was 5.2 days (95% confidence interval [CI], 1.9 - 14.7 days), and the serial interval was 7.6 days (95% CI, 2.5 - 23.1).

Person-to-person transmission occurred in 21 of the 23 cases in hemodialysis, intensive care, or inpatient units at 3 different healthcare facilities. Sequencing data from 4 isolates demonstrated a single monophyletic clade.

Surveillance of 217 household contacts and more than 200 healthcare staff contacts revealed development of MERS-CoV infection in 5 family members (3 with laboratory-confirmed cases) and 2 healthcare workers (both with laboratory-confirmed cases).

"Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity," the study authors write. "Surveillance and infection-control measures are critical to a global public health response."

Dr. Wendtner, who also heads the Department of Hematology/Oncology, Infectious Diseases, and Tropical Medicine at Klinikum Schwabing, University of Munich, Germany, described the study strengths and limitations. "Phylogenetic analysis proved that there was a common link between these cases and also some relation to cases that have been described previously," he said. "Nevertheless the study is limited because samples (sputum, nasopharyngeal swab, blood, urine, feces, etc) were not...obtained systematically, and we do not learn how exactly the virus was spread from index cases to secondary cases. There are also other studies that prove that we have to take into account a much longer incubation time (up to 14 days)."

Clinical Implications

Dr. Wendtner, who coauthored a recent Lancet case report notes that MERS-CoV and SARS are similar, yet distinct.

Differences include the use of different receptors for entrance, different pattern of virus shedding, and presenting symptoms of severe diarrhea with SARS and severe acute respiratory symptoms with MERS-CoV.

"SARS seemed to be quite contagious, with roughly 8000 proven infected cases within a few months," Dr. Wendtner said. "For MERS-CoV, it seems that the infectivity is not as high as for SARS; after more than 1 year after the first case was diagnosed, we now have 'only' 64 proven cases. On the other hand, MERS-CoV seems to hit very heavy: once you are infected, the risk for death is quite high (fatality rate for MERS above 50%; for SARS, 10%)."

In terms of additional research, Dr. Wendtner's first priority is rigorous sampling in as many patients as possible to clarify the mechanism of transmission to other persons. He also recommends biopsy and autopsy studies to learn which organs are infected (eg, kidney failure is often observed with direct MERS-CoV infection). Research also could help discover the natural reservoir of this virus, with possibilities ranging from bats to camels or even food such as camel milk or dates.

"Finally, medical intervention in infected cases is a black box so far," he concluded. "We have to set up interventional studies in order to test whether drugs like interferon, convalescent plasma, protease inhibitors, etc are of any value for these patients."

Full conflict-of-interest information is available on the journal's Web site. Dr. Wendtner has disclosed no relevant financial relationships.

N Engl J Med. Published online June 19, 2013. Full text

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