Reply to Leow.

To The Editor—We thank Leow for his correspondence [1] in which he recognized the significance of our recent work [2]. We also welcome the constructive comments he provided concerning the limitations of our study. In our study, we focused on the in vitro cell line susceptibility of the novel coronavirus, now renamed “Middle East respiratory syndrome coronavirus” (MERS-CoV) [3]. We agree with Leow that the results from studies of in vitro cell line tropism may not directly correlate with the in vivo behavior of the virus. Our observation that MERS-CoV replicates more efficiently than does SARS-CoV within in vitro human tissues is supported by the findings in subsequent ex vivo culture systems that showed that MERS-CoV productively replicates in both human bronchial and lung tissues, as compared with severe acute respiratory syndrome (SARS)-CoV, which only replicates in lung tissues [4]. Furthermore, an animal model using rhesus macaques for MERS-CoV infection was recently developed and showed histopathological evidence of acute localized to widespread lung consolidation in all infected animals, resulting in clinical disease [5]. Detailed histopathological examination of patients with MERS-CoV infection would be important for the confirmation of these changes in humans.

Although dysfunction of the hypothalamus–pituitary­–adrenal axis has not been well described in patients with MERS-CoV, some patients did develop hyponatremia, which was possibly related to a syndrome of inappropriate antidiuretic hormone secretion [3]. We agree that further studies on the predilection of the virus for endocrine tissues might be important to our understanding of the pathogenesis of this highly fatal disease and optimization of treatment strategies. In particular, the therapeutic roles or potential detrimental effects of systemic corticosteroids, which were used empirically in the early disease stages in some of the patients with MERS-CoV infection, remain unclear [3].

Since the publication of our article, the MERS-CoV epidemic has continued to evolve without obvious signs of being completely controlled. The total number of laboratory-confirmed cases in 10 countries over 3 continents has increased to 90 with 45 fatalities as of 21 July 2013. Although an animal reservoir of MERS-CoV has been suggested [6-8], the definitive source has so far not been identified. The epidemiological emergency posted by the evolving outbreak also calls for the development of effective antiviral treatment. In addition to supportive treatment such as extracorporeal membrane oxygenation and renal replacement therapy, combinational ribavirin and interferon-α2b has recently been shown to exhibit in vitro anti-MERS-CoV activity [9]. The efficacies of other potential therapeutic strategies including interferons, antiviral peptides targeting the heptad repeat 2 region of the MERS-CoV Spike (S) protein, and S1 domain-dipeptidyl peptidase 4 interface inhibitors should be determined in further laboratory and clinical studies [3, 10].