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1、editorials n engl j med 369;5 nejm.org august 1, 2013 466 The new england journal of medicine Person-to-Person Spread of the MERS Coronavirus An Evolving Picture Stanley Perlman, M.D., Ph.D., and Paul B. McCray, Jr., M.D. Approximately 1 year ago, a novel coronavirus, the Middle East respiratory syn
2、drome coronavirus (MERS-CoV), was first identified in the Journal as the causative agent of a lethal pneumonia in sev- eral patients in the Middle East.1 As of July 10, 2013, a total of 80 cases have been identified in the Middle East (Saudi Arabia, Jordan, Qatar, and the United Arab Emirates), Euro
3、pe (United King- dom, France, Italy, and Germany), and North Africa (Tunisia), with a case fatality rate of 56%. Since this coronavirus is a close relative of the virus that caused the severe acute respiratory syndrome (SARS), a short-lived but alarming epidemic in 20022003 that resulted in approxi-
4、 mately 8000 cases and 800 deaths, governmental, public health, clinical, and laboratory authorities all mobilized rapidly to respond to the new virus outbreak. Soon after the identification of MERS- CoV, information about its genomic sequence and organization, species tropism, and host-cell re- cep
5、tor (dipeptidyl peptidase 4) was published.2,3 These initial studies did not identify the source of this newly identified virus, nor did they reveal whether MERS-CoV could be transmitted from human to human, a requirement for designation as an epidemic disease. In this issue of the Journal, Assiri e
6、t al.4 de- scribe the largest outbreak of MERS-CoV infec- tion thus far, showing that the virus is trans- mitted from human to human. This outbreak occurred in several hospitals in the governorate of Al-Hasa in eastern Saudi Arabia, with trans- mission probably occurring in dialysis units, in- tensi
7、ve care units, and wards. Most patients had underlying diseases, with a remarkable number (17 of 23) having diabetes. In addition to show- ing that human-to-human transmission oc- curred frequently, the relatively large number of patients infected in this outbreak made it possi- ble to define charac
8、teristics of the infection, such as the incubation time (5.2 days) and the serial interval (7.6 days). As seen in the SARS epidemic, there was variability in the numbers of patients infected by each index patient, with 1 patient transmitting virus to 7 contacts; super- spreading events, in which a f
9、ew patients infect- ed large numbers of contacts, were critical fac- tors in SARS reaching epidemic proportions. The study by Assiri et al. shows that MERS-CoV has the potential to spread widely within health care settings, infecting primarily other patients but also health care workers and family c
10、on- tacts, although to a lesser extent. Patients with diabetes or chronic renal failure appear to be at especially high risk for severe MERS-CoV infec- tion, but whether these coexisting conditions represent true risk factors or whether these pa- tients happened to be preferentially exposed to index
11、 cases is not known, given the relatively small number of infected patients. Also unclear from this study is the extent to which MERS- CoV infection is a systemic disease. Acute renal failure developed in several patients with the in- fection,1,5-7 possibly reflecting a high level of di- peptidyl pe
12、ptidase 4receptor expression in the kidney. However, in the absence of tissue sam- ples obtained at surgery or autopsy, it has been difficult to determine the extent to which kid- neys or other organs are infected. Although the report by Assiri et al., as well The New England Journal of Medicine Dow
13、nloaded from nejm.org at UNIVERSITY OF OTAGO on July 21, 2015. For personal use only. No other uses without permission. Copyright 2013 Massachusetts Medical Society. All rights reserved. editorials n engl j med 369;5 nejm.org august 1, 2013 467 as others in the Journal and elsewhere,6,7 indi- cates
14、that human-to-human transmission occurs, at least in the context of close contact, many ad- ditional questions related to the transmission of MERS-CoV and its ability to reach epidemic pro- portions are unanswered. On one hand, corona- viruses are notorious for rapid adaptation to new hosts,8 a find
15、ing that is best illustrated by the ability of SARS-CoV to adapt to replication in the human lung. Adaptation involved changes in the surface glycoprotein, which is responsible for binding to the host-cell entry receptor, and in proteins involved in viral replication.9 Addi- tional adaptation of MER
16、S-CoV to human popu- lations, although not observed thus far, is likely to occur and would augment the possibility of widespread infection. Furthermore, the commu- nity (probably zoonotic) source for MERS-CoV remains unknown, making it difficult to know whether periodic reintroduction into human populations will occur and contribute to the po- tential for human adaptation. Moreover, the rel- ative importance of aerosol transmission versus spread by large droplets or contact is unknown, b
